Blood 3, Blood cells.

all this Bloods just been removed from a radial artery it's therefore been removed from the systemic arterial circulation and as we can see it's 98% saturated with oxygen and this is what we would expect from arterial blood 96% or more saturated with oxygen this means that of all the hemoglobin molecules in this blood that you are looking at 98% of them are carrying the full amount of oxygen that they can carry or to put it another way it means the lungs have been working with 98% efficiency which is really quite impressive when you think about it now the reason the blood is bright red is because it contains oxyhemoglobin it contains a lot of oxyhemoglobin and only a very small amount of deoxyhemoglobin and when the oxygen combines with the hemoglobin this is what gives rise to the bright red color oxygenated blood carrying oxygen from the lungs to the tissues where it is required and this is also important clinically so if you see a wound and you see this bright red blood in the wound that indicates there is arterial hemorrhage going on because the bright red blood comes from the arteries and that might guide your management because it will be a good idea to restrict the amount of arterial hemorrhage well this blood has just been removed from a systemic vein and as we can see is quite a lot darker than the previous bright red systemic arterial sample that we've just looked at the reason it's darker in color is it contains a higher proportion of deoxygenated hemoglobin that is a higher proportion of deoxyhemoglobin sometimes referred to as reduced hemoglobin so when you see this sort of dark colored blood in a wound it indicates that there's venous hemorrhage going on and it's actually quite interesting when we take blood from a venous sample and we put it in our blood gas machine we find that the oxygen saturation is still around about 75% so what this means is that when the arterial blood the systemic arterial blood goes to the tissues is not giving up all its oxygen by any means it's only giving up about 25% of its oxygen and that partly deoxygenated blood is returning to the heart to return to the lungs to be reoxygenate again but when it returns to the heart in the systemic veins and then when it's pumped from the right ventricle of the heart through the pulmonary arterial system it's still about 75% saturated not fully deoxygenated blood consists of two basic components the first is the fluid component referred to as plasma or sometimes referred to as serum and within the plasma floats the second component the blood cells and blood volume is normally made up of about 55% plasma and 45% cells in men in women it tends to be about 60% plasma and 40% cells and even anticoagulants such as heparin is added to a sample of uncalculated blood which is then centrifuged or allowed to settle for quite a while all of the cells will settle out on the bottom of the tube while the plasma remains floating on the top and that is what we see in this picture we can see the clear straw colored plasma at the top and the red cells at the bottom and actually this sample is not that well settled not that well centrifuged because you can see that that volume of plasma is not 55% like it says on the on the annotation but in actual reality it is because this is not fully settled sample and if you look just above the red cells and just below the plasma you can probably see a thin layer of white cells these are the leukocytes or the white cells so this is what you see when you want to coagulate and centrifuge a blood sample the plasma on the top the thin layer of white cells and then the thicker layer of red cells and the persuit the proportion are actually the percentage of blood which is made up of red cells is described as the hematocrit so the hematocrit typically in men will be 44 or 45 percent and in women typically the hematocrit will be round about 40 percent plasma is a yellowish fluid which is about 91 percent water and this keeps the blood fluid so it can circulate freely around the vasculature of the body allowing normal circulation the rest of the plasma is made up of various substances in solution and suspension so it includes plasma proteins nutrients dissolved gases waste products and a lot of the biochemical tests that we do on blood are looking at the biochemical composition of the plasma plasma carries absorb nutrients that have been absorbed from the gut to all tissues of the body which need them is the universal transport system these include nutrients such as glucose amino acids vitamins and minerals the fatty component that's actually absorbed from the gut goes into the like Neels first in the villi and from the lacteals it goes through the lymphatic system and actually drains into the subclavian veins particularly into the left subclavian vein as chylomicrons so it's actually absorbed in a slightly different way but once it's in the blood it's still transported around in the plasma when tissues metabolize protein especially if the protein is deaminated broken down to release energy then that generates waste nitrogen and this nitrogen goes into the tissue fluids and it goes into the plasma and it combines with water and that forms ammonia and ammonia is a very smelly very alkaline very toxic molecule so the body doesn't want ammonia floating around for long so what happens is as soon as the ammonia circulates through the liver the liver takes out the waste ammonia and converts it into urea a new rear is much less toxic but still highly soluble and once formed the urea is transported in solution from the liver to the kidneys and the kidneys incorporate the urea into urine and thereby excreted from the bodily proteins are organic molecules they contain carbon hydrogen oxygen nitrogen and sometimes other elements as well and there are three main plasma proteins circulating with the blood plasma albumen globulin and fibrinogen and the main ones and proteins are very large molecules and so their presence is vital to generate plasma osmotic potential without this osmotic property the blood would be unable to reabsorb tissue fluid into the venous end of capillaries albumin is the most common plasma protein and also generates most of the osmotic potential of the plasma the globulin proteins include the immunoglobulins and you might remember that immunoglobulins are antibodies which allow the body to fight off infection these are the immune proteins and without these we'd probably die of the next viral or bacterial infection that we pick up other globular proteins act as molecules which transport some hormones and minerals around the body fibrinogen is a plasma protein which is essential for the process of normal blood clotting now as fats are not soluble in water they're actually transported around the body bound to plasma proteins and these combinations of fats and protein are termed lipoproteins and they're soluble in water endocrine glands produce