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I think we should be live now. Wait. Can you, can you like give me a minute? Yeah, yeah, she'll take him in the door. Can we, can we start at 676, 606. Is that too late? We can do 6050 fine guys. If you're, if you're watching right now, can you please uh just tell me if you can hear us? Oh my God. No way how people could take that, bro. Uh in the charge you card, please. Anyone let me know you can hear us or not anyone. Yes. Lovely good stuff. Uh We'll be starting in like three minutes guys. Um Last time it was genetics. Hopefully some of you guys saw me um this time it's gonna be Erika who's gonna be doing hematology. Uh It's great stuff. It's a great preparation for your um mocks. Um So yeah, hopefully you guys are ready for your mocks. Um Honestly, the mocks aren't that bad. Uh Just take it, take it as a learning curve, but the main step forward is from your mocks, especially for, for p if you are imperial. Um Look at, look at, look at the content. And then from now on, from the mocks onwards to your actual exams, you want to basically solidify and consolidate your knowledge. Um So just basically just repeating like flashcards, repeating what the active learning you do. And also looking at um main thing being questions. So questions from a lot of tutorials like this, we'll be doing a lot of stuff in BRS as well. So we, we'll be doing endocrinology, cardiology, um and neurology as well soon uh in, in this month. Um and particularly for p you're looking at things like hematology, genetics, cells and immunology. Again, we'll be doing a lot of that. So make sure to answer questions, be interactive, learn from it. Um No one cares you go right or wrong uh and ask questions. All right. Um So yeah, go now. All good to go. Uh Now how do I change the slides? Um Yeah, there you go. Uh Yeah, great. OK, cool. I'll just hand over to her now. Um Any questions put in the chat, I'll be there and I'll be in the background as well. Um Please make sure to interact, ask questions, um give answers and uh yeah, hope you guys enjoy um leave your feedback at the end. Um I'll share the link, link with you guys right at the end as well. Um But yeah, good luck and I'll hand it over now. Hi guys. So, um as I, she said, I'm a psychogenetic at Imperial and I'll be taking you through this hematology uh tutorial. And if you do guys have, if you do, if you do have any questions, just put it in the chat or um I put my email here so you can email me at the end of it. If something does come up. Ok, outlined for today, we're gonna look at the first thing we'll look at is hemostasis uh followed by anemias, uh different types of anemias. And then we'll look at interpreting FBC S followed by blood groups. So that's like the A BO system, Rh system and some stuff about transfusions. And then we should be able to wrap up. There'll be some questions in between as well. So hopefully you guys should be able to answer that and you can just put your answer in the chat. OK. So, hemostasis, what actually is it? Um So it's basically a process that's involved in clot formation and the whole point of it is to prevent and stop uh excessive bleeding. Um It's usually like the first step to uh wound healing after like trauma to a blood vessel or some sort of injury. And it's split into four different parts. So we've got um vasoconstriction, the first one followed by primary hemostasis, uh secondary hemostasis and then fibrinolysis. So the bulk of it will be focusing on primary and secondary hemostasis. Um The vaso constriction part is basically uh kind of self explanatory blood flow to the area of um where this trauma is gonna be reduced when they um constrict. And um yeah. So, primary hemostasis. The first step we have here is platelet adhesion. The whole point of this is to make um an unstable platelet plug. And we do this by um platelet sticking to the damaged endothelium. It can happen in two different ways. Um So it can e so the platelets can either directly uh stick to the damaged endothelium by um uh by binding collagen to the GP one A receptors on it. Um like shown on the right side of this diagram or indirectly via binding of V WF to the GP one B receptor as shown on the left side of this diagram. Um And then, so the platelets um become activated after this and you'll see a shape change from like disc around it. So like platelets are normally like this shape. Uh but once they become activated, they kind of like they become round. And you also have spicules formed. The idea of this is um just for them to like help aggregate and like stick together. Um Once these platelets are activated, they release uh Granules which contain um ADP fibrinogen and B WF Thromoxane A two is also generated and released. And what this does is it basically um Thromoxane A two is involved in vasoconstriction. So, again, reducing blood flow to this area so that we uh reduce bleeding as much as possible. And um also involved in like platelet aggregation. Um The ADP which is released, it binds to receptors on other platelets. Um more specifically the P two Y 12 receptor, what this does is it uh amplifies platelet activation and aggregation. So it kind of like activates more and more platelets. And then um this whole like thing is like all of this is basically positive feedback because we have um just amplification of this whole process. Um So how does platelet aggregation actually work? Um So once the platelets are activated, um there's expression of the GP two B and the GP three A receptors on them and fibrillin is able to bind to these receptors. Uh So, like I said before, when they were activated, fibrillin was released, right? So, um fibroin binds to these receptors and links platelets together to form a platelet plug. And currently the platelet plug is unstable. But in secondary hemostasis, we'll see how um the uh platelet plug is basically more stable. But before we get onto that, we're gonna look at some um antiplatelet drugs. So, um platelets last in the uh bloodstream for about like seven days, 7 to 10 days. So each of these um drugs, a dose of them also lasts for seven days until all platelets are replaced. Um An example of these um antiplatelet drugs would be um Aspirin. Aspirin works by inhibiting the production of thromboxane A two by irreversibly blocking the action of cyclooxygenase, which is basically like it's like an enzyme which helps make thromboxane A two. And by inhibiting the action of cyclooxygenase, we make less, less thromboxane A two. And as a result, we reduce platelet aggregation. Um clopidogrel um kind of has the same effect but it's a different mechanism. So what it does is it blocks ADP, which was released from our platelet