BLOOD Function of Blood Single cell organisms, such as an amoeba, live a fairly independent life. However, cells that are part of a larger organism require blood to perform various specialised functions as they cannot, for example, move away from toxic areas, find their own food etc. Blood therefore: transports oxygen from lungs to tissues transports carbon dioxide from tissues to lungs transports nutrients from digestive organs to cells transports waste products from cells to kidneys, lungs and sweat glands transports hormones from endocrine glands to cells regulates body pH regulates body temperature regulates water content of cells prevents body fluid loss protects against toxins and microbes Composition of Blood Blood, which makes up ca 8% of our body weight (4-6 litres), is not a homogenous substance. Its various components can be separated in a haematocrit formed by centrifugation. It is composed of; 1. Plasma (55%) 2. Formed Elements (45%) a) b) c) Erythrocytes (red blood cells) Leukocytes (white blood cells) i) Granulocytes Neutrophils (62%) Eosinophils (2.3%) Basophils (0.4%) ii) Agranulocytes Lymphocytes (30%) Monocytes (5.3%) Thrombocytes (blood platelets) Blood Plasma This is 91.5% water. The rest is solutes, most of which are various plasma proteins (e.g. albumins to create capillary osmotic pressure, globulins to act as carrier molecules and antibodies, fibrinogen involved in clotting). Other things dissolved in the plasma include; hormones, nutrients, respiratory gases, waste products, and electrolytes. 1 Red Blood Cells (Erythrocytes) These cells, which compose 99% of the blood’s formed elements, are anucleate biconcave discs, that can change their shape to ‘squeeze through’ capillaries. The average male has 5,200,000 erythrocytes mm-3 of blood, while females posses on average 4,700,000 mm-3. These very high densities vary depending on a number of factors such as; age, height you live at, and of course your state of health (too few = anaemia) The major function of red blood cells is to transport oxygen. Each erythrocyte contains around 280 million molecules of haemoglobin for this purpose. Every molecule of haemoglobin is composed of a globin portion bound to 4 haem groups. Oxygen binds to the iron (Fe) of each haem group (thus each rbc transports ca. 1 million molecules of oxygen from the lungs to the tissues). We will talk more about this is the respiration lectures Haemopoiesis is the formation of blood cells. In the adult this occurs from stem cells in the red bone marrow which is found in the flat bones of the body (pelvis, skull, clavicles etc.). Since there are many types of blood cell, the question is, how many stem cells give rise to these different types? There are 2 extreme possibilities; 1. 2. One stem cells gives rise to all blood cell types (monophyletic), or Each type of blood cells has its own stem cell (polyphyletic) The answer is in between. There are two classes of stem cell; one giving rise of lymphocytes and the other to all other types of blood cell . Haemopoiesis is thus a limited polyphyletic system. There are 5 phases to the development of every blood cell type. 1. 2. 3. 4. 5. Commitment of the stem cell Proliferation Differentiation Maturation Release The formation of red blood cells (erythropoiesis) shows all these phases. Erythrocytes survive ca. 100120 days. Thus, around 5x1011 rbcs are destroyed every day by the spleen . 2 The stem cell, known as a haemocytoblast, commits to becoming a rbc and develops into a proerythroblast (diameter 14-17 µm), which has a large nucleus occupying about 80% of the cell’s volume. The cell then develops its proliferative phase, forming an early (basophilic) erythroblast. Eventually this results in a late (polychromatic) erythroblast in which the cell differentiates through haemoglobin synthesis. Then the cell matures into a normoblast, in which the nucleus only occupies 25% of its volume, before finally ceasing haemoglobin synthesis and extruding its nucleus. The resulting reticulocyte is released from the bone marrow. Unusually, however, it is still immature and must circulate in the vessels for ca. 3 days before becoming fully mature. Any condition which results in less oxygen being delivered to the tissues (i.e climbing a mountain) causes the release of erythrogenin from the kidney. This converts one of the plasma proteins to erythropoietin (EPO), which acts on the bone marrow to enhance erythropoiesis. Blood can be classified as belonging to various blood groups depending on the presence of antigens on the surface of red blood cells. Although there are many such antigens (agglutinogens), only 2 groups (ABO and rhesus) are commonly used clinically (although others have relevance in the legal profession) ABO blood grouping – This involves 2 antigens; A and B. Individuals who posses the A antigen are said to have type A blood, those with B antigen are type B, those with both antigens are AB, and those with neither antigen are type O. 3 The body of a person carries the antibody (agglutinin) to the antigen they do not posses. Thus if type A blood is given to a type B individual an immune reaction will occur and the blood will coagulate. Since individuals with type AB blood have no antibodies they are ‘universal recipients’ as they can receive any blood group, while