hormones the chemical messengers and these are released directly into the bloodstream so endocrine glands have a good perfusion of blood there's lots of blood going through the endocrine glands and when the hormones are released they are released directly into the blood and there they circulate to get to the target tissue where they're going to have some physiological effect so obviously the endocrine hormones are going to be sported in the blood because they're released directly into the blood when they're made transported in the blood to the target tissue where they're going to work the two main forms of blood cell are the red cells or the erythrocytes which is the biconcave disk you can see on the left of this picture the second main group of blood cells are the leukocytes or the white cells and there's an example of one of those on the right and the third cellular component in blood are the platelets or the thrombocytes and these aren't full cells they are cell fragments they derive from large cells called megakaryocytes so they are cell fragments so they are part of the cellular component and they are essential for the process of blood clotting the reason blood is red is because it contains the red blood cells the erythrocytes and the function of these red blood cells is to carry oxygen from the lungs and to the tissue or the tissues of the body and they also carry some carbon dioxide from the tissues back to the lungs to be excreted in the exhaled air now the percentage of blood which is composed of the red blood cells is termed the hematocrit and the hematocrit can be lowered in some forms of anemia and we can see from this picture that the red cells are small by concaved discs and the reason they're red is that they contain the hemoglobin oxygen carrying pigment and each molecule of hemoglobin in the red cells can carry four molecules of oxygen so we see that the red blood cells are biconcave disks and this shape provides a large surface area for gaseous exchange so there's more surface area for the oxygen to get into the red cell compared to its volume it has a large surface area and as well as that some of the capillaries in the body and for example in the kidneys are in the brain are actually smaller than the 7 micrometer diameter of the red cells and they have to deform and squeeze to get through the smaller capillaries and this by concaved shape gives them flexibility so they can deform to squeeze through small capillaries so as we've said the red cells are about 7 micrometers in diameter that 7 thousandth of a millimeter and in normal blood every cubic millimeter of blood every mm to the 3 every cubic millimeter contains about 5 million of these red blood cells so here we see views of a red cell from above on the left and from the side from above the outer thicker layer of the cell is going to appear darker red than the thinner inner layer almost like the middle of a doughnut but it's not a hole there is actual continuation of the cell and the lighter area in the center of the erythrocyte is called the area of central power pala means paleness representing the thinner middle and this should be a third or less of the total diameter of the red cell a wreath Row is the prefix that means red so a wreath Row is red and of course sites are the cells and the erythrocytes in circulation in the bloodstream don't have a nucleus now when they were being formed in the bone marrow there they were nucleated but they lose that nucleus at around about the time they are released from the bone marrow so in circulation they have no nucleus so the red cells are the only sell in the body which has no nucleus they had one in the past but they haven't got one when they're circulating we've said there's about five million per cubic millimeter of blood and they're about seven micrometers in diameter and the reason they're red is because they contain hemoglobin hemoglobin is the actual pigment that carries the oxygen and a single hemoglobin molecule can form a loose bond with four oxygen molecules and although the hemoglobin molecules are large at the center of them they are based on four atoms of iron and so there's if there's a deficiency in the diet of iron if people do not get enough iron to eat then the hemoglobin can't be properly synthesized and they can get anemia so the mature red blood cells circulating in the blood are unique because they don't have a nucleus and this is good because it allows more space for carrying more hemoglobin and therefore increases the oxygen carrying capacity of the cell but it also limits the lifespan of the cell because the cell is not able to repair itself because it's not carry the genetic material from the DNA in the nucleus and for this reason they have a limited lifespan around about 17 weeks or 120 days but these are absolutely vital the red cells in the lungs the dark red deoxygenated hemoglobin will combine with oxygen to form the bright red oxyhemoglobin and in the systemic capillaries the reverse will happen oxyhemoglobin will give up the oxygen molecules and revert to being deoxygenated again so in a sense the hemoglobin molecules are like little trucks they carry oxygen from the lungs and they drop this oxygen off in the tissues and it's the color change which accounts for the bright red blood seen in systemic arteries as opposed to the dark red blood seen in systemic veins the erythrocytes are formed from blood stem cells found in the bone marrow and this process is called a wreath rope oesis and the red bone marrow is found in flat bones for example in the bones of the skull the bones of the sternum the ribs the pelvic bones red bone marrows in the flat bones and it's also at the ends of the long bones in the epiphysis the end part of the long bones so thinking about bones like the radius and ulna humerus femur tibia fibula all have red bone marrow in the ends of the bones and these contain the stem cells to make the new blood cells and a stem cell is any capable any cell which is capable of differentiating into other cell types now the end of the lifespan the old red cells are phagocytosed by large cells called macrophages they're eaten up and digested by macrophages and this is good because it means that the proteins which were in the old red cells can be recycled again so it's quite an efficient process and this process takes place mostly in the spleen because there's lots of macrophages in the spleen but it also takes place in the liver and the bone marrow to some extent so the proteins from the old red cells are broken down into amino acids and the iron from the hemoglobin from the old red cells is transported back to the bone marrow to be recycled to make new red blood cells so there's no waste in this process but there is a colored pigment from the hemoglobin that's not broken down and this is converted into the bile pigment called bilirubin which is taken up by the liver and excreted into the small intestine as a component