Granules earlier on and it blocks the so not, it doesn't block ADP, it blocks the ADP receptor which is P two Y 12 on other platelets. And um what that does is it's gonna minimize platelet activation and aggregation. Therefore, um antiplatelet drug. OK. We have a question now. Um which plasma protein is essential for mediating platelet capcha on collagen? I'll give you about 30 seconds. Maybe you could put it in the chart. Any ideas anyone? OK. Um The answer for this is uh VWF. Um Hopefully that makes sense because I just covered what um what it does. But um it's basically involved in platelet adhesion in the first step uh when we looked at this. So, um yeah, so they probably can um stick to the damaged endothelium uh indirectly by binding the B WF to the GP one B receptors on it. OK. Um We talked a bit more about secondary hemostasis now, but before that, um just a quick introduction of what clotting factors are because this is essentially what he secondary stasis all about. Like this is what's involved in the coagulation cascade. So, clotting factors are proteins in the blood that work together in a sequence of steps known as the coagulation cascade. And the idea of this is to form a stable fibrin clot and stop bleeding. Uh Most of these factors are made in the liver factor A and V WF are made by endothelial cells. Uh V WF um can also be made in megakaryocytes and then put into platelet Granules. So, platelets, um platelets are basically derived from this. These other cells called megakaryocytes for context. Um Vitamin K is also needed for the carboxylation of glutamic acid residues in factors 279 and 10 for their function. Um We'll touch on why this is important later. Um and why, why it's relevant for certain drugs to actually work. But just remember that Vitamin K is needed to make factors 279 and 10. Uh where do these factors work? So they work on the exposed phospholipid surface of platelets and um calcium. So CO2 plus ions are also very important in binding of co factors to these surfaces. But that's pretty much all you need to know about it. OK. Um Secondary hemostasis. The first step of this is initiation. So factor seven A is just floating around in the blood and it binds to tissue factor, which is um it's located at sites which are not normally exposed to blood. So um seven factor seven A will bind to tissue factor forming this complex. Um the seven AF complex, um this complex will then uh activate back to 10 into 10 as well as nine into 98 and factor 10 A also cleaves five factor five into five A. What then happens is factor five A and 10 A combine together to form this prothrombinase complex. And this prothrombinase complex activates prothrombin, which is basically another word for factor two into a small amount of thrombin factor two A. So protomin complex converts factor two into factor two A and factor two A is what binds to platelets and activates them. So once um once the platelets are activated, the um thrombin, the factor two A will also activate factor eight into eight A five into eight A and also 1111 A. This is your amplification stage. I appreciate. There's a lot of steps with secondary hemostasis. But um in order to memorize all I did was just write it down multiple times until it was in grade in my head. Um But yeah, so after this, you have the propagation stage and this is when the most amount of thrombin factor two A is generated. Uh factor 11 A is gonna convert more nine into nine A factor nine. We're gonna combine with eight A to form a complex which will amplify the activation of 10 to 10 A. And this again will be used to form your pro domina complex, which remember was factor five A and 10 A and this will cause a rapid burst in thrombin generation. And thrombin is what cleaves the circulating fibrinogen to form the insoluble fibrin clot. Um So the whole idea of this is to make as much thumb as possible. And um fibrinogen is soluble whereas fibrin is insoluble and it's able to hold the platelets are much better and like make a much stronger clot than, than we would have done with just fibrinogen, which is why in primary hemostasis, we say that you're making an unstable platelet plug. Whereas in secondary hemostasis, you're forming an insoluble fibrin clot which is stable. Um OK. So, regulation of secondary hemostasis. Um This whole process is tightly regulated to ensure that clotting only occurs when needed and that you're not, you know, having random clots being formed when unnecessary. Um antithrombin is an example of a natural anticoagulant and it inhibits thrombin and factor 10 A and its action is amplified by Heparin, which is a drug that will come on to again later. But for now, just remember that antithrombin is a natural anticoagulant and it will inhibit the whole like clotting process. Um Protein C and S um thrombin will bind to thrombomodulin which is found on endothelial cell surfaces. And once thrombin binds to thrombomodulin, it leads to the activation of protein C and activated protein C will inactivate factors five A and eight A which remember are really important in like the propagation phase and to make thrombin. So, ultimately, a uh the activated protein C is really important um to make your insoluble fibrin clot it and without this. So with the A PC is gonna inactivate the factors five A and eight A in the presence of Cofactor protein S. Um Yeah. And so the whole point of this is again to inhibit clotting. On the other hand, your fibrinolytic enzyme plasmid kind of does the opposite. Um The what what this does is um you have your tissue plasminogen activator which activates plasminogen into plasmin. And it's like an enzyme which is gonna break down your um insoluble fibrin clot. Um Plasmin can also, this also sort of needs to be regulated because um plasmin can break down other plasma components such as fibrinogen factor five A and A A. So plasmin is inhibited by antiplasmin. Um OK, moving on to clot and bleeding therapy. So, uh thrombolytic therapy is basically when recombinant TPA is given to a patient and it's usually uh administered for patients that are experiencing something like pulmonary embolism or ischemic stroke because these tend to be life threatening and pulmonary emboli pulmonary embolism is basically when you've got a blood clot in like your lungs. Um and the patient is given recombinant TPA uh which will work by activating plasmin that's then gonna break down clots and it needs to be given as quickly as possible because the effect is time dependent. Um Tranexamic acid is um a another form of clot slash feeding therapy. Um It's a synthetic derivative of the amino acid lysine and it acts as a competitive inhibitor. Um because what it does is it prevents plasminogen from