Red Blood Cells | RBC | Erythrocytes | Erythropoiesis🩸

now we are going to talk about red blood cells right which are also called erythrocytes some students know that red blood cells are called erythrocytes that's a great news so let's know try to know something more than that that red blood cells first of all they primarily are formed in the bone marrow actually in prenatal development hematopoiesis is in the yox and then in the liver and supplement so before the birth red blood cells are first of all being formed in the jock sack then hamato as her metal poses shift to the liver and shift to the spleen so red blood cells erythropoiesis occur in the liver in supplement and then a shift to the bone marrow in a new bar all the erythropoiesis is going on in bone marrow right so let's see in the bone marrow what are the different stages of development of red blood cells let's suppose here is your bone marrow house and here is your yes circulation now in the bone marrow cells the very first cell which is responsible for hemopoisis is yes pluripotent stem cell right pluripotent stem cell and this divides into two types of cells yes please lymphatic stem cell lymphoid stem cell and yes myeloid stem cell right then myeloid stem cell can be divided it can divide into yes what type of cells three types of cells colony forming unit erythrite megakerioide then colony forming unit okay rather mainly into two colony forming unit yes g e okay colony forming unit gm granulocyte and monocyte right and from this erythrite right it divides into two right column forming unit which goes in formation of megakaryo poises megacardioposis mean formation of platelets formation of platelets and other cell is colony forming unit yes colony forming unit erythroid this is a happy cell we are going to derive rbcs right again this is a cell will concentrate right which is the progeny of the cell or derivative of this cell will eventually become red blood cells right but from where the cell is coming let's go back the pluripotent stem cell divide into lymphoid stem cell and myelitis stem cell myelite stem cell can give rise to colony forming unit erythrite megacarriad cell and this thread mega kg itself can make two colonies that is colony forming unit thread and colony forming unit megacardioid and of course colony forming unit electrode uh will make the cells which will become red blood cells and colony forming unit megacardioid will eventually make platelets right we will concentrate on this right uh if we really concentrate on that i need more space to explain it well so let's make the yes boner house bigger look this colony forming unit erythroid right this is a large cell about 20 micron the first recognizable cell which is formed from here is pro erythroblast what is it pro erythroblast now prove through blast goes into derivative cells and progressively cells get smaller this is a very important concept that when proestroblast is going differentiating into more mature cells the derivative cells are progressively getting smaller right let me tell you this is which cells pro erythro blast blast mean rapidly proliferating cell pro rethroblast then these three next stages are erythroblast these three are yes erythro blast it means they are rather erythroblast next is also erythro blast and then there is erythrocyte erythro site blast then there is erythroblast and this erythroblast which is the first one this is called vasophilic erythroblast because it takes blue strain basophilic erythroblast then next take some blue color and some red color so we call it polychromatic what we call it poley polychromatic right polychromatic erythroblast and after that this one is very much red so this is called orthochromatic ortho chromatic of course this is also so chromatic or rather make it through last now one thing which is important that during the maturation of this process of erythropoiesis the earlier cell is prorethroblast which is going to what is this mesophilic erythroblast then it goes to polychromatic erythroblast then it go to orthochromatic erythroblast rather because it does not multiply so we can call it orthochromatic normoblast orthochromatic normal please correct it carbon normal blast normocyte because it does not multiply sorry normal site now let me tell you about their nuclear situation what really happens that in the pro-thro arthroblast nucleus is very large it has very very fine chromatin it has very very fine chromatin and it has prominent nuclear lie right and cytoplasm is basophilic blue it is basophilic now let me tell you why it is so you know chromatin is here fine chromatin fine chromatin mean it is you chromatin you chromatin mean lose chromatin the chromatin in the nucleus may be condensed or it may be loose condensed chromatin is called heterochromatin and loose chromatin is called zeu chromatin actually whenever cells are multiplying they open their dna and they are making replication of dna so whenever cell has to multiply or proliferate it has to do replication of dna and whenever it has to do replication of dna then it has to open up its dna and open up its chromatin so chromatin will convert into which type you chromatin because these cells multiply a lot erythroblast right so they have to have an open nucleus open nucleus mean nucleus with loose chromatin nucleus with your chromatin is that clear secondly they are having very prominent nucleoli you know nucleoli are the factories to produce ribosomes these are the places in the nucleus where ribosomes are assembled and then ribosomes go to the cytoplasm because these cells in the future have to make lot of proteins like hemoglobin right so for synthesis of protein they need ribosomes so because the cell has to multiply a lot so it is keeping your chromatin large nucleus open nucleus with loose chromatin and because it is going to make a lot of proteins like hemoglobin so it has to synthesize a lot of proteins synthesizing machinery like ribosomes and ribosomes are assembled in nucleoli so these cells have large nucleus open nucleus with prominent nuclei is that right and because yet there is no hemoglobin but some ribosomes are present over there and messenger iron is present over there so the cytoplasm takes blue color why the ribosomes take blue color because ribosomes have also rna ribosomal rna right so dna and rna take blue color they take basic dyes is that right so whenever cytoplasm is rich in messenger rna or rich in ribosome cytoplasm will be which colored blue colored right now what really happens when erythroblast is stimulated it proliferates and it gives rise to lot of bits of basophilic erythroblast right basophilic resistor why we call this basophilic because here they have produced lot of ribosomes and because they have a lot of ribosomes so cytoplasm become really intensely below is that right but nucleus become smaller nucleus become smaller and it has you chromatin in the center and it may have a little bit heterochromatin or condensed chromatin is that right now look as early cells or precursor cells are going to more mature cells right the system should have three types of maturation there are three steps of maturation there should be size maturation maturation in size there should be maturation of nuclear material nuclear maturation and there should be cytoplasmic maturation cytoplasmic maturation listen size maturation mean that as you're moving from early cells to more differentiated cells in in the process of erythropoiesis size should become progressively smaller that is size maturation nuclear maturation early cells the proliferating more later cells are not proliferating at all and eventually erythrocyte is without any nucleus it means that early cells which are proliferating they should have open nucleus open nucleus mean nucleus with zero chromatin as you move forward replication capacity is becoming less proliferation capacity is becoming less so open chromatin will go to condensed chromatin so you chromatin will start