Components of Blood The main components of the blood can be split into two parts, the formed elements and plasma. The formed elements make up about 45% of the total volume of the blood, it consists almost entirely of red blood cells, erythrocytes, with various different white cells, or leucocytes and tiny cell fragments called platelets. These last two components make up less than 1% of the total blood volume. The leucocytes are divided into two main groups called granulocytes and agranulocytes. Granulocytes: have irregular lobes nuclei and cytoplasm with prominent granules. The granulocytes consist of the following cells; neutrophils, eosinophils, basophils. Agranulocytes have a smooth round or bean shaped nucleus and no obvious granules in their cytoplasm. They include lymphocytes and monocytes. Functions of blood plasma 1. Transport of materials Water forms 90% of blood plasma and carries many dissolved substances including glucose, amino acids and vitamins. Some substances such as iron and hormones are transported by carrier proteins. Iron ions are carried by the protein tranferrin, this prevents the ion reacting with other substances in the blood. Oxygen is found in the plasma, as it is transferred to the tissues, but it is not the main transport vehicle. Carbon dioxide is transported in the plasma as hydrogen carbonate ions. In addition the water in plasma allows large protein molecules to form a colloidal solution. Lastly the high specific heat capacity of water means that the plasma can act as a heat transferral mechanism with in the body. 2. Regulation of tissue fluid The concentration of dissolved substances in the plasma is higher than in surrounding tissues. As a result water returns to the blood from the tissues fluid. This process depends on the difference in osmotic concentration between the two fluids, the concentration of the blood plasma must be regulated to ensure the correct movement of water. Plasma proteins play an important role in this. Albumens are the most important protein within plasma, they maintain the osmotic levels within limits. If their concentration falls then fluid will not return to the blood and tissues will swell with accumulated fluid, called oedema. 3. Regulation of pH The concentration of H+ ions affects many reactions in the body, and affects the activity and shape of protein molecules. Consequently pH is one of the most important factors that affect homeostasis. The normal pH of the blood plasma and tissue fluid is 7.4, the pH varies by less than 0.04 from this in a normal healthy person. H+ ions are formed mainly by aerobic respiration, this generates carbon dioxide which dissolves in the body fluids, forming carbonic acid, which dissociates to yield H+ ions. Within the plasma, sodium hydrogen carbonate, protein and phosphate (H2PO4) act as pH buffers, temporarily taking up excess H+ ions, H+ ions can be excreted by the kidney. Red blood cells Development - Red blood cell production is restricted to the red bone marrow in the adult human. As an embryo red blood cells are made in the liver and spleen. This red bone marrow is restricted in adults to the vertebral column, rib bones and the ends of the long bones in the arms and legs. The manufacture of red blood cells, called erythropoiesis, takes 5-9 days, the mature red blood cell or erythrocyte is a biconcave disc 8.5 mm in diameter and has no nucleus. Each erythrocyte contains about 280 million haemoglobin molecules. The rate of production is controlled by the hormone erythropoietin released from the kidneys. A decrease in the amount of oxygen reaching the kidneys results in the release of the hormone. Failure to maintain production of red blood cells leads to anaemia. A lack of iron is a common cause of anaemia. Another form of anaemia, called pernicious anaemia, results from a lack of vitamin B12 in the diet. Transport of oxygen. Over 98% of the oxygen carried in the blood is bound to the protein haemoglobin. This is a protein of four sub-units, two a-chains and two bchains. Each of the sub-units contains a haem group, with and iron atom at its centre. A single atom of iron binds one molecule of oxygen. There are four different kinds of oxyhaemoglobin depending on the number of oxygen molecules bound. The ability of the four types of oxyhaemoglobin to bind or release oxygen is not the same. Oxyhaemoglobin 4 binds and releases oxygen more readily than oxyhaemoglobin 3 and so on. This results in a characteristic binding/ release curve, called and oxygen dissociation curve for haemoglobin. The air in lungs has a concentration of oxygen, given as pO2 , of 13 kPa. This is higher than the pO2 of the blood entering the lungs, typically 5 kPa. Therefore dissolved oxygen diffuses rapidly into the blood from the alveoli. The biconcave shape of the red blood cells gives it a very high surface area: volume ratio, this helps the absorption of oxygen. The pO2 in the tissues is variable in the range 1 - 4 kPa, depending on the oxygen demand. As oxygen is used up, the pO2 falls causing the oxygen in the red blood cells to be released. The steepness of the dissociation curve at low kPa means that a small reduction in pO2 results in a large release of oxygen. The shape of the curve is affected by the pH of the locality. Which pH falls as the levels of CO2 build up, and by changes in temperature, in such away that respiring tissues receive the maximum amount of available oxygen. This relationship is known as the Bohr effect. Transport of CO2 The transport of carbon