binding to lysine residues on the fibrin and it prevents it being activated into plasma. So essentially, when there's no plasmin or less plasmin being made, you can't really break down the um insoluble fibin clot that you have. OK. We're gonna look at some anticoagulant drugs now. Um So Heparin uh I previously mentioned that antithrombin is not, is a natural anticoagulant and it's um and its usage is basically amplified and its effect is amplified by this drug called Heparin. Um This works because um Heparin has like, it's basically got these like long chains which are able to wrap around both thrombin and antithrombin. Remember, antithrombin um inactivates thrombin and factor 10 A, right. So he, so the long chains kind of like wrap around thrombin, antithrombin force them to interact with each other and the antithrombin just kind of like turns off the thrombin. Um So yeah, uh ultimately, you've got inactivated Fact 10 A and two A and this is administered intravenously or by subcutaneous injections. Uh Warfarin, this is a Vitamin K antagonist. Um It reduces the synthesis of factors 279 and 10 by the liver because as I said, Vitamin K is used to make these factors, but um Warfarin will act as an antagonist to it. And it's given as an oral tablet and it has anticoag and its anticoagulant effect needs to be monitored by regular blood testing. It also takes several days to take effect because Warfarin will only reduce the synthesis of new factors rather than inhibiting existing ones. So your body will still have all the existing fact, like it will still keep all the existing factors. It has, it just means that less new factors are made. Um We also have um dia which are basically direct oral anticoagulants. Um They inhibit either thrombin, uh your factor two A or Factor 10 A without the involvement of antithrombin. Ok. Um So, clinical relevance of hemostasis. Um So uh we'll look at some disorders that um are linked to hemostasis. So this slide covers like some bleeding disorders. Um An example of this is hemophilia, which is an excellent recessive disorder. Um You have two different types. You have hemophilia A and you have hemophilia B. Um hemophilia A is when you have a deficiency of Factor eight and hemophilia B is when there's a deficiency of factor nine. So when you, when you have hemophilia, there's gonna be impaired clotting because of these um lack of clotting factors. Um and therefore, patients are also prone to spontaneous bleeding in joints and muscles. Um Another another um bleeding disorder would be thrombocytopenia. This is when patients have low platelet count. So another word for platelets is thrombocytes and pia just refers to lower a lower amount of these thrombocytes. Um and it can be caused by bone marrow disorders or certain autoimmune conditions. Um Clinical manifestations of this would be uh patients are likely to experience easy bruising, um nose bleeds and gum bleeding, but we can treat this with platelet transfusion. Um this sort of links on before Vitamin K deficiency. Um obviously, if there's deficiency of this vitamin, you're gonna have less factors 279 and 10 and experience like uh impaired clotting again. Ok. Um This slide talks more about like thrombotic disorders. This is kind of the opposite of bleeding disorders. So you're basically more likely to form clots um when sort of unnecessary um DVT deep vein thrombosis is an example of this. So it's a condition where there's abnormal clotting in the veins and these clots can also travel to the lungs and cause pulmonary embolism and symptoms of this would include or symptoms of DVT DVT in general would include swelling, pain and redness in the leg. But if these clots do travel to the lungs and cause pulmonary embolism, uh patients can also experience sudden onset dyspnea, chest pains, Ayia possibly hemoptysis as well. So, dysnea refers to um it refers to shortness of breath to keep is basically abnormal rapid breathing, which makes sense. Obviously, if a patient is out of breath, they're gonna breathe much faster and possibly hemoptysis, which refers to like coughing up blood and this can be managed by using anticoagulation therapy. Um So I just went through a few examples of anticoagulation therapy um such as Warfarin Heparin, um direct oral anticoagulants. Uh You can also use compression stockings that um patients can wear and this is to reduce DVT risk because like I said, patients can experience swelling, pain and redness in the leg. Um uh Factor Five, Leiden is a genetic mutation which basically causes resistance to activated protein C. And um this increases risk of venous thrombosis. Remember, activated protein C um inactivates your factor five A and eight A. Therefore, there's an increased, um you know, there's an increased chance for clotting to occur and increased risk of venous thrombosis occurring. Um OK, this slide just kind of refers to all the different like um uh cells in your bloodstream uh derived from your hematopoietic stem cells. And IC called the erythrocyte because we're gonna take a closer look at red blood cells now and like anemias. Um So what actually is anemia? Uh it's a reduction in the amount of hemoglobin and a given volume of blood. So, ultimately, lower concentration of hemoglobin than normal. Um And obviously, if you have less hemoglobin, it's very likely that you're gonna have a reduced blood cells because the hemoglobin is contained within your red blood cells. Um And the mechanism for this is either due to failure of production of red blood cells, loss or destruction of these red blood cells and anemia can often be classified into three different types. Microcytic monocytic and microcytic um taking a closer look at microcytic anemia. This is when your red cells are smaller than normal and it can be caused by a defect in he synthesis. Uh It can also be caused by a defect in globin synthesis. This is known as thalassemia, which is a genetic disorder and people can present present with alpha or beta uh thalassemia that's uh dependent on which chain that was affected um ultimately caused by um iron deficiency. And as you can see in this like um um image that we've got here, some of these red blood cells are smaller than the average uh which shows us that it's microcytic anemia. Um normal cytic anemia, your red blood cells are the same size as normal, but you still have lower hemoglobin concentration. Therefore, um anemia and this can be caused by different things such as um heavy bleeding. So, acute blood loss, um which can happen through trauma. It can happen through surgery or gastroin intestinal bleeding. It can also um be a. So tic anemia can also be a result of failure of production of red blood cells. And this can be again because