of the bile and of course bile is useful because it emulsifies fats and it colors and deodorizes to some extent feces well the reason that the red cells are red is because they contain this red iron-containing pigment called hemoglobin and this is the oxygen carrying molecule in the erythrocytes and because it's a combination of protein and iron protein in a metal it's called a metalloprotein so it's the oxygen transporting metalloprotein and actually it also carries about 10% of the carbon dioxide which is produced in the tissues back to the lungs as well in the form of carbon Ino hemoglobin so carb amino hemoglobin is when the hemoglobin is combined with carbon dioxide but of course when normally thinking about hemoglobin is carrying the oxygen the deoxygenated hemoglobin becomes oxygenated and forms the bright red oxyhemoglobin and typically in the systemic arteries we're going to get saturations of 96 to 99 percent although it can easily go up to 100% if you take a few deep breaths now someone's once calculated that there's 640 million molecules of them hemoglobin in a single red blood cell and I'm not quite sure how we counted them that's what they say 640 million molecules of hemoglobin 4xl and hemoglobin is is an impressive molecule as well as carrying the oxygen it can collect the oxygen and it can give it up very quickly so when the oxygen is traveling through the oven the red cells rather a traveling through the pulmonary capillaries the oxygen comes into them really quickly in about a hundredth of a second the hemoglobin molecules can oxygenate as the blood passes through those pulmonary capillaries so men typical hemoglobin values as we see here 13 to 18 grams of hemoglobin per hundred mils of blood women are a little bit less and one molecule of hemoglobin is going to carry four molecules of oxygen and this means that in normal levels of hemoglobin 100 mils of blood can transport 20 mils or oxygen so it's the red colored pigment in the red cells carries the oxygen it's what makes the blood red hemoglobin which is not carrying oxygen is sometimes called deoxyhemoglobin or reduced hemoglobin it's the same thing and this hemoglobin has the potential to loosely bind or bond with molecules of oxygen and as we've said each hemoglobin molecule can carry four molecules of oxygen and this forms bright red ox hemoglobin in the lungs and this bright red oxygenated blood is going to drain via the pulmonary veins into the left atrium of the heart so the pulmonary veins are carrying this oxygenated blood into the left atrium down into the left ventricle when the left ventricle contracts the blood is going to be pumped out into the aorta and into all of the systemic arteries of the body the systemic arteries are going to feed the blood to the arterioles and that's going to feed blood into the capillaries and it is the capillaries which are the actual site of gaseous exchange in all the other blood vessels the walls are too thick for there to be any significant gaseous exchange taking place so in the tissues the oxyhemoglobin will dissociate releasing the oxygen which will diffuse through the wall of the capillary into the tissue spaces into the cells to supply the cells specifically to supply the mitochondria to facilitate the process of respiration in those cells that will leave the deoxygenated hemoglobin or partly the oxygenated hemoglobin at the venous end of the capillary that will then drain into venules into systemic veins into the inferior and superior vena cava which drain back into the right atrium from the right atrium the blood will go through the tricuspid valve into the right ventricle it will be pumped out of the right ventricle into the pulmonary arteries and go to the pulmonary capillaries and again it is the pulmonary capillaries where the processes of gaseous exchange take place they're the only vessels where the walls are thin enough so carbon dioxide will pass from the blood that's derived from the pulmonary artery into the public a pillow is the carbon dioxide will pass from the blood into the alveoli an oxygen will pass from the alveoli into the blood then again the blood will drain from the lungs in oxygenated form going back to the left atrium completing the circulation of blood with the oxygenation and deoxygenation of the hemoglobin molecules now in the arterial blood you might find that the oxygen saturations are 97 98 % something like that you take a few deep breaths can easily go up to 100% and in the veins the oxygen saturation goes down typically to about 75 percent so it's not that the hemoglobin is completely reducing as it goes to the tissues it's only losing about 25% of its oxygen and it's going to the lungs to be topped up again so typical oxygen saturations in systemic arteries are going to be in the high 90s typical oxygen saturations in the systemic veins therefore the oxygen saturations in the right side of the heart and in the pulmonary arterial system are going to be in the order of 75% saturations leukocytes are the white blood cells luke means white sites cells and their basic function is to protect the body against infections and infectious disease and this will include resistance to bacteria viruses fungi protozoa parasitic worms and indeed some toxins as well some leukocytes will also attack and kill some cancer cells and they also unfortunately defend the body against transplanted organs and this is because white cells are able to distinguish between self and non-self material and they will attack anything they perceived to be nownself not part of the body the white cells are much less numerous than the red cells each cubic millimeter of blood contains about 7,000 leukocytes now there are two main forms of white cells which are described according to the appearance of their cytoplasm some white cells have cytoplasm which appears granular so this group are classified as a granular sites other white cells have cytoplasm which appears clear with no obvious granules and these are called a granular sites a or an of course means without so these cells are without granules of course this is a very simple way to look at things and it's based on classification using light microscopes it's what you would see with an ordinary light microscope there are three main types of granular sites and these all end in phil neutrophils eosinophils and basophils so the fills are the classic granulocytes and there were two main forms of a granulocytes lymphocytes and monocytes however the thrombocytes that is the platelets are also normally included in this group of a granular sites with the lymphocytes and the monocytes now this graphic is designed to give us an overview of the structure of the blood so the top we seen as the blood divided into cells and plasma and we can see the water contained in the plasma and protein contained in the plasma nutrients hormones waste products are in solution in the plasma so that's the fluid component