converting into heterochromatin right and eventually because the finished product rbc does not have any nucleus it means nucleus should come out again it means during the erythropoietic process from precursor cells to the finished product rbcs nucleus should progressively condense and then go out of the cell is that right so initially nucleus is open then some heterochromatin then nucleus at this stage become more what is this dense more condensed and here nucleus becomes very very condensed and it is about to leave is that it so this process is called nuclear maturation third concept is cytoplasmic maturation in the early cell hemoglobin is not there in the early cells hemoglobin is yet not synthesized but because cell intends to make lot of hemoglobin so it has to make a lot of enzymes and lot of globin chains so it means that this cell has a plan to make lot of proteins to make a lot of proteins it has to synthesize lot of ribosomes and messenger rna and these ribosomes and messenger rna impart blue color to the cytoplasm that is why early cells have visophilic cytoplasm or blue cytoplasm but as seldom maturing their cytoplasm gradually and progressively hemoglobin will appear in the cytoplasm at this stage hemoglobin appear so some areas of cytoplasm become hemoglobin is and these areas are called these look acetophelic or asthenophilic and those areas where yet there is abundant what is there ribosomes and now at this stage in polychromatic cells cytoplasm has blue shade as well as pink shade why because blue shade in those areas of the cytoplasm which are very rich in ribosomes and messenger rna you know when one messenger rna has a lot of ribosome whole complex is called poly ribosomes so actually this blue colors are due to poly ribosomes and this uh red shade is coming due to presence of abundant hemoglobin so this type of shell will a cell will give double shade in some areas it will be strained bluish in other areas cytoplasm will be strained red you have seen checkers bored what are the colors used there black and white are black and red checkers okay you can say this is a checkerboard with blue and red now so because it is double color we call it polychromatic cells what is this erythroblast which is polychromatic precursor to this was not having hemoglobin so it was purely blue so it was basophilic but when you go to the next stage now basophilia is significantly reduced and cytoplasm is really too much mature and it means too much mature mean it is having a lot of hemoglobinization and basophilia is far less right so when it is heavily hemoglobinized right we call it orthochromatic what is the color called ortho chromatic right so what we have learned during this process that the first recognizable precursor cell is first recognizable precursor cell of arithmetic processes called pro erythro blast it's a large cell with the open nucleus multiple nucleoli right and visophilic cytoplasm right it is about 20 micron the next stage is usually 17 micron then 14 micron then 10 micron and so and so forth in the end you have rbc which is 7 to 8 micron progressively cell is size is reducing so pro ortho blast is large open nucleus multiple nucleoli and visophilic cytoplasm it multiplies into many basophilic erythroblast and this is basophilic erythroblast a result of the mitotic dependence of prorethroblast right uh and these are having a nucleus which is smaller in size some heterochromatin appears it means some chromatin is undergoing condensation now right and it means nuclear maturation has started and cytoplasm even becomes more basophilic because the cell has now accumulated lot of ribosomes and messenger rna or polyribosomes am i clear then we go to the next stage and the next stage is called yes polychromos chromatic erythroblast and this polychromatic erythroblast why we call it polychromatic again first you have to see maturation in size maturation in nucleus and maturation in cytoplasm maturation size size is now further reduced we started with 20 micron 17 micron maybe this is just 13 14 micron number two nuclear maturation now nucleus is more condensed right and more heterochromatin is there and nuclei of course disappear now because cell is no more synthesizing any more ribosomes it had enough ribosomes and uh there's evidence of fully formed what is this hemoglobin which is imparting which color red color so blue and red shades double shades are coming when you strain their cytoplasm and these cells are called polychromatic yes erythro blast right after that in the next stage what really happens that nucleus further mature and become very condensed you see it's very very condensed nucleus and it is about to be expelled from the cell is that right now this cell which is having a very very mature nucleus it has very heavy hemoglobinization so due to that reason vasophilia become very less and there is dominant asynophilic cytoplasm there is dominantly sinophilic cytoplasm reddish color or pinkish color cytoplasm pinkish thing remind me something i don't know it's not relevant with the lecture but it just reminds me something you see a man went to see a very big boss of a ceo of a fortune 500 company right and that man who was a visitor uh he was stopped by the secretary secretary said that you cannot go in my boss is talking to his girlfriend and i cannot interrupt so what happened the visitor keep on sitting for one hour then he said please check the secretary again look through the glass she says still you cannot talk to my boss now he is talking to his wife visitor got really very angry he said how did you know sitting here just trying to fool me you didn't talk to him you don't tell up on him and fooling me that now he's talking to girlfriend now talking to wife how you know it she says there two ways one reason is when he is talking to his girlfriend he's holding the telephone like this and when he's talking to wife telephone goes like that right and sometimes it goes like this second reason when he's talking to his girlfriend boss looks pinkish right he must be orthochromatic boss pinkish but when he was talking to his wife he become bluish not only pankish you become bluish probably he cannot breathe well and cyan was his appears and sometimes wife if talk goes along with the wife he walk in the office like sheepish like a sheep right so she told the visitor that you cannot under both circumstances you cannot talk to the boss right so as a good secretary knows by looking at the face of the boss right when his pancation when it is bluish and what is the cause a good doctor should know when you look at the bone marrow slide right that if these are pinkish cells in the rethor poses a bluish cell in the erythropoiesis what is really happening there if you are having basophilic erythroblast it is having more ribosomes more messenger rna and ribosomal rna and yet not and yet not having hemoglobin but if you are having fully ortho chromatic cell or highly acinophilic precursor cell right then it is heavily hemoglobinized it is towards more maturity and of course in between there there's a stage of polychromasia now i want to clear some confusion these three cell stage have different nomenclature in different books some books say this is every book called this cell prorethroblast every author call this prorthroglass thank god from where they agree after that the confusion start let's try to manage that confusion one way is to call us all these cells normal blast early normoblast okay let me put it early normal early normoblast intermediate normal blast and late normal site normal site right early mean mesophyllic intermediate means double color right polychromatic and late mean heavily hemoglobin is reddish that's the right of course it is in early development and that is in late development so this is one way to call it all of them are supposed normoblast early normoblast intermediate normoblast late normal blast or preferably normocyte why this confusion that in many books write it as blasphemy