of various different reasons such as bone marrow failure or suppression. It can also lead you to re renal failure because um the um kidneys are basically, they produce this hormone called um erythropoietin. And that's very essential for the production of red blood cells. So, if you have renal failure, this can be reduced permetin and therefore le less red blood cells made um hemolysis. Uh this is basically destruction of red blood cells. This can happen because of um different reasons. But here we're looking at uh sickle cell, for example. So as you might already know, sickle cells have this crescent shape. Um unlike normal healthy red blood cells, which are like round and have a biconcave disc. Um So, due to the shape of these sickle cells, what happens is they, um they kind of tend to pull in the spleen and they get trapped there. And due to this like um pooling of red blood cells in the spleen, you get this thing called splenomegaly, which is basically an enlarged spleen. Um So all of blood gets kind of like trapped there. You also have and then um these red blood cells are also, they start to get destroyed, which means fluid leaks out of these um red blood cells. And again, the spleen just that swells up. Um And due to all of this, um and the enlarged spleen, you, the patients tend to experience a lot of pain as well. And this is referred to as sickle cell crises. And again, due to the hemolysis, you tend to lose a lot of hemoglobin and red blood cells that you experience anemia as well. Ok. Macrocystic anemia, this is when your red blood cells are larger than normal and um patients will present with an area of central pallor. This is basic, this basically means a larger um area of paleness in the middle and causes of this could be because of a lack of vitamin b12 or folate. And this is more specifically referred to as megaloblastic megaloblastic anemia. Uh It could also be because of hemolysis. It can also be due to pregnancy in pregnancy. There tends to be a greater demand for uh vitamin b12 and folate. Uh because because of the fetus and since there's a greater demand, it's also likely that the mother might be deficient. Um and also uh liver disease and ethno toxicity. Um you might be able to make out in these two images that um the top one, the patient has microcytic anemia because there's, there's like a larger area of paleness in the middle. That's, that's what we refer to as um area of central pallor. And in the healthy individual, just um the red blood cells look a lot more kind of it. It doesn't really look like there's much paleness in the middle. Therefore, we can conclude that this person is healthy like, well, their red blood cells are healthy. Ok, megaloblastic anemia. This is um uh so a specific type of macrocytic anemia caused by vitamin b12 or folic acid deficiency. Um and it happens because vitamin b12 and folic acid are very important for the production for like the maturation of uh the red blood cells nucleus. But because of because we're like deficient, um the nucleus maturation is delayed and but the cytoplasm continues to grow. This results in a larger than normal precursor to the red blood cells. And um you also tend to see um hypersegmented neutrophils, tear drop cells and oval macrocytes in under the microscope. And some symptoms of uh this anemia would also be paresthesia, which is basically pins and needles and like ting. So that's like tingling and numbness and um mood changes such as irritability and depression as well. Um ok. So iron deficiency anemia. Um this is one of the most common types and this is um again, when um when you can like, one of the reasons could be because of increased blood loss. This could be because of different reasons due to gastrointestinal bleeding, um hookworm infection or menorrhagia, this is, this is referred to um uh this menorrhagia basically means uh people that have heavy menstrual periods. So they lose a lot of blood. Um It could be due to insufficient dietary intake. Um This is often seen with uh vegetarians or like vegans because meat tends to have a very high amount of iron and obviously, vegetarians aren't, wouldn't be able to get that uh malabsorption. Um This is seen in patients that have celiac disease. Um and it can also be seen in pregnancy and infancy because there's increased demand for iron. Um Some symptoms of this would include uh fatigue, uh pallor, breathlessness, um brittle nails and colony. So in the image on the right, um you can see this patient has like dipped fingernails. This is what uh colonia is. It's basically when patients present with like spoon shaped nails, um and angular chilosis refers to the image uh under it. Um When patients have like redness and dryness in like like around the crevices of their mouth. And these are just some uh clinical manifestations of iron deficiency anemia, but it can be treated with um iron replacement therapy such as uh ferrous sufic um tablets. Um OK. Now, we're just gonna look at some different colors of red blood cells. Um So, OK, hypochromia refers to red blood cells that have a larger area of central color than normal. So, they're basically a lot paler in the middle and you can see this in the image on the bottom, right. Um It almost just looks like there's not much hemoglobin in it at all. And um the cells also tend to be flatter polychromasia is when um you have an abnormally high number of immature red blood cells. And um this is a result of prematurely being released from the bone marrow. Um And this is when, when red blood cells are immature, they still have their nucleus, which is what causes the blue tinge. Um The blue tinge comes from the um high RNA content and um you can see that in the middle image on the right here, um the red blood cells um look, they basically look quite blue, like I said, due to the high or RNA content. And um you can tell that these are immature red blood cells, which the fancy term for this would be reticulocytes. Um And you'll see this in cases where a patient has experienced heavy blood loss, like a lot of blood loss. Or for example, if there's hemolysis occurring because the bone marrow um uh what it does, it, it tries to make up for all of the red blood cells that have just been lost and um releases them into the blood uh as soon as quick as it can basically. So prematurely, even when um when they still have their nucleus present. Ok. We have another question now. So uh in what type of anemia may you find hypersegmented neutrophils on a blood film? Uh It's, it's one of the anemia that I just mentioned. Um So yeah, um I'll give you about a minute. Maybe you could type it in the chart. Uh Yeah. So myeloblastic anemia. That's correct. Um Yeah. So megal uh megaloblastic