then as we go to the left we see that the blood also contains cells and we see that this is red cells which are the erythrocytes and also white cells so the white cells can be divided into granular sites and these are the ones that end in film so the basophils neutrophils and eosinophils or the granule sites and it can the white cells the leukocytes that is leukocytes and white cells are exactly the same thing they can also be divided into a granular sites cells which with the light microscope did not have obvious granules in their cytoplasm although they do with the agent of electron microscope but what we call the a granular sites are divided into monocytes lymphocytes and the thrombocytes are the platelets and when the monocytes migrate into the tissues we start to call them macrophages but the lymphocytes themselves are divided into large and small lymphocytes the large lymphocytes are the natural killer cells the NK cells and the small lymphocytes are divided into B and T lymphocytes and the T lymphocytes are themselves subdivided into helper cytotoxic and suppressor T cells so it's the role of the B lymphocytes the small B lymphocytes to synthesize the immunoglobulins to make the antibodies that combat infection in the process of acquired specific immunity and the T cells stimulate this process and the suppressor cells say when this process has been carrying on for long enough they limit the length and magnitude of the immunological response when the cytotoxic cells are capable of directly killing cells and they can kill cells which are infected with viral particles and very often they can kill malignant cells as well so it's a scheme attact to give us an overall feel for the components of the blood well it's important to remember that the white blood cells were named in the days of light microscopes only where it wasn't possible to get that much microscopic detail on what we were looking at in the cells so at that time some cells were described as being a granular sites and this means they did not have obvious granules in their cytoplasm so they were a granular sites a meaning without so the cells that were without granules or at least a pairing granules on light microscopy but there are other types of cells that were called granular sites and there's three main types of granular sites neutrophils eosinophils and basophils and we notice that all of these granular CITIC leukocytes all of these types of white blood cells end in phil will be looking later on at the two main forms of a granular sites which is the lymphocytes and the monocytes however on this slide we are looking at the granular sites and I think we can notice that the neutrophils have got the smallest granules then the eosinophils tend to have bigger granules and the basophils have the largest granules of all now there's very few basophils actually that you will see on blood slides most of them seem to migrate into the tissues where they form the mast cells so the granular size remember neutrophils eosinophils basophils they all end in phil well if you start looking at blood slides it would take you quite a long time to come across one field where there's four neutrophils in view because the neutrophils of course are very much less common than the erythrocytes than the red cells but I think you can clearly see the red cells in this picture and you can see the area of central power in many of the red cells that is much thinner than the area around about the outside of the cell and also we can see some small blue stained cellular fragments dotted around this picture these are the thrombocytes or the platelets that we can see but I think you can see from this why neutrophils are sometimes called polymorphonuclear cells poly means many more shape there are many shapes in the nucleus typically three or four so for example this cell on the bottom left we can see the lower left neutrophil we can really see that there are three lobes in the nucleus joined by nucular strands and actually as the cells get older they can grow more lobes in their nucleus so an old neutrophil may we'll have five lobes in its nucleus so we can see that they are polymorphonuclear cells now the neutrophils are the most common form of leukocyte that is the most common form of white blood cell normally comprising about 60 to 70 percent of the leukocytes in the blood and most of the granules in the cytoplasm are fairly small and actually might be difficult to see under a light microscope and the granules in the cytoplasm contain enzymes such as lysozyme and other enzymes which are capable of digesting bacteria in the process of phagocytosis so these neutrophils are capable of phagocytosis in bacteria and dead body cells and the nucleus of a neutrophil has two to five lobes as we've said so it can be as little as two when the cell is young connected by fine threads so they're sometimes called polymorphonuclear sites now the key thing is during an infection the number of neutrophils will increase significantly because it is the neutrophils that help the body fight off the causative organisms of the infection and this is particularly the case with bacterial infections and this increase in number of the neutrophils is called a neutrophil leukocytosis an increase in the number of white cells is a leukocytosis and as well as killing bacteria neutrophils can kill fungal infections as well and in addition they'll phagocytose dead or damaged body cells so when body cells are killed in a disease process or as a result of injury it's important that they are phagocytose and removed this means the amino acids and the cellular and the chemical components they are composed of can be recycled to make new tissues which is good but if they're left in the tissue they'll form what's called necrotic areas of dead tissue and these will supply food and habitat for bacteria increasing the likelihood of infection and neutrophils migrate out of inflamed blood vessels into areas where there's injury or infection to perform these immunological functions so if there is an inflamed area the neutrophils will be able to migrate out of the capillaries into the tissue where they can phagocytose dead tissue cells where they can phagocytose infecting bacteria thereby providing a vital immunological function so if you find that the number of neutrophils has increased greatly in the blood this may well be because there is a bacterial infection now the eosinophils are often slightly larger than the neutrophils maybe 13 to 15 micrometers in diameter and the cytoplasmic granules in eosinophils are larger than those seen in the neutrophils and normally only about between two and four percent of the leukocytes in the blood are eosinophils the nucleus in an eosinophil normally has two lobes although looking at this one it appears to have three but the lobes are joined by a thin nuclear thread and eosinophils help the body fight infections of protozoa so you might think of