usually does not undergo mitosis that is why i write blast because book riot blast but actually it is not blast because it does not proliferate it is about to lose its nucleus and anyone who loses the nucleus is not going to proliferate am i clear so one nomenclature is early intermediate and late normal blast but late normal blast should be called normal site number two all of them can be called erythroblast right but basophilic erythroblast then polychromatic erythroblast then orthochromatic erythroblast but actually it should not be blast because it does not multiply am i clear but they call it blast right i don't know what to do with them erythro blast but it is ortho chromatic is that clear then we go to the next stage next stage nucleus has gone out and who will eat eat it up this nucleus macrophage is present in the bone marrow they'll have to eat anything they find including the nucleus of other cells right so what is left behind look at it the left behind is the cell which is heavily hemoglobinized with a little blue network a little blue network now this type of cell is called cell with a network network is called retic so this is a cell with a network we call it reticulocyte what we call it reticulocyte and this reticulocyte is a fresh blood cells which appears in circulation reticulocyte is a fresh rbc which appear into circulation but this reticulocyte is having some very little mesophilia which are the remnant ribosomes right with little messenger rna and ribosomal rna this is a reticulocyte within one two days with further maturation what will happen that it's of course size will become a little more smaller and retic will disappear it means ribosomes will disappear and hemoglobin formation will stop and cell will become purely hemoglobinized and now it is called mature erythrocyte now it is called mature erythrocyte what is it reticulo site normally in our blood reticulocytes are one to two percent of rbcs right if your bone marrow is working with the normal speed if your bone marrow is producing erythropoiesis with normal way then reticulocytes should be one to two percent of your is that right but if in your blood blood you find reticulocytes are more than suppose 10 percent this heavy reticulocytosis it means bone marrow is under working or overworking bone marrow is overworking and there is fast what radical there is fast erythropoietic process so actually this reticulocytes percentage in the blood is very important for the doctors when laboratory gives a report reticulocytosis is suppose two percent it is normal but if you see in the report comes patient has reticulocytosis reticulocytes with 20 percent it means there is a very heavy reticulocytosis it means in this spatial person's blood there is a fresh rbc's are coming from the bone marrow very very rapidly and there is accelerated erythropoiesis opposite to that if you find someone blood you take a sample and you're studying there's no reticulocyte it means the restore process has stopped this type of problem occur in some aplastic anemias where immune immune system attacked the stem cells and if stem cells are destroyed the fresh products are not made and there will be no reticulocytes in the blood so in a way reticulocytes are index of erythropoietic process is there any question there's no question at all so this was something about erythropoiesis now after this we come to the characteristics of rbc's in the blood a total asylum process takes about one week and this is under strong influence of erythropoietin right erythropoietin is a glycoprotein which comes from the kidney to the blood and then to the bone marrow you know from the kidney erythropoietin is released erythropoietin and erythropoietin goes to the bone marrow house and it is responsible to stimulate the colony farming unit and produce more pro-orthoblast and so that protheroblast eventually convert into more rbcs is that right so rethrow potion drives the erythropoietin drives the erythropoietic process but in the kidney exactly in which area erythropoietin is produced in the kidney there are special tubes which are called yes nephron around these tubes there are special capillaries these capillaries are called parry tubular capillaries what are these capabilities called parry tubular capillaries actually the endothelial cells endothelial cells endothelial cells of peritubular capillaries have a capability to sense the oxygen and the blood if partial pressure of oxygen in the blood is very low and these endothelial cells are not getting getting enough oxygen they start synthesizing and releasing erythropoietin so that erythropoietin go to the bone marrow right and as the erythropoiesis is accelerated and more rbc's come into blood and oxygen carrying capacity of blood is increased oxygen carrying capacity of the blood is increased am i clear right now after the erythropoiesis now we come to the some basic characteristics of rbcs rbc is basic characteristics of the rbc is what is the size of an rbc who will tell me suppose this is a section of an rbc right the hole diameter let's suppose here it is seven to eight just you're right micrometer right but as the edge it is about 2.5 micron and in the center it is about one micron right and rbc mainly consists of membrane cell membrane and having some proteins which are associated with the membranes and lot of hemoglobin inside is that right so first i will talk about membrane characteristics as compared about compared to the content of the rbc rbc has extra membrane advantage of extra membrane is that it is biconcave desk so surface areas more so that hemoglobin can exchange the gases easily am i clear number two advantage of having extra surface area not only facilitate the gas exchange or oxygen uptake and release it also facilitate the folding of the rbcs when rbc's have to pass through very narrow capillaries they can they are very flexible and they can fold on themselves and squeeze through narrow areas is that right now let me talk about the membrane of the rbcs like all other cells membrane of the rbc is lipid bilayer it is lipid bilayer but there is some very special characteristics of rbc's membrane right what is that that there are certain proteins which are called integrin sorry these proteins are called integral proteins which are through the membrane and the other proteins which are within what is this within the structure of are under the surface of interior surface of the rbc membrane and these proteins are called peripheral proteins these proteins make a network and this network is held and attached with what are these membrane proteins now this network of proteins which is present inside you can say it's a network like this what is the purpose of this network anyone who knows what is the purpose of this net network of proteins there's a network of proteins to the inner side of the rbc membranes and this network is connected with the membrane through multiple proteins okay let me tell you if let me give you an example that what is the real purpose of this listen rpcs have extra membrane is that right so it is just like that that a cell with less cytoplasm and more membrane it is just like that that if you are having small size your own size is small and you are having a dress which is very big it reminds you something newly married ladies you don't know brides bridal dress you know you've never seen at least you must have seen in a movie right so females are very much extra dressed you know helping the textile companies so now actually rbc's are like those bridal you know dresses having bridal dress extra membrane it does have an advantage you can move the way you want and this is that right so rbc the flexibility and food and gas exchange and many things but they are having extra membrane this is a disadvantage of extra membrane also or extra dress if you are having too much extra dress and you are passing through the narrow areas what will happen your dress gets stuck let's imagine a fresh rbc which is