anemia is caused by a deficiency of vitamin B12. So, uh yeah, you are right with that one. Um which cells would you expect to be increased in the blood film of patients with increased bone marrow output again, I'll give you about a minute for this. Ok. Um The answer for this would be polychromatic cells. Um It's funny if you didn't get it because um I understand that all of this is like very new content for you guys. But the reason why it would be polychromatic cells is because um polychromatic cells are basically like immature red blood cells. And you, there's gonna be a lot of immature red blood cells in the blood stream when there's like um uh when, when they're being prematurely released from the bone marrow. And this happens in cases where there's like a lot of blood loss or destruction of rbcs because the body basically recognizes that, oh my God, like we've lost a lot of red red blood cells and I need to make up for this. So the bone marrow just kind of like it tries to work over time and then just keeps pushing out these red blood cells as soon as possible. And whilst doing this, it does it so like it tends to do it even before those red blood cells fully mature. Um hence, hence, it pushes out immature red blood cells, which are your polychromatic cells. And the reason why they're blue, like I mentioned is because they immature red blood cells still have their nucleus and the RNA content in them is what makes them blue when they're stained um to be looked, looked at under a microscope. So I hope that makes a little bit more sense now. But um if you guys still have any questions, feel free to just ask me now or like email me and I'll get back to you. Um ok, I think we're gonna ignore that question for now. Um But yeah, I would be focusing on um full um interpreting full blood counts now but before that, um let's just take a five minute break because yeah, uh we've got about halfway through. All right guys. Um So yeah, hope everyone's back and break. Um So, like I said, we'll be looking at um interpreting for blood counts now. Um So we had a lot of folks on red blood cells before, but since we're looking at um FP CS, we're gonna take a lot like a greater look at all of the white blood cells we have here, but we're not gonna go into too much detail because um I think the first year you don't need to know too much other than like what does high neutrophil like, what is high neutrophil um suggest or like low neutrophils? And like, you don't need to know the uh reference numbers either just like a rough idea of what um high or low amounts of different leucocytes mean. So, um before we start with that, um just a quick introduction about some of the do um white blood cells. So, neutrophils, um these are derived from your common uh myeloid progenitor as you can see in this image here. Um They're derived from your myeloblast and they always have this segmented lobulated nucleus. Um They tend to have a 7 to 10 day survival in circulating blood before they migrate to tissues. And um the main role of neutrophils is basically to carry out pathogen vocs and like fight bacterial infection, eosinophils. Um These are also similarly derived from your myeloblasts and they spend less time in circulation than your neutrophils, more time in tissues. Um but they're different in the sense that um they have a blob nucleus. So as soon as you see like a structure with a bilobe nucleus on a um on a microscopic image, it's very likely that it's an eosinophil. They also tend to have a uh like bright pink appearance because the Granules in it um tend to like stain bright pink um on standard H and E stain. And the main function of eosinophils is defense against parasitic infection using enzymes which are released from those Granules. Um basophils, uh these tend to have a very dense appearance under microscopes. Um again, have like a pink purply appearance. Um they have a lot of enzymes in them such as histamine heparin and proteolytic enzymes. Um what they do is they modulate various immune responses and bales can also be um involved in certain hypersensitivity reactions. Um monocytes, these um are, if you can see on this are again derived from your myoblasts, they last several days in circulation. Um and they, they carry out phagocytosis of bacteria and fungi, they also act as an antigen presenting cell. Um mo monocytes can then sort of like they, they can develop into macrophages. They do this when monocytes migrate to tissues and then they'll develop into macrophages which have a uh which more specifically have a scavenging voc function um and sort of a golf uh pathogens. So in the images at the bottom of this slide, I hope you can see um I try to include an image of all of these different uh white blood cells. Um uh on the on the left to the very left, you can see um neutrophil where you can see like a segmented nucleus. And next door, we've got the eosinophil which has a blob nucleus and you can see those distinct pink uh Granules and in the middle of basophil which has a very dense pink pebbly appearance. And lastly, we've got the monocyte and the Macr. OK. So actually interpreting FB CS. So, neutrophilia, this is when you see a higher than normal amount of neutrophils and this indicates bacterial infections because like I said, neutrophils are heavily involved in fighting off bacterial infection. So as soon as you see high neutrophils, just think bacterial infection or some sort of inflammation stress. It could also be due to leukemias and um pregnancy or infarction which is basically tissue death. Um neutropenia is like the opposite of neutrophilia is when you, it's when the patient is presenting with a lower than normal amount of neutrophils. And this can be due to bone marrow suppression because remember that neutrophils are made inside the bone marrow and then released into the bloodstream. Um or it can be caused by chemotherapy because in chemotherapy, um what happens is the neutrophils, they tend to be, they basically get destroyed faster than the bone marrow is able to make them. So ultimately, you're left with lower than normal amount of neutrophils, lymphocytes. Um uh lymphocytosis refers to a higher than normal amount of lymphocytes, lymphocytes. I haven't really touched on in the slide before. But if you look at this image here, they are derived from your common lymphoid progenitor and then differentiate into t lymphocytes. B lymphocytes and um yeah. Ok. So, lymphocytosis, um these are heavily involved in fighting off viral infections. So, if you see a high amount of lymphocytes is you could assume that the patient has a viral infection or maybe there's um some sort of a lymphoproliferative disorder or autoimmune disorder, which is causing this