amoebic infections for example like me big dysentery or amoebic liver abscesses the eosinophils help fight the protozoa these large eukaryotic cells that are parasitic and eosinophils also fight larger parasitic worms and other parasites as well and if a parasite enters the body yo sinner fills attach themselves to the surface of the parasite and stick to it using adhesion molecules and they then deposit digestive enzymes and other toxic molecules from the granules inside the eosinophil onto the parasite and these granules contain digestive enzymes and other nasty things that the parasites don't like and this toxic assault from the eosinophils will weaken or kill the parasite reducing the damage is able to inflict on the body and hopefully reduce its ability to reproduce and eosinophils are also attracted to areas where allergic reactions are occurring such as in the bronchioles in people suffering from asthma and once in the area where the allergic reactions going on they're able to chemically neutralize and detoxify some of the inflammation causing substances such as histamine which are involved in the generation of the allergic inflammatory response and this is why ESC eosinophils increasing parasitic infections and in allergic disorders and many eosinophils migrate out of the blood to protect tissues against protect potential infections and this often happens where body surfaces are exposed to the internal to the external environment so we can get bacteria and things on the external environment and this is why a sinner fuels can be found in association with mucous membranes in the digestive and respiratory tract as well as in the female reproductive tract and if there's an increase in the number of eosinophils we will call that an eosinophil e'er and it was an eosinophil e'er this can indicate parasitic infection amoebic infection or allergic reactions as such as asthma the basophils are the least common of the leukocytes only half a percent or less of the leukocytes will be basophils and the nucleus is irregular and lobed but it's often hard to see the nucleus because there's so many large abundant granules in the cytoplasm they obscure your view of the nucleus now the granules in the basophils contain histamine heparin and braddock einen and the physiological role of basophils in the blood is not particularly obvious but it is well known of course the heparin prevents blood coagulation because it's an anticoagulant but most basophils actually enter the tissues where they remain localized and in the tissues they're called mast cells and their main function is to facilitate inflammatory reactions in response to insults of the tissues by releasing their histamine and these other inflammatory mediators into the tissues so if a tissue is damaged the mast cells will release inflammatory mediators and this will generate the inflammatory response that we normally expect to see heat pain redness swelling and loss of function so here we see a basal fill that's migrated into the tissues and when they migrate into the tissue they changed their name they're no longer basophils they become mast cells so really what we're looking at here is an X above ever fill now called a mast cell now these tend to stay in the same tissues for long periods of time and they facilitate inflammatory reactions and especially they can generate allergic inflammatory type reactions so on the cell on the right here we can see the nucleus and we can see they're very large granules containing the histamine and the heparin and the bratty Kynan and when the cells stimulated to release these inflammatory mediators it's almost like the whole cell falls apart it granulates lordi granulates rather so in the picture on the top left we can see the granules D granulating and they all fall out of the cell locally releasing these inflammatory mediators bring about a localized inflammatory reaction and from this graphic in the top left it almost looks like the cell would die as a result of this it seems to be falling apart but it doesn't it releases the granules in this d granulation process and then the cell will survive and recover again after this so the mast cells were basophils but they now live in the tissues as mast cells leukocytes are the white blood cells and the leukocytosis is a significant increase in the number of white blood cells in the blood and as we know it's the leukocytes that are involved in immunological function so if there's an increase in the number of neutrophils this indicates bacterial infection because the neutrophils combat bacterial infection for example they can phagocytose them and an increase in the number of neutrophils would be a neutrophilia indicating a bacterial infection because the number of neutrophils would increase as the immune system seeks to combat the bacterial infection an eosinophil e'er would be an increase in the number of eosinophils indicating parasitic infection amoebic infection or disorders such as asthma basophils form mast cells and if there wasn't increase in number of basophils that would be called basophils but that's not clinically common situation now if there is an increase in the number of monocytes that would be a monocytosis and as we'll see shortly the monocytes are involved in combating chronic bacterial infections such as tuberculosis so in tuberculosis you would expect a degree of monocytosis and the lymphocytes are there to combat primarily viral infections by making antibodies so a lymphocytosis would probably indicate viral infection particularly and this is why we do differential white cell counts yes we're looking for a leukocytosis but is it a neutrophilic leukocytosis or is de lymphocytic leukocyte osis because these would indicate different sorts of likely etiological infections remember that there's basically two forms of lymphocytes there's large lymphocytes and there are small lymphocytes the large lymphocytes are the natural killer cells that will kill cancer cells that will kill cells infected with viruses with viral particles the natural killer cells but the small lymphocytes can be B or T type and lymphocytes and this is a small lymphocyte that we're looking at here by looking at it I can't tell whether it's a bee or a tea type lymphocyte but it is a lymphocyte so the large lymphocytes are the natural killer cells in this picture we see one of the small lymphocytes that can be B or T lymphocytes but I don't think you can tell the difference by looking at them it's more a chemical sort of difference or histological type of difference between the B and the T cells but the lymphocytes are the most common form of a granulocytes normally making up about 20 to 25% of the circulating leukocytes and most of the lymphocytes are classified as small and you can see they are quite small they're not a lot bigger really than the red blood cells which are surrounding it and you can also see some platelet fragments off to the right there the