like a new bride having bridal dress with you know very big extra membrane or extra dress now if a new bridal girl has to pass through narrow tunnels passing through and let's imagine that her dress desk gets caught up at multiple places and wherever dress is caught up she leaves behind a piece of the dress and moves forward so progressively her dress will become larger or smaller when it will get progressively smaller so what will happen she will herself within the dress as dress is reducing she will become she will remain elongated lady or she will become circular packed into a small dress packed into small dress is that right am i clear no this is the risk in rbc that rbc have lot of extra membrane but it has to pass through very very narrow areas of circulatory system and if it does not have any special way to keep its membrane with itself then when rbc is passing through the very narrow capillaries it will keep on losing the chunks of the membrane and eventually what will happen that surface membrane for the rbc will become progressively less and shape of the rbc will become spherical shape of the rbc will become spherical because if volume is more and surface is less automatically things become spherical so rbc they were risk of becoming spherical if they lose their membrane and spherical rbcs do you think they can bend and they're flexible no so nature prevents this type of tragedy from rbc how the nature has provided this network of proteins which hold the membrane of the rbc tightly with the substance of the rbcs just like that a bride which is having extra dress but inside there are too much elastics which are keeping the dress with her as she keeps on moving if dress is stuck with elastic it is pulled so she does not lose his address at multiple places am i clear so these are the membranes these are the special protein networks these are called structural protein of rbcs right these structural proteins have a very important function they keep the membrane of the rbc highly flexible and stable and they keep the membrane of the rbc with the substance of the rbcs and these structural protein don't allow the rbc membrane to be lost here and there when rbc's are passing through narrow capillary structures am i clear no problem after this now what is the importance to learn it if you really want to know the names of these proteins these proteins are called spectrins spectrins right these black proteins are enchirin and kyrens right these proteins are called glycophorins or some of them are called 4.1 banned proteins band proteins 4.1 right there's no need to remember all of these name if you really want to remember the name remember just two spectrins n ankyrins but there are many proteins which are involved there are spectrines and there are actins and there are tropomyosins there is band uh 4.1 there's band three protein there's glycophorins no need to remember just remember the basic concept that look here this is a membrane of rbc and there's a network of proteins under it spectrine and anchoring and other protein anchor this network with the membrane so that when membrane is getting flexible these proteins keep the membrane and don't allow the membrane to be chunk pieces of membranes to be lost am i clear now let's look at the clinical evidence if in rethrobla if for example the genes the genes which synthesize these structural proteins if those genes are mutant and this network is not stable either they are deficient spectrum or there is deficient and current is that right again listen if you inherit defective gene for anchoring or spectrine or any other component can you make a good network no this rbc which is produced by person who has mutation in these pro g protein structure or mutation in the genes which make these proteins such rbcs with mutant network or weak network when they will come into circulation when such rbc will pass through narrow capillaries can it hold its membrane tightly no so this rbc will lose its membrane here and there and eventually these rbcs become spherical these rbcs will become spherical and the disease will be called hereditary spherocytosis because when you take the sample of the blood you find rbcs are spherical not by concave let me tell you how you decide on the slide that rbc is by concave or spherical look in by concave there is more hemoglobin on the edge and less hemoglobin in the center so in healthy bio concave there is more pinkish area on the side and central areas pale if you find an rbc under the microscope center is pale and periphery is pink it means this is normal by concave rbc are you understanding because central should be pale it has less hemoglobin and by concave edges are having more hemoglobin but when it is spherical when it is truly spherical rbc then there is more hemoglobin in the center isn't it so this rbc will stain without any central power so when you find an rbc under the microscope without any central power it means this is not by concave it is spherical rbc so if you in these patients because spectrine or anchoring or related proteins are mutant and these rbcs are not having the proper capability to keep the membrane with the rbc so such rbcs during circulation keep on losing the membrane and they become spherical and uh this condition because it is inherited so we call it hereditary sufferer cytosis hereditary the phero cytosins but if this problem is mild then we call it hereditary elliptocytosis if it is sphere then hereditary spherocytosis if problem is mild then rbc become elliptical not fully spherical then we call it hereditary alepto cytosis am i clear so now you will remember what is the purpose of these proteins this is a very important structural protein related with the rbcs and of course what happened to these rbcs when rbc's become elliptical or spherical can they bend do you think it's a very fat man passing through narrow tunnel can he fold on himself no so such herbicides get stuck into narrow areas especially in in circulation of spleen you know supply in the spleen there is special type of circulatory area through which rbcs have to squeeze their way and if elliptocate or uh spherocyte happen to be there it will get stuck there and then who will eat that rbc macrophages so such rbcs are very rapidly eliminated from circulation so we say there is hemolysis and due to hemolysis their rbc count and hemoglobin concentration become less and we say heritage spherocytosis is a form of hemolytic anemia because analysis occur and rbc count and hemoglobin concentration goes down so there is hemolytic anemia am i clear there's no problem about this so this was something about their structural protein then there are enzymes also within the rbcs but remember rbcs don't have mitochondria so they break down the glucose only partially they do only glycolysis so they have enzymes related with the glycolysis or rbcs can make energy through hexose monophosphate shunt so they do have enzymes for that system as well is that right so they have structural proteins and functional proteins structural proteins are spectrins and carine and related proteins which are responsible to keep the cell in biconcave shape and responsible to stabilize the rbc membrane and then the functional protein and functional proteins are enzymes related with rbc metabolism is that right and of course rbc does not have any nucleus is that right and usually its life is how much 120 120 days around that time their proteins become denatured they don't function well so rbcs become somewhat the membrane becomes somewhat rigid not as flexible as they are as newly born rbc's are highly flexible as rbcs become older and they're they become more senior citizens then they are not so flexible they cannot twist through certain situations and they get stuck into capillaries of sapling and their macrophages will eat them up am i clear right then a very important protein the most important protein which is present in the rbc is hemoglobin so let's talk about hemoglobin but