lymphopenia is the opposite. So a lower amount of lymphocytes than normal. Again, this is likely to be due to bone marrow failure because they are made in the bone marrow. Um monocytosis is when you have a higher than normal amount of monocytes and monocytes are um involved in P cytosis of like bacteria fungi. So you can assume that if you're seeing like monocytosis that the patient has chronic infections, um or like inflammatory condition, eosinophilia. So, eosinophils, um, the main thing you need to think about with the eosinophils is they fight off parasites. So, um, a high round of eosinophils suggests that the patient might have um an allergic reaction such as asthma, eczema or maybe an allergic reaction to certain drugs. Um, or they're fighting off parasitic infections or maybe even autoimmune diseases and lastly, basically, uh which is quite rare but it may indicate an allergic reaction. OK. A question, a full blood count report shows a raised neutrophil count. What is the most likely cause of this? Um I'll give you about a minute to answer this. Uh Yeah, bacterial infection. B is the right answer. OK. Uh We're moving on to blood groups now, uh blood groups and transfusions. So uh as you guys probably know already, uh our blood groups are, are organized using the A B system. So I think the diagrams basic, it kind of sums everything up. Um uh So basically, if some, if someone has uh if someone's blood group A, so um their red blood cell type, their red blood cells are gonna have a antigens on them. OK, to start off with all of our red blood cells have antigens on it. And based on what antigens we have on our red blood cell, that's how we decide what group, what blood group someone is and they can either be any of these four different groups. So, Aba B or O. And um so people that are group A, they have a antigens on their red blood cells and they tend to, they will, they will have anti B antibodies in their plasma. And people with group B blood type will have B antigens on their red blood cells and anti A antibodies in their plasma. And this is always gonna be the case. You're never gonna find someone with um like a antigens on their red blood cells and also anti A antibodies in their plasma because this would just mean that um the, the antibodies and the antigens will kind of like bind together and cause like um the blood to agglutinate and you're basically not gonna survive survive if that happens. So just remember if I'm blood group A, I've gotta have a antigens on my red blood cells and the opposite anti B antibodies in my plasma group BB antigens on my red blood cells and then anti A antibodies in my plasma. Um with group A, they're gonna people with that are group A um have both A and B antigens on their red blood cells. So um I wanna ask you guys, what do you think, what antibodies they're gonna have in their plasma? Um Give you like like a minute to answer this as well. You can put it in the chat. If not, I'll go through it because um yeah, I haven't actually explained this to you before. It's a bit of a trick question because um just remember that if I, if I have a antigens on my um red blood cell, I pretty much can't have anti a antibodies in my plasma. Otherwise, um my blood will basically start clotting. Yeah. So nothing. Um people with um group A um group A B will have no antibodies in their plasma at all, but they will have both A and B antigens on their red blood cells. Um People with group O, they group O blood group like they have no antigens on their red blood cells whatsoever. Um in terms of antibodies in their plasma is gonna be the um opposite of A B. So they're gonna have both anti B and anti A antibodies in their plasma. Um Why is knowing all of this relevant? So this is, this is important for us to know because uh when we're doing blood transfusions, we can't just give any type of blood to anyone. The whole idea is that we give the right type of blood otherwise um uh the blood will start to clot and the patient can undergo a hemolytic transfusion reaction. So um the key thing to note here is group O is like a universal donor. So someone with the group oh can donate to any group because they have no antigens on their red blood cells and they can, but they can only receive from group O because, because they have uh both anti A and anti B antibodies in their plasma. Whereas group A B is kind of the opposite. So people that are group A B, they can only donate to group A B but um they can receive from all groups because um because they have no antibodies in their plasma. So there's gonna be like no agglutination um and group A B, sorry, group A um they can donate to group A and A B. They can receive from group A and O. Group B can also, they, they can also donate to group B and A B and can receive from group B and O I hope that makes sense. I know this is quite confusing but um I think like like the key takeaway here is um that group B, you can donate to all groups, but you can only receive from group O and in group A B, you can receive from all groups, but you can only donate to group A B. And obviously, if someone's the same blood group, if so, if I'm group A and I wanna donate to someone else in group A, that's, that's the safe, like you can definitely do that. Um So yeah, this is important because when we're doing organ transplants or blood transfusions, uh A mismatch blood group can trigger an immune rejection and um with blood transfusions. So, identifying ab or blood types will um is essential to ensure compatibility and prevent these ho hemolytic transfusion reactions. Um HD FN. OK. HDF N is hemolytic disease um of the newborn. Um So with the A B system. Uh so OK. So the antigens on our red blood cells are IgM antibodies and they can agglutinate um your red blood cells. But these can't really, they, they can't cross the placenta. So if um the mother is blood group, A for example, and she's having a baby that's blood group B, it doesn't matter that you're not gonna, the baby's not gonna die because of hemolytic transfusion reaction because these IgM antibodies can't cross the placenta and HDF N won't HDF N is, yeah, like I said, hemolytic disease of um the fetus and newborn. But you can just refer to as HD N which is hemolytic disease of the newborn. Um OK. So we're gonna look at codominance because you guys might be wondering why group A B can exist at the same time. Um The reason is because A and B genes are codominant. Um therefore, blood group A B can exist. Um oh, on the other hand, is recessive. So it doesn't code for any antigens, whereas the aging codes for a antigens, bag gene codes for B antigen. But um the O doesn't like the O gene doesn't co code for any antigens at all and it's also recessive. So