thrombocytes the smaller cell fragments and the nucleus in the lymphocyte is large and fairly spherical and large numbers of lymphocytes can be found in lymphatic tissue such as the spleen the lymph nodes the tonsils and the appendix and there's two main forms are smaller than four sites there's the B lymphocytes and there is the T lymphocytes and the difference is that the B lymphocytes mature in the bone marrow while the T lymphocytes mature in the thymus gland and the function of the B lymphocyte B lymphocyte cell lines is the production of antibodies these are the immunological proteins the immune proteins produced in response to the presence of specific antigen in the process of acquired immunity and an antigen of course is something the immune system recognizes as being foreign such as a measles virus so the lymphocytes are making antibodies in response to exposure to antigens they are making antibodies which are immune proteins the immunoglobulins that will combat antigenic infections such as viruses or such as bacteria on this slide we notice a neutrophil on the left and with a large purple stained nucleus we see a large lymphocyte one of the natural killer cells and having said that the lymphocytes are a granular sitting cells we can see granules in the cytoplasm of this lymphocyte now this doesn't actually change the classification still technically lymphocytes are classified as a granular sites but they still have granules in their cytoplasm that contain digestive enzymes and things that can destroy virally infected cells or malignant cells so the large lymphocytes are somewhat granular and they are the natural killer or the NK cells so to summarize the lymphocytes the lymphocytes can be large lymphocytes or there can be small lymphocytes the larger lymphocytes are the natural killer cells and the smaller lymphocytes are the B and the T lymphocytes it is the B lymphocytes that synthesize the immunoglobulins that is make the antibodies and T helper cells T suppressor cells and T cytotoxic cells are the three subdivisions of the T love sites and we've said there's a lymphocytosis that can indicate viral infections so there's an increase in the lymphocytes that can be viral infections for example you might get a lymphocytosis in viral hepatitis but you could also get it in measles mumps toxoplasmosis and some chronic infections as well so it's not necessarily viral infections there's other possible causes of the lymphocytosis now when there's an infection this means that foreign material will enter the body and on the surface of this foreign material there are particular molecules that the immune system recognizes as being fallen and these are called epitopes and there's many millions of different types of foreign material epitopes can be introduced into the body and many types of infection and you have individual B lymphocytes that recognize different antigenic epitopes type molecules and when a small group of the B lymphocytes that recognize a particular antigen it molecule bind to that molecule when that molecule is present when the antigen is present that antigen will bind to molecules that recognize the antigen recognize the epitope on the surface of the B cell and what the B cell will then do once it's recognized the antigen is that B cell will divide many many times this is a process called clonal expansion so a clone is something with the same genetic material so this stimulated B cell that stimulated by the presence of the antigen will divide many many times producing a huge population of B cells all identical that means you get a huge population of B cells that can recognize this foreign antigenic epitopes and will produce the immunoglobulins that are specific to countering that particular infection this is a specific acquired immunity and the huge population of b-cells that derive from the original stimulated b-cell the factories if you like for the antibodies are the plasma cells so millions of plasma cells will be produced that are all identical they'll produce the same antibody that is the immunoglobulin that antibody or immunoglobulin will then counter the infection and eliminate the infection and this is cellular immunity because it's the plasma cells which are the descendants of their ancestors the original B cells that are producing all these immune proteins to get rid of this infection that's been introduced into the body so when there's an infection when we're making lots of antibodies to counter an infection you'll get populations of these plasma cells giving rise to a lymphocytosis and increase in the number of lymphocytes and then when the infection has gone was note there's no need for all these plasma cells producing lots and lots of antibodies so the population will greatly reduce again but there will be a few thousand B memory cells left and these will stay in the circulation probably for the rest of the life of the individual in many cases and that means if the individual is exposed to that infection again they'll have several thousand memory cells that can start dividing into another population of plasma cells really quickly if the antigen is experienced again so that means that a secondary immune response can be mounted much more quickly than the primary immune response and indeed with these secondary immune responses people can be exposed to the antigen for a second time and the antibody response due to the plasma cell clonal expansion is so rapid they don't even realize that they've been exposed to the antigen and don't get sick at all so plasma cells absolutely essential for producing large volumes of immunoglobulin to counter specific infections so here we see that there are two main classifications of small and for sites the B and the T and there are three forms of T lymphocytes and these are T helper lymphocytes T cytotoxic lymphocytes and T suppressor lymphocytes so these different sorts of T lymphocytes now the T helper cells help the b-cells or stimulate the B cells to produce antibodies so it's only the B lymphocytes that will produce the antibodies but they will only do so when stimulated to do so by a T helper cell and this is why HIV human immunodeficiency virus can cause acquired immunodeficiency syndrome aids because the H I virus the human immunodeficiency virus invades and kills T helper cells and this means that they are unable to stimulate the B cells to produce the antibodies and without the antibodies the person becomes immunodeficient now as well as stimulating immunological responses it's also important that the degree of the immunological response can be regulated so when B cells have produced enough antibodies to deal with a particular infection the T suppressor cells inhibit the B cell lines and an antibody production will therefore be reduced and this is important if you think about things like autoimmune diseases where the immune system will attack the body's own tissues which is not at all what we