type O blood is the ‘universal donor’ as it posses neither antigen. The rhesus blood grouping was first described in rhesus monkeys and relies on the presence of 6 antigens; C, D, E, c, d, e. Only C, D, and E cause immune reactions. If an individual posses any of these antigens they are said to be Rh+, otherwise they are Rh-. Most people are Rh+. The body does not usually contain the antibodies to these antigens, and they take several months to form. The wrong rhesus group can therefore be administered once (thereafter the antibodies are present). Historically people have long looked for a substitute for blood because, before the recognition of different blood groups, transfusions so often failed. Ale, wine, opium and even milk were all used as blood substitutes at one time or another. Recently (1998) solutions of free haemoglobin have been successfully employed. The haemoglobin in such solutions has the ability to carry oxygen but has no antigens. Polymer coatings for rbcs have also been used to neutralise the antigens White Blood cells (Leukocytes) There are 5 types of white blood cell divided into granulocytes (basophils, eosinophils and neutrophils) and agranulocytes (lymphocytes and monocytes). The former have lobed nuclei and granules in their cytoplasm, while the latter have more regular nuclei and no granules. In contrast to red blood cells, leukocytes are generally larger, and much less numerous (7000 mm-3 of blood). White blood cells are the major form of defence against ‘attack’ by potentially harmful foreign organisms such as bacteria, viruses, parasites, fungi etc.. The granulocytes and monocytes, protect the body by phagocytosis , while lymphocytes are involved in the immune response. Neutrophils have a granular cytoplasm and account for 60-70% of all leukocytes. They have a diameter of 10-15 µm and a nucleus composed of 2-5 sausage-shaped lobes. They are powerful phagocytes. Like all leucocytes, neutrophils often leave the vascular system by the process of diapedesis. Before this cells adhere to capillary walls. This is known as margination 4 Prior to phagocytosis objects have to be recognised as foreign. This is done by; roughness, differences in charge, and the presence of antibodies acting as ‘flags’ When a white blood cell encounters a ‘foreign’ object it grows pseudopodia, enclosing the object in a phagocytic vesicle. Proteolytic enzymes released by lysozymes then destroy the object. (Hydrogen peroxide also results in the production of chlorine.) Eventually the neutrophil itself is destroyed and in turn phagocytosed by monocytes. Monocytes are agranular and mature into large macrophages (80 mm) only within the extravascular tissue where they form what is sometimes referred to as the Tissue Macrophage System. They are very powerful phagocytes. Basophils have a diameter of ca 10-15 µm and account for 0.5-2% of all leukocytes. Their nucleus is often Sshaped and their cytoplasm contains large granules. They are weak phagocytes that contain histamine, heparin, serotonin, and are therefore important in the inflammatory response & allergic reactions. They may mature into mast cells Eosinophils are granulocytes and make up 1-4% of all white blood cells. They are 9 µm in diameter and have a bilobed nucleus. Their function is to detoxify foreign proteins and they have a possible role in blood clotting and phagocytosis of the antibody-antigen complex. Lymphocytes develop from their own stem cell. T-lymphocytes mature in the thymus, B-lymphocytes mature in the bone marrow (Bursa of Fabricius in birds). T-lymphocytes mediate cellular immunity in which the whole cell ‘attacks’ the invader. Blymphocytes mediate humoural immunity via plasma cells producing antibodies. You will hear much more about these cells in your lectures on the immune system 5 Blood Platelets (thrombocytes) These are very small (2 µm diam), anucleate cell fragments with a density of 250,00 400,000 mm-3 blood. The have an average life span of 5-14 days. As other blood cell types, platelets are produced in the bone marrow. A megakaryocyte can be up to 160 mm in diameter and disintegrates to produce around 4000 platelets. Platelets are involved in the prevention of blood loss (Haemostasis), which has 3 phases. 1. Vascular phase (endothelial cells produce chemicals which cause;) - vascular spasm lasting ca. 30 mins to close down vessels - division of endothelial cells, smooth muscles etc. to repair wound - endothelial cells to become ‘sticky’ 2. Platelet phase - platelets adhere to the damaged endothelium and aggregate to form a platelet plug. (If the damage is not too severe this is enough to repair the ‘wound’) 3. Coagulation - this occurs via both an extrinsic route (chemicals released by endothelial cells) and an intrinsic pathway (signals initiated by the blood itself) Both intrinsic and extrinsic pathways involve enzyme cascades that ultimately result in the production of substance X and prothrombin activator. This converts a plasma protein (prothrombin) into thrombin, which converts fibrinogen into fibrin threads. Fibrin threads stabilise and form a net that makes up the eventual clot. Depending on the pathway, clot formation occurs in 15 secs - 18 mins. On average it takes 36 mins The final phase of haemostasis is clot retraction, and eventual wound healing 6