essentially a person with blood group A can have either a A or OA phenotype because either way um A is the one that's dominant and that's what's gonna be expressed. And the person with blood group B can have um BB or OB genotype and a person with blood group O will have to have an O ob genotype because um obviously it's recessive. So you're gonna need two copies of both genes for it to be expressed. And like I said, previously, blood group A B, um the gene type is gonna be A B. OK. So what could happen if someone received a oh incompatible red cells? Um So, a hemolytic transfusion reaction is gonna occur. And what this entails is the patient is likely to undergo fever, experience chills, shock, organ failure, um tachycardia which refers to an increased heart rate and this is in response to all of the like blood that they're losing like your, your red cells are basically just gonna get destroyed and um from shock and to make up for that like um there's gonna be increased heart rate. Um The the patient is also gonna present with jaundice because the liver processes the increased bilirubin from hemolysis. So, hemolysis, when all is when all of your red blood cells are being destroyed. Um when the destroyed bilirubin is produced and due to the um liver processing this bilirubin, um uh patients can uh present with jaundice, um dark urine as well. Again, this is because of the excretion of hemoglobin or myoglobin because remember, hemoglobin has like, this is basically what makes red blood cells red, it has this red pigment which is gonna cause your urine to become darker as well. Um OK. So we went through the A B system. Now we're gonna look at the Rh um rhd system. So the Rh, so the Rh system, uh the Rh blood group system is another key system for classifying blood based on the presence or absence of the Rh antigen. And the main one that you guys need to know is the D antigen um on the sub of uh red blood cells. So RHG positive refers to patients that do have ad antigen on their red blood cells. And this is the most common type. Um About 85% of people worldwide are Rh D positive. Um rhd negative is basically when there's an absence of the D antigen on red blood cells. And this is quite rare only about 15% worldwide. Um R RG negative. Um The Rh factor is inher inherited in a Mendelian dominant recessive manner, like a lot of other um genes. So, unlike the A BO system, this is not codominance. Um So your D gene codes for the D antigen, the recessive gene codes for no antigen on the RBC membrane. Uh So basically rhd, this means that rhd positive can come from either uh capital D, capital D or capital D lower cases. So, um yeah, you can have two different genotypes for this. Whereas rhd negative, the genotype has to be two recessive um um too recessive. Uh sorry. A for uh the, the, for the um the antigen. OK. Anti D antibodies. Um Remember, so if I'm, so if you're gonna have um D antigens with, with the A B system, if you have a antigens in the, on the red blood cell, you're gonna have anti B antibodies and vice versa with group B but with rhd positive, so Rh D positive people have no anti D antibodies in their plasma because again, like that would just make no sense. Um The blood would just agglutinate with rhd. Um they usually don't have anti D antibodies in their plasma either, but they can be sensitized to it. And this can happen in different ways. For example, if they're transfused with um rhd positive blood, for example. So if an RD negative patient is transfused with Rh D positive blood, what happens is the patient recognizes the um D antigens on the red blood cell as foreign and because it recognizes it as foreign, it will make the immune system will start to make anti D antibodies, but nothing's gonna happen this time around. So like the patient is still going to be fine, but in a subsequent transfusion that was also wrong. So somehow the doctor gives you another um another incorrect um blood transfusion and the rhd negative patients get uh Rh D positive blood, again, that's when it's gonna be a problem because the anti D antibodies that were already made last time they attack the uh red blood cells and they basically get lysed so destroyed. And the clinical manifestation of this is gonna be jaundice again because of the buildup of bilirubin from broken down red blood cells. And um also anemia because of all of like this loss of red uh red blood cells. And similarly in pregnancy, it's kind of the same thing. But um what happens is um Rh sensitization is gonna occur when an rhd negative mother is exposed to Rh D positive fetal cells, um uh causing anti D antibody production and in subsequent pregnancies, if the fetus is Rh D positive, again, that's when HD will occur. So, hemolytic disease of the newborn and if this is severe, you can, the um the uh fetus can um present with hydrox fetalis. This is basically severe fetal edema. And what happens, what happens is like it, it kind of just like swells up because all of the red blood cells are being lysed. So, like fluid leaks out of the red blood cells and causes swelling and that's in severe cases. But even in less severe cases, um jaundice can occur and also brain damage. So ultimately, it's yeah, uh it's very unlikely that the baby will survive. Um you could avoid sensitization by basically giving the same blood. So Rh D positive gets Rh D positive and say with rhd negative, rhd negative can be given to Rh D positive. Um but it's just a bit, it's a bit wasteful because like only 15% of people have rhd negative and then 85% have Rh D positive. Like you might as well save the rhd negative for people that actually need. Like other are the Rh negative patients. Um rhd negative must be given to rhd negative. And um so in basically cases of emergencies, what you would uh give to patients is group uh O negative because that's like the universal donor. And yeah, it's given in emergencies if you don't know the um blood group just yet. OK. Another question for you guys. Um This one's a little harder um but list all the A B and R HD group blood cells that would be suitable in the event that this patient requires a blood transfusion. Um I'll, I'll sort of explain how to read this and maybe you guys can have a go, it's quite tricky. But um yeah, I'll give you a bit of time if you don't get it, we're gonna go through it. So um in terms of the areas that have like a small red dot um presume that there's agglutination happening here whereas um areas that have it where it's just like fully red, that's fine. No agglutination has occurred. Um I'll give you two minutes if you guys don't get it, just put it in the chat and we'll go through it together. Um OK. Yeah. I think we'll go through this one because