want now the t cytotoxic cells have got a range of defense functions also they're able to detect and kill cells which are infected with viral particles now although it might sound a bit drastic for the body to kill its own cells if a cell is infected with viral particles it will kill the viruses inside the cell and so prevent them from infecting fer the cells and cytotoxic T cells are also able to detect and kill some cancer cells so it may be that malignant cells arrive fairly frequently in the human body who knows maybe every day we develop cancer but God willing we won't get that condition because the cytotoxic T cells will recognize it at the one or two cell stage and then eradicate the malignant cells before a tumor can be formed and T cytotoxic cells can also attack phone material directly such as parasites in a similar way to that we've already learned that the EO cinephiles can do and if there's a number and give this increase in the number of the lymphocytes this is a lymphocytosis and this will mean that more antibodies have been produced to counter an infection normally caused by a viral infection but it can occur in other infections such as tuberculosis often with an increase in the number of monocytes as well so a lymphocytosis we're thinking about infection probably a viral infection but also possibly some source of bacterial infection this picture shows the amazing complex nature of the external cell membrane surface of the t lymphocyte with a light mode microscope you really don't get any idea of this level of complexity and this healthy T lymphocyte will help the B lymphocytes to produce antibodies so here we see one of the large monocytes with their typical kidney shaped large nucleus and these are classified as a granular sites but with good microscopes these days you can actually see small granules in the cytoplasm so they are large phagocytic cells and if they start eating things they can grow to being very large indeed even larger than this one that's shown here so typical kidney shaped nucleus and the key thing about the monocytes is that especially if the capillaries are inflamed they can migrate through capillary walls and then in the tissues they can move around by this process of amoeboid movement so they can patrol through the interstitial spaces and amoeboid movement involves the flow of the cytoplasm within the cell rolling the cell forward and once in the tissues monocytes change their name and they become macrophages and if any bacteria or viruses are encountered in the tissue they will be rapidly destroyed by this process of cell eating the phagocytosis so in the tissues they become macro sites macro means big and phage means to eat so they are macrocytic big cells macrophages big eaters so in the tissues will call them macrophages literally big eaters and the number of monocytes is particularly likely to increase with chronic bacterial infections giving rise to a monocytosis well here we see a macrophage that has been actively eating by this process of phagocytosis and as we can see it's become positively huge you can see just next to it the ordinary sized red blood cell with its area of central power to give us a sense of scale of how big this macrophage has become and the macrophages are derived from monocytes and the thing about the macrophages is they're found in body tissues and indeed there are some macrophages in most body tissues sometimes the fix to tissue cells and sometimes they patrol around a tissue and once in a tissue the macrophages can live for many years just waiting in case there's an infection or they need to perform some immunological function so the macrophages are one of the first lines of defense there in the tissues just waiting in case there's a problem that needs their attention and they'll phagocytose infecting viruses bacteria and they'll also phagocytose necrotic tissue which might have been killed as a result of trauma or infection or a disease process that's good because you don't want a necrotic tissue left lying around in the tissues because bacteria can eat the necrotic tissue as a metabolic substrate and also the necrotic tissue is a good habitat for bacteria to live in so it's best to get rid of it and as well as that healthy cells can't migrate effectively over necrotic tissue so for many reasons it needs to be got rid of and the macrophages will do that by phagocytosis now as well as directly phagocytosis any invaders any viruses or bacteria that the macrophages themselves come across they're even much more clever than that because they can release chemicals called cytokines so if an infection is encountered they'll release a chemical messenger called a cytokine and the cytokine will circulate to the bone marrow where it will increase the release of neutrophils and other immunological cells to help fight the infection on monocytes also produced pyrogens which act on the hypothalamus to increase body temperature during infections and these functions mean the tissue macrophages act as an early warning system and they can initiate localized inflammatory responses and the systemic inflammatory response syndrome as well and the monocyte macrophage cell system is in the body used to be called the reticulo-endothelial system so the monocyte macrophage cell system is the term used to describe all of the monocytes fixed and mobile macrophages in the body and we used to call that the reticulo-endothelial system we now call it the monocyte macrophage cell system well here we see a macrophage actively phagocytosis now these long strings that look like strings of pearls are actually bacteria now a cocci means that the bacteria is round so we can see there's lots of individual round bacteria here so we know we're dealing with a cocci and the bacteria that occur in strips like this are streptococcus so what we see here is lines of streptococcus this is how streptococcus appears it occurs in these long strips and the macrophage is actively phagocytose in them taking them into its cytoplasm once the bacteria are in the cytoplasm of the macrophage they will be surrounded by membranes from lysosomes and digestive enzymes will chemically digest and dissolve away these bacteria thereby killing them and we also see a fairly good sense of scale on this picture so five micrometers is that line along the bottom so we can see that the macrophage is about what 10 15 maybe 12 micrometers across and maybe 20 micrometers long and we can also see the individual scale of the bacteria these look like they're about half a micrometer in diameter maybe a little bit more so once the bacteria have been consumed into the cytoplasm of the macrophage by phagocytosis lysosomes containing lysozyme and other digestive enzymes will fuse with that vacuole and will digest the bacteria now monocytes as we've said can differentiate into macrophages but they can also differentiate into cells which develop rather strange shapes so here we see this