i will talk very briefly about it that basic structure of hemoglobin and types of you globin actually during the synthesis of hemoglobin the first molecule which is made this molecule is called pyrrole ring so erythroblast first of all produce spiral rings then four parallel rings are put together assembled these are four parallel rings if they are put together this structure is called proto pore firing then if this is proto pore firing in the center of protocol firing if you put iron what you put iron then it is called heme is that right again erythroblasts make initially spiral rings assemble them into protophyrin rings and protoporphyrin ring in the center of that they put iron and then there is heme and then the synthesize the globin chain and with the heme with the heme they put one this is him proto profiling ring with iron and they put a globin chain right and now what is this called hemoglobin monomer what is this called hemoglobin monobar but basically hemoglobin is a tetrameric protein right so there are tetramers now listen actually the different type of globin chains which can be synthesized this was suppose alpha globin chain globin chain uh erythroplast can also produce beta globin chain which is called beta chains and it can also produce yes gamma globin chain and it can also produce yes another type of all of them of chains are with the heme and this chain is delta chain so globin chains can be alpha chains between gamma chain and delta chain is that right now these are different type of monomers of hemoglobin now if there are two monomers with alpha chain plus two monomers with beta chains then this hemoglobin is called hemoglobin a a for adult because in adult most of the hemoglobin has two alpha chains and two beta chains then an adult another variety is found 96 percent of the hemoglobin is of this configuration about two to three percent hemoglobin is two alpha chains with plus two delta chains that is called hemoglobin a2 that is called hemoglobin a2 then in fetus usually two alpha chains are combined with two gamma chains and that is called fetal hemoglobin hemoglobin is that right so what we really understand that alpha chains are present in all hemoglobin adult hemoglobin or a2 hemoglobin or hemoglobin but actually if two alpha will two beta this will become a relative globin a if two alpha are with two delta then these are and if there are two alpha with two gamma then it is hemoglobin f now let's have a test if two alpha with two delta what will they make hemoglobin a2 if two alpha with two beta hemoglobin a if two alpha with two gamma hemoglobin f another important thing actually fetal hemoglobin with gamma chains it has more strongly it can uh it has more strong affinity for oxygen so that it can really pull the oxygen from maternal circulation to fetal circulation so fetus is very clever it does not activate beta chain or delta chain genes it activate gamma chain genes so feet in the fetus hemoglobin is 2 alpha 2 gamma actually why this hemoglobin is an advantage for the fetus because this hemoglobin has stronger affinity for what oxygen so it can pull the oxygen from the circulation of the mother to the fetal circulation is that right okay another thing which i would like to mention here that if there is some mutation in the genes which produce these chains right then there can be problems for example if a person has mutation in mutant beta chains so it's not making the beta change at all let's suppose these are the genes this is alpha gene alpha gene this is for beta gene and beta gene this is gamma gene and gamma g i'm just giving you an example let's suppose if beta genes are defective then what will happen this person initially in fetal life will make alpha with gamma so that is which in which hemoglobin f but actually this baby after the birth he should make alpha with beta but if beta are defective he will keep on producing alpha with gamma is that right this type of diseases in which there is quantitative deficiency of any type some type of globin chain this type of diseases are called thalassaemias have you heard of thalassemias thalassemias are diseases in which there is quantitative problems with the production of globin chains right and certain globin chains are not produced with proper ratio right thalassemias right then we come to an other concept do you know something about blood grouping of and rh blood grouping you want to know something or you know it well you want to know it okay i'll talk very briefly about that that there are so many ways to group the blood group right typing of the blood grouping can be done but two important grouping i will talk about is blood grouping and rh blood grouping right first let me tell you what is meant by the blood grouping actually on rbc's surface right different people express different antigens right some people express okay i'll make a full chart here some people on the rbc's surface they only express a antigen and some people express only b antigens let's suppose these are four different persons person number one question number two person number three person number four now person number one on his rbc is he is expressing only a antigen is that right the antigens the persons who express a antigens on their rbcs they're called blood group a it's so easy and people who express b antigens on their rbc surface they are called blood group the some people are expressing the both antigens right so they are called blood group a b right a b and some of them don't express they simply express an h antigen actually h can be modified into a and b h antigen is expressed by all of them h can be modified into a or can be modified into b and some people h is there and it can it is not modified into a and b and h is not immunogenic it does not stimulate the immune system so practically we can say these people do not have a and they do not have b are you really clear what i'm talking about no yeah right so h antigen is present h molecule is present on all of them it can be modified into a or can be modified into the and in some people the enzymes which have a capability to modify into a and b they are not there so practically they don't have a they don't have b antigen so we call them blood group o so in a way this is blood group a right this is blood group b this is blood group a b and this patient has o o is no a no b is that right now there is another thing actually a and b antigens are present in environment also and these antigens are also present in microbes so when we eat many of these a and b antigens come to our git and they these antigens which are coming through foreign sources they try to stimulate our immune system they try to stimulate our immune system now listen for example person number one is person number one is blood group a now in blood group a person a and b antigen will be coming to his immune system stimulation from the microbe and from the diet but when a antigen will come a antigen will be perceived as self antigen because this antigen is coming from environment but it is also present in his own body so a antigen because it is his own antigen do you think this his person's immune system will make anti-antibody no so in this person the person who has a antigen he does not make nta antibodies but when b antigen come to his system right and b antigen is not present in his own system so his immune system is going to perceive b as foreign antigen so he'll make ntb so what really happens that antibodies present in blood group a patient are nt b and people who are blood group b right when their immune system is challenged by a and b foreign antigens they will not make anti b because b is their self but they will make nt a they will make anti antibodies these antibodies are called also heme glutames right anyway person with a and b both antigens are self antigens when foreign a and b antigens come through microbial diet do you think their immune system will make anti-air and tb antigens so they don't have antibodies but