yeah, it is quite a difficult question to get your head around. But the answer for this is um O negative. Uh So you're gonna give them uh um and Rh D positive blood, sorry, did I say O negative? O positive? Um And the reason for this is because um if you look at the diagram, unfortunately, I can't annotate, but if you look at the top left um corner, you know that no hallucination has occurred here because it just, it looks like it's, it's a plain little black circle of red, there's no plotting happening. Um And the forward group is basically um the patient's red cells, you don't know what they are right now, but it's the patient's red blood cells and you're adding anti A antibodies to it. But there's been no hallucination and it's, and, and, and it's completely fine. This means that there are no um a antigens on it for there to be agglutination. Hence, it can't be uh a red cells. It can't be group A because there's no, there's no like reaction with the anti A antibodies, right? And if you look at the circle next to it, um we've got anti B reagent. So the anti B antibodies again with the patient, but with the patients who have blood cells, there's been no reaction. So we can see that um it's not, it's not gonna be group B either because if it was group B, then I would have B antigens on, on the red blood cells and those would react with the anti B antibodies and cause agglutination. And you'd see a small, little like a red.in the middle. So it's not A and it's not B either, which concludes that it's likely to be group O and we can confirm this by looking at the reverse group. So the reverse group is always the, like the patient's serum. Um which means that uh like we're looking at the antibodies in the patient's serum. Um Again, we don't know what they are and we've added uh reagent a red cells. So basically group a red cells to this um to this patient's serum and there has been a hallucination. So if there's um sorry, yeah. So there has been agglutination. So if I was to be group, so I'm being confused and yeah. OK. That confirms that it's group group O because group O means that I'm gonna have anti A and anti B antibodies in my plasma, right? Therefore, there's hallucination because um uh red cells will have a antigens on them which will react with the anti A antibodies in that person's plasma. And again, with reagent B, the B, the um group B red cells will have B antigens on them which then react with the anti B antibodies in the group in the person with group of blood. And so, yeah, that essentially just confirms that So that was like probably badly explained, but that essentially confirms that it's, this person is group O. And in terms of um whether they R HD positive or negative, we can see that there's been agglutination when anti D antibodies were added to their forward group. So their red cells have reacted with the anti D antibodies. And this can only happen if there are anti, if there are antigens, um the antigens on their red cells. Um Therefore, they are Rh D positive. I hope that makes sense. If you guys still have a question, then please put it in the chart or OK, it makes sense good. Um OK, we're gonna look at uh what blood parts are given to you. So, blood transfusions don't just mean that we're giving red cells to the patient, but often in like in cases of anemia, this is the most common transfusion patients are gonna get uh just your red blood cells and nothing else. But um in other cases um where patients are basically presenting with prolonged APTT and PT. So I haven't actually, I haven't actually covered what these are previously. But so um A PTT and PT are laboratory tests which are done to measure the activity of clotting factors that we looked at in hemostasis earlier on. Um And if you look at the note that I written underneath uh prolonged A PTT is seen when there's reduced activity of factors. 89, 11 and 12 and prolonged PT indicates reduced activity of factors, 279 and 10. So this is just something you guys are gonna have to memorize. But um yeah, so fresh frozen plasma is given to patients that are presenting with prolonged A PTT and PT um or to reverse the effects of Warfarin. Um because uh fresh frozen plasma is gonna have all the clotting factors that this person doesn't have or the um the person that has reduced activity of these factors can be replaced using this, using another person's plasma. Um And in terms of reversal of warfarin. So, um like I mentioned previously, Warfarin is like it's an anticoagulant therapy, right? So, um in order to reverse those effects, we can basically give this patient more clotting factors. And um yeah, uh reverse the effects of that. So, cryoprecipitate is um used to replace Factor 813 B WF and Frigen and it's used to treat heavy bleeding. Um platelets can be given to patients with like uh bone marrow, fail thrombocytopenia and heavy bleeding. And D I CDI C is basically disseminated intravascular coagulation. It's just just another, another disorder where there's basically um to, to like um where you need more plats for like clotting to occur properly. Um Factors eight and nine can be given to patients that have um hemophilia A and B respectively. Um I don't know if you guys remember, but um hemophilia A is a deficiency of factor eight and B is a deficiency of factor nine. Um ok. So another question. So a bleeding patient has a prolonged activated partial thromboplastic time, uh APTT and prothrombin time. PT, but a normal platelet count and normal fibrinogen concentration, which is the most suitable blood component for treatment of this patient. Yeah. Correct. So the answer is um fresh frozen plasma. Um But yeah, so that's it guys. That's um the end of the tutorial, we've covered hemostasis, anemias, interpreting FP CS blood groups and transfusions. Um I hope that made sense to you guys and if you do have any questions, um like I said, email me. Um and I'll be happy to get back to you. Um Thank you so much for attending. Yeah. Thank you uh to our speaker. Thank you Ritika. Um And we were playing the links of the recording of the chat as well. Um Any questions just email uh Tica as she said, um I put my email on the chat as well so you can email me if you want. Um But yeah, uh that's the end and we will see you next time. So we've got endocrinology, neurology, and cardiology coming up this year. Uh Sorry, this month um for your BRS uh exams. Um So hopefully we'll see that. Thank you. Great. I see.ac.uk. All right. Uh Yes, there is a feedback form actually, my bad. Um Let me send the feedback form. It's been said on the chat. If you could please fill that in. Um Then that would be great. I'd be much appreciated. Thank you, Paul for reminding me. Uh and uh yeah, thank you.