one a spread itself out maybe it's trying to detect some antigens it's covering a large area where it could detect possible infecting bacteria or viruses now as monocytes change in the tissues they could become macrophages as we know but they can also differentiate into dendritic cells and dendrite mines branched so here we see these dendritic cells have many branches they're putting tentacles out all over the place and this is that you can cover quite a large area and can detect any antigens in that area and for this reason they act as antigen presenting cells and then if they come across an antigen they will take it in and process it and they will present that to the T cells which will then initiate the cellular immune response so they're detecting antigens in the tissues that is infections in the tissues go into the lymphatics and in forming the lymphocytes that it's time to mount a specific acquired immunological response a PCS antigen presenting cell having first detected the antigens of course they then present them now if we stain specifically for these differentiated monocytes which are now dendritic antigen presenting cells we can see that they are guarding numerous body tissues so here for example we're looking at the epidermis you can see the packed tight cellular structure of the epidermis and the dark staining cells there are the dendritic cells that are positioned in the epidermis to detect any antigens that is any infection getting into the epidermis the top layer of the skin and below this we can see the dermis which is the lower layer of the skin we see there are less cells in the dermis because it contains more extracellular materials such as collagen and elastic fibers but we can also see that dotted around just in case we have these dendritic cells ready to present antigens to detect antigens and then present them to the immune system to generate an immunological response so amazingly detailed intricate defenses against the possibility of infections well you've got to look at quite a few microscope slides to get a nice picture like this we can see the red cells we can see the small cellular fragments which are the thrombocytes or the platelets on the left we can see the polymorphonuclear site the neutrophil then we can see the lymphocyte with its large nucleus in the center and then we can see the monocyte large cell with a large single nucleus so the three main types of a beaver site there or present on one rather nice photograph now in the circulatory system of course it's absolutely vital that blood is a liquid but if there's a cut we want that blood to clot to block off the hole in the vascular system otherwise the liquid blood would simply keep running out and here we see these yellow strands that are fibrin now the fibrin is precipitated out of a soluble protein the plasma called fibrinogen and when it precipitates out it forms these long sticky strands like a network and the red cells will stick to that and in this shot we even see a white blood cell sticking to that or being clotted together by the fibrin mesh forming a blood clot to prevent excessive hemorrhage here's another nice picture of a blood clot we can see the red cells the fibrin strands and a couple of white cells thrown in there for good measure well here's my diagrammatic rather simplified representation of a blood clot but we can see it as a neutrophil we can see this in red cells and we can see that they're held together by fibrin strands now coagulation of blood or clotting of blood is a complex process and there are 12 main factors involved in the plasma and that's why we can see the x11 which is the Roman numeral of course 412 we normally use Roman numerals to indicate the clotting factors so for example you might have heard that hemophilia is deficiency of factor 8 I'm not going to go into it here but you can see that we need platelet-derived factors activated clotting factors calcium and that will convert a protein which is made in the liver called prothrombin into thrombin and when there's activated thrombin around that more convert fibrinogen which is a soluble protein into these strands of fibrin which is precipitated out insoluble and sticky to which the other cells stick to and vitamin K is required for the synthesis of proton beam and fibrinogen well here we see a neutrophilia and increase in the number of neutrophils in the blood as the body responds to an acute infection in this slide we see an increase in the number of lymphocytes a lymphocytosis and if there's too many lymphocytes this might indicate viral infection like hepatitis as we've said could be infected mononucleosis measles could even be tuberculosis but very commonly it's a viral infection causing the lymphocytosis well we see two monocytes here together and we don't see enough of the blood field to decide if this is indeed a monocytosis or just a rather fortunate shot but monocytosis could occur in a infective mononucleosis Hodgkin's disease chronic bacterial infections such as tuberculosis and other long-term bacterial infections typically now in this shot we see an increase in the number of eosinophils an eosinophil iya an increased number of eosinophils in the blood and this could be caused by allergic reactions such as a well asthma could cause this parasitic infections as the body responds to parasites and possibly in some cancers as well an eosinophil iya to many eosinophils leukocytes now here we're looking at a relatively large blood field and I can only see one solitary leukocytes in the whole field there's only one neutrophil here and this is a neutropenia a lack of neutrophils and sometimes this is referred to as an a granulocytes as well a lack of granular sites in the blood and this could occur in some viable infections or tuberculosis or it could occur in systemic lupus erythematosus or rheumatoid arthritis possibly in a plastic anemia sometimes it occurs secondary to administration of cytotoxic drugs or indeed anything which was the person sufficiently depressed the bone marrow and it could be adverse reactions to drugs an account of white cell count of less than one predisposes to infections and a white cell count of less than noir point five predisposes to potential life in life-threatening infections so definite lack of neutrophils here in this neutropenic slide well here's a few normal hematological values you do see slightly different quotes by different laboratories depending on who's conducting the assays but this is a rough guideline as to some normal hematological values well I think with concluded or with given evidence in this slide show so shown that look is essential for the life of every creature thank you for watching and listening

Channel: Dr. John Campbell

Views: 25,118

Rating: 4.911602 out of 5

Keywords: blood, red cells, white cells, erythrocytes, leucocytes, thrombocytes, plasma

Id: UobXCIsmzHA

Length: 82min 9sec (4929 seconds)

Published: Sat Mar 14 2015