person who has no a antigen no b antigen whereas in this person's body through the diet through the microbe a and b antigens come he is going to make anti a antibodies as well as he is going to make anti b antibodies so is it clear that again person who has blood group a he is having a antigen on the rbcs and in his plasma he has anti b and antibodies person who has blood group b he has which antigen on rbcs which antigen on rbc's b and which antibody in the blood nte antibody right person who has a blood group a and b he is having which antigens expressed in rbc's a and b both antigens and in his plasma which antibodies are there no there are no nta no ntp other antibodies against other antigen may be there in the body you make him totally immuno incompetent okay person who has blood group oh yeah person who is blood group oh he does not have a antigen he does not have b antigen so he will develop anti a an ntb is that clear now we talk about abu incompatibility you heard of this isn't it now we talk about abn compatibility first listen a basic rule let's suppose you are going to do a blood transfusion this is a circulatory system of recipient person right if you bring the donors rbc these are the donor rbc which are going in his body and this is the donor plasma which is also going to his body is that right now listen carefully and donor rbc let's suppose this is donor rbc is a it means donor blood group is a and by mistake by mistake if you give a blood to a person who is b group it means this person has which antigen on his rbc b recipient has a blood group b and unfortunately you have given the recipient a blood which is blood group a so recipient rbcs have b antigen and nta antibodies anti-antibodies which are already present in the serum of a plasma of recipient and when you bring the donor rbcs which are having concentrated a antigens on the rbc membrane nta will attack the donor rbc then destroy the donor rbcs so what really happens in abio incompatibility these are the donor rbc's which have a risk of being destroyed in recipient circulation i'm the recipient okay let's suppose this is the donor please come here let's look have a look on the donor all right come on this side let's suppose this person has blood group a and i'm having a blood group b his rbcs are having which antigen a antigen my rbcs are having b antigen his plasma has which antibody nt b and my plasma has anti a clear now if by mistake you put his blood in my circulation when his rbcs will come to my circulation his rbc membrane has thousands and thousands and thousands of antigens concentrated and my plasma has nt a so my nta will attack that donated rbcs and destroy them and hemoglobin will be released in my circulation from the ruptured donors rbc's hemoglobin is released and this free hemoglobin will damage my kidney right produce kidney failure activate a lot of mast cells which will release lot of histamine and my blood vessels will dilate i may go into shock that is a dangerous situation right so donors rbcs in case of incompatibility will be destroyed in recipient circulation and produce problems but another important point but donors antibodies he was having anti-b antibodies his antibodies will also come to me but they will get rapidly diluted in my circulation right so donors antibodies usually do not attack recipient rpc but recipients antibodies do attack the donors rpcs if there's abn compatibility am i clear to everyone why don't his antibodies look his antibodies are in plasma he has a having ntb antibodies now his plasma fluid is diluted into all my plasma right and antibodies become so sub critical concentration that they don't effectively destroy my rbcs is that right but when his rbc comes his rbcs are having thousands and thousands of antigens concentrated on his rbc membrane can those antigens get diluted in my body no they remain concentrated on donors rbc surface so they are very effectively attacked by my antibodies so what really happens in abn compatibility is these are the donor rbcs which are attacked by the recipient antibodies and donors rbcs rupture in recipients circulation and produce problems but donors antibodies get diluted in the huge volume of plasma of the recipient person am i clear to everyone please have a seat you are about to kill me now yeah so is the hemoglobin from the donors that causes all the problems yeah hemoglobin which is actually when donors rbc is ruptured in recipient circulation then free hemoglobin uh produces the problem is that right for example homoglobin can leak through glumerular membranes and damage our kidneys especially proximal convoluted tubules anyway let's come back so now we talk about it that person who has blood group a can you give him uh a blood group yes can you give him b blood crop no because he has nta b blood group we cannot give because when b rbc's will enter into a circulation a person has ntb antibodies so donated rbc will be ruptured can he be given a b blood group no because again donors rbc will be destroyed by nt b can he be given o yes yes because o does not have a or b so ntb cannot destroy the o quoted rbc's clear now we come to person where the blood group b he has which antibody and t a can he get blood group a no can he get blood group b yes yes can he get a b no because n t a will destroy the a or which is a antigen and can he get o yes now we come to the person with blood group a b so this person does not have any antibody no anti-ano and tb can he receive blood group a yes can he receive blood group b yes can he receive a b and can he receive o yes why again person who has blood group a b he does not have anti-antibodies he does not have in circulation and tb antibodies so he receives a rbc's with a antigen or b antigen with a b antigen over antigen none of these rbcs are destroyed because he's not having anti or ntb antibodies but the person who has blood group oh he is having anti-a and t b antibodies so can he receive should he receive the blood group a no should he receive b no should he receive ap no okay should he receive o yes now if you really look at it what we see that every group every group can receive the o is that right because o rbcs of o blood group do not have a and b and t gen so whatever person's circulation they go they will not be destroyed by nt a or ntb so blood group o people are said to be universal donors they are said to be universal donor opposite to that when we talk about a b blood group right they can receive blood from everyone because people who have a b blood group they do not have anti antibodies they do not have anti b antibodies because they do not have anti antibodies and nt b antibodies so you put a b or a b or o rbcs they will not be destroyed so they are universal recipient so blood group is universal recipient and oh blood group is universal donor is that right i hope this concept is clear right now we talk about rh blood group only few words you want to have a break now rh antigen is present in some people's rbcs and it is not present in some other people's rbcs rh antigen was first of all discovered in some monkeys races monkeys rbcs so that is called recess antigen or rh antigen now the rbcs which are having rh antigen right rbcs which have rh antigen they are said to be rh positive and rbcs which do not have rh antigen they are said to be rh negative and if i say my blood group is a positive it means i have a antigen plus rh antigen if i say your blood group is a negative it means you have a antigen but no rh if i say you are a b positive it means you have antigen on rbc is b antigen and rbc as well as rh if i say you are o negative it means you do not have a antigen you do not have b antigens you do not have rh you understand this concept now the special precaution which we have to make about rh system is we'll talk about that precaution later first as i told you a and b antigens are present in nature so they come to us from microbes and from the diet rh antigen is not present in nature