The primary function of blood is to deliver O2 and energy to the tissues, and remove CO2 and waste products. It is also important for the defence and immune systems, regulation of temperature, and trans- port of hormones and signalling molecules between tissues. Blood consists of plasma (Chapter 2) and blood cells. Red blood cells contain haemoglobin and transport respiratory gases (Chapter 28), whereas white cells form part of the defence system (Chapter 10). In adults, all blood cells are produced in the red bone marrow. Normal values for cell counts, haemoglobin and proportion of blood volume due to red cells (haematocrit or packed cell volume; estimated by centrifuging a blood sample) are shown in Figure 8a. Platelets are discussed in Chapter 9.
Plasma contains several important proteins (Fig. 8b), with a total concentration of 65–83 g/L. Most, other than γ-globulins (see below), are synthesized in the liver. Proteins can ionize as either acids or bases because