dioxide is closely linked to the transport of oxygen. Carbon dioxide released from tissues dissolves in the tissue fluid and diffuses into the capillaries, the CO2 forms carbonic acid in the plasma, in the red cells this process is speeded up by the enzyme carbonic anhydrase. This results in large amounts of H+ ions as the carbonic acid immediately dissociates to release H+ ions and hydrogen carbonate ions (HCO3-), most of the HCO3- ions diffuse back into the plasma. This loss of negative ions out of the red blood cell is matched by an inward movement of chloride ions (Cl-). This ensures that there is no overall change in the electrical charges, this is known as the chloride shift. The hydrogen ions within the red cells combine with haemoglobin to form a weak acid, called haemoglobinic acid. This uses up some of the haemoglobin, causing further dissociation of oxyhaemoglobin. This helps to explain the Bohr effect. Destruction of red cells Red blood cells have a life span of 90 - 120 days, this is because they cannot repair or maintain themselves due to the lack of nucleus. This also means that they cannot divide. Old red blood cells are recognised and removed from the blood stream by large cells called macrophages, they are found in the liver spleen and bone marrow and collectively form the reticulo-endothelial system. When haemoglobin is broken down the protein or globin elements of the molecule are converted to amino acids which can be reused. The iron atoms are removed from each of the haem groups and pass into the blood plasma where they combine with transferrin for transport to the liver, once there the iron is stored using a second carrier protein called ferritin. The remainder of the haem group is converted to the pigment bilirubin, it is this which is responsible for the yellowish colour of blood plasma. Other oxygen carrying pigments A second oxygen carrying pigment is found in human, called myoglobin. It is found only in muscles. It consists of a single subunit, rather than the four in haemoglobin. Oxygen binds to myoglobin much more tightly than to haemoglobin, it only gives up its oxygen during strenuous activity, when insufficient oxygen is available from the blood. Complete release of myoglobin oxygen occurs when the pO2 of the muscle is close to zero. Another situation which calls for a different pigment occurs during pregnancy, when oxygen must be transferred across the placenta. Fetal haemoglobin has a structure containing a different set of subunits called g-chains. A molecule of fetal haemoglobin therefore contains two a-chains and two g-chains. This alteration shifts the dissociation curve to the left of haemoglobin, as in myoglobin. This means that fetal haemoglobin binds oxygen more tightly than adult haemoglobin and oxygen can be transferred. After birth large numbers of red blood cells are destroyed and replaced by adult haemoglobin, this can sometimes lead to temporary jaundice due to accumulation of bilirubin in the blood. Prevention of blood loss The prevention of blood loss, called haemostasis, is essential for normal functioning of the body. Without it a person would die in a few days due to the accumulation of tiny internal ruptures that occur all the time in the smaller blood vessels. There are five main steps in haemostasis, the first three act to control and seal small ruptures in seconds, large breaches are dealt with by blood clotting. 1. Vessel constriction When any muscular vessel is damaged there is an immediate constriction which restricts blood flow and therefore blood loss. In small arterioles this can block the vessel completely. 2. Sticking of endothelia The cells of the endothelium are altered by the initial injury so that they stick to each other when constricted. They help to maintain the seal as the initial constriction subside. 3. Formation of a platelet plug Platelets are small non-cellular fragments 2-4 mm in diameter, they do not stick to the smooth endothelial lining, but if the cells are damaged it exposes the collagen of the connective tissue underneath, the platelets bind to this forming a mass, or plug. The platelets release chemicals which encourage more platelets to stick together and promote further vasoconstriction. 4. Blood clotting A clot is formed when the soluble protein fibrinogen is converted to the insoluble fibrin. The fibrin forms a mesh which traps the red and white blood cells, converting the free flowing blood into a semi-solid gel. The formation of fibrin is catalysed by the enzyme thrombin. This enzyme is not normally present but is formed from a sequence of reactions known as the coagulation cascade. This 'cascade' involves protein clotting factors. At each step, the inactive form of an enzyme is converted to an active form, which catalyses the next stage of the cascade. Some of the enzymes require Ca2+ ions as co-factors. Vitamin K is not required as a cofactor but needed in the manufacture of prothrombin and other clotting factors. 5. Clot retraction The platelets produce cytoplasmic strands which grow out and stick to the fibrin strands, the strands then contract pulling the clot together, making a denser, stronger clot. Fibrin is eventually broken down by the enzyme plasmin. Plasmin is produced from its inactive form plasminogen when clotting first occurs. It acts slowly to dissolve the clot. Haemophilia is a disease in which the blood fails to clot. Thrombosis occurs when the blood clots excessively. It is serious if the clot affect the blood supply to the heart or brain.