abundantly not present in microbes and rh antigen is not present in diet so it is not normally coming to us is that right now if i am rh positive person my rbc the rh positive person right because from the nature no rh antigens come i will not make anti rh but even if you put some other person's rbcs which are rh positive to my circulation still i will not make anti rh because rh antigen is considered my self antigen am i clear now but if there is a person who is rh negative if there is a person who is rh negative in that person normally anti-rh antibodies are not present are you understanding persons who are rh negative they know they don't make anti-arch antibodies spontaneously but a person who is rh negative if that person get rh positive rbcs in her body then that person can make anti-rh antibodies am i clear now i will give you a classical example which is also clinically related let's suppose there is a woman who is rh negative you know some women are rare it's positive and some women are rh negative let's suppose there's a woman who is rh negative and she gets pregnant and unfortunately she is carrying a baby which is rh positive of course that rx positive gene came from paternal side right let's suppose look at her situation this is maternal circulation mother circulation her rbcs are rh negative she does not have rh antigen and here is the happy baby right and this baby has an rbc which is rh positive this she's first time pregnant and this is rh negative mother which is carrying rh positive baby now what really happens that during the pregnancy but mostly just after the delivery a little blood from the baby goes to the mother about half ml blood right so what really happens when this first this is the first baby when first baby is delivered when this woman which is rh negative she was carrying out a positive baby fetus and when she delivers first baby at the time of delivery when placenta detaches from the uterus a small amount of fetal blood goes to the mother and then mother this baby is out of course right this first baby is out but during this delivery some of its blood went to mother which was rbcs which are alright positive no fetal rbcs were rh positive this baby has gone out no trouble to it but when mother immune system another immune system will receive rh positive rbcs do you think rh antigen is natural for mother no so mother will make anti rh antibodies now this lady who is herself rh negative but she is carrying which antibodies in her blood and tr antibodies she will not she will not have any problem herself because her rbcs are rh negative and anti-arch antibodies she has made due to stimulation coming from the first baby these antibodies will not disturb her let's suppose after two years she again become pregnant now this is she's having the second baby right and this baby is also rh positive this baby is also rh positive right but now mother circulation is different you know the naughty first baby he stimulated mother immune system on the way when he was out and mother made ntrh antibodies so mother was having anti-rh antibodies due to her prior exposure to rh antigen so when she will be pregnant and carrying the second fetus anti-rh antibody belong to igg group and it can cross placenta so it will come to this baby and this anti-rh antibodies from maternal plasma come to the fetus and bind with the fetal rbcs and destroy them so when this baby will be born this baby will have have anemia swear anemia because hemolysis is going on because maternal anti-rh antibodies are destroying babies or bases but this second baby also give some at time of delivery give some rh positive rbcs and mother immune system now make more anti rh and trouble is more for the third baby you know life is strange this time she is carrying the third baby i think this must be right why because maybe stimulated the mother by giving a little blood and mother made anti rh antibody second baby also gave and rh positive rbcs to the mother mother made a lot of antiox antibodies and a lot of anti rh antibodies come and now babies rbcs are destroyed in very seriously and when the severe destruction of rbcs then to compensate for these rbc's laws baby has excessive hematopoiesis and due to excessive hematopoiesis babies liver and spleen and large because you know in the fetus liver and supplement act as a metabolic organs but by the time of birth most of the metropolis is from the bone marrow but because in this baby lot of destruction of rbcs are going on so liver and supplement continue their hematopoiesis and they become enlarged due to increase in water voices and bone marrow also does so this baby is born with hepatomegaly and splenomegaly and still a lot of what severe anemia and lot of these rbcs which are destroyed they are releasing bilirubin unconjugated bilirubin which may go to the brain of this baby because babies are having a newborn having immature blood brain barrier so when these rbcs are rapidly destroyed they release the hemoglobin they release lot of hemoglobin which is eventually releasing bilirubin breakdown product of rbc's is bilirubin and this heavy amount of bilirubin may cross the blood barrier and this may go to the baby's central nervous system destroys cortex and basal ganglia so this baby will develop really weeping much this baby will develop mental retardation and motor disorders and problem like this right woman is determined to have more babies yeah they will there will be some good doctors like uh dr gigi will be there and she will do some treatment yes we'll talk about this for sure now unfortunately she was in the third world not taken care properly and she is very keen to have more children now this time what will happen the real sad thing again the baby's alright positive and what will be the problem with this baby the mother has so much rh and t ntrh antibodies that's a very severe destruction of babies or which is and baby has a very large liver very large supplement and still very heavy amount of voices cannot match the losses of rbcs so blood become very thick or thin thin because most of the rbc's are destroyed and heart of the baby fails to maintain the circulation is that right so baby also develop cardiac failure and in advance classes you will know when someone develop cardiac failure there is generalized edema so this baby has hepatomegaly splenomegaly and due to heart failure baby develop generalized edema and this baby will be very much edematous baby so we call it hydrops fatalis fetus full of water hydrops fatalis and mother cannot maybe deliver it through normal birth canal during this process either mother will die or some doctor in the third world he will cut the baby into pieces and bring it out to save the mother life or you will do c-section if the facilities are available and bring the baby out but full of water is that right and you relate many of these baby died within the uterus right mother is already having one child which is mentally and now she has this tragedy another problem during the situation occur that because in these babies hematopoiesis continues hematopoiesis continues in liver and spleen right now hematopoietic function in liver and sapling is different than hematopoiesis in bone marrow bone marrow is such a clever organ that it only allows mature product to go into circulation you are understanding from bone marrow when bone marrow is doing hematopoiesis do you think pro erythro blast come to circulation no only reticulocyte and rbc's come into circulation right so actually your bone marrow uh stroma is so much you can say uh so well functional that it only allows the mature rbcs wbcs and platelets to go into circulation but liver and sapling are not so good hematopoietic organs and if they continue their metabolism for a long time they allow the precursor cells also to jump into circulation so in these babies who are born with continued hematopoiesis and level and supplement they have lot of erythroblasts into their circulation of these babies when these babies were born right doctors took their cord blood and tried to see what is wrong and they found that these fetuses which are having sphere jaundice or having hepatocybin magali are in severe cases they having what is that generalized edema they found in the blood of these babies or newborn fetus there are a lot of erythroblasts because what is the underlying cause for that restore blastocyst present in the blood because the meta processes are going in leverage the plane and they allow the immature precursors also to come into blood so doctors at that time when they never understood the mechanism of this disease this just said this is a disease of a fetus in which lot of erythroblasts were found in the blood so they called this disease erythroblastosis fatalis what was this disease called condition of the baby erythroblastosis fatalis am i clear so that is why now yes we come to dr gigi the doctor gigi was asking is there in treatment she's very much concerned so we should be concerned about patients uh there is treatment now available what we do that now commercially available anti-rh antibodies are there there are injections available injectable forms of anti-rh antibodies the injection comes with the name of rhogam right now rh immunoglobulins rhogam rhogam's injections are available what doctors do it's international standard of pediatric you can say obstructed care that any woman who is rh negative right as soon as she gives birth to a baby immediately baby's blood should be checked if babies are ah positive immediately mother should be injected within 72 hours mother should be injected with injection of rogan what is the advantage of injecting the mother with rogan let's suppose this was her first baby bar we already knew mother was a negative and baby suppose a b positive so it means rh negative mother has given bus to rh positive baby so probably some babies rbcs are present in maternal circulation and these rbcs are rh positive we inject the mother with ntrh antibodies these antibodies will come and these antibodies will bind with the circulating fetal rpcs and destroy them when these fetal rbcs are rapidly destroyed in mother circulation so these rbcs are never detected by the immune system so immune system never make anti-rh antibodies in this way mother becomes safe for the next baby so this is international practice now that whenever rh negative mother give birth to rh positive baby mother within 72 hours of the delivery of the baby should be injected with rogam right these are anti-rh antibodies we also call it ntd antibodies rh antibodies rh gene or rh antigen has three types d c and e right anyway these antibodies are also called rhogam antibodies or anti-rh antibodies or ntd antibodies so that any mother who is rh negative herself give birth to rh positive baby that mother should be injected with anti rh antibodies so that in future rbcs and maternal circulation should be coated by those antibodies and antibody coated rbc's are rapidly eliminated by the macrophages of the mother and supplement so maternal circulation become free of fetal rbcs and because rbcs are rapidly destroyed so if they are present fetal rbcs are present for very short time in maternal circulation they don't have produce enough stimulation to the mother immune system so mother does not produce enough anti-rh antibodies yes what's your question is iggy placental barrier or is it igm pardon is it igg able to cause the central barrier i g g g igg yes this is igg antibody crosses the placental barrier this has some benefit also that igg antibodies every for example a woman who is from africa she has been exposed to african infections so all her life he kept on making anti igg antibodies against many microbes when she will have a baby so all the igg antibodies she has in her circulation they will go to the baby and baby will be protected against those infection is that right so every woman who becomes pregnant whatever pool of igg antibodies she has she gifted to the baby is that right so that when babies born to the new world right it should have some degree of protection amenity am i clear any more question yes now another thing why it igm does not cross listen when anyone anyone get infection initially you make igm but if infection come again and again you make ig g now listen uh for example you have a japanese woman here who is pregnant in her blood she will have igm against only those infection which has she has recent infection but igg antibodies are present in body for long time so when japanese woman is pregnant in her blood she has igg antibodies against the infection which she had 10 year back or 5 year back or 2 year back so actually everyone has lot of igg according to the exposure to the antigens in the past so whenever you get a new antigen you make igm for recent use and igg for long term use again this is very important whenever you get any infection right immune system make igm for recent use and igg for long term use so when any infection come again and again the igg keep on getting boosted is that right so what really happens that if mother give let's suppose theoretically if mother give igm to the baby then baby will get igm only against those antigens which mother received during her pregnancy but if mother is giving igg to the baby it means mother is giving all those protective manners which she developed against all the integers she which she was exposed in her life is that clear so what is more beneficial to the baby to receive igm or igg that is why placenta has receptors for ig g so maternal circulation igg bind with the placenta and then through pinocytosis process igg is taken from internal circulation to the fetal circulation and gifted to the baby yeah igm is not transported from the significantly from internal circulation to the gravy circulation and once babies born and mother nurses the baby feeds the baby then through the milk iga goes to the baby so newborn baby is receiving iga through the breast milk and already have received igg from maternal circulation this igg from eternal circulation stays in baby's blood for about 4-5 months that is why many people have a higher risk of infections or after that time right any more question yes um what if okay what if the mother is already positive and the babies aren't negative okay she has come up with a question if mother is rh positive and babies are negative what will happen nothing will happen but baby i hope should be born if mother is rh positive will she make antirh antibodies no no and secondly if baby has no rh antigen do you think baby has any type of risk from anywhere no nothing will happen this is a special condition in which our negative mothers are giving birth to rh positive baby so the risk is that that if it is first delivery the mother immune system is stimulated to make antiox and if it is she has previous deliveries also then maybe this baby is born if mother had already developed anti-rh antibodies then this baby may be suffering but if mother is negative and babies are negative do you think there will be any problem not at all so they give one time and then they never give it again no they just give when rh negative mother gives birth to rh positive baby they give injection once after the what is this delivery of the baby then they don't give it yeah right any question no class dismiss thank you

Channel: Dr. Najeeb Lectures

Views: 525,355

Keywords: erythropoesis, red blood cell life cycle, physiology, red blood cell break down, erythropoiesis, old and damaged red blood cells, plasma, erythrocytes, oxygen transport in blood, red blood cells, hematology, rbc, red blood cell production, dr najeeb lectures, blood cells, red blood cell, erythrocytes red blood cells, usmle, red blood cells function, red blood cell lecture, red blood cell by dr najeeb, red blood cell new lecture, blood cells lectures, hemoglobin dr najeeb, rbc lecture

Id: ZLuACVlG77U

Length: 83min 33sec (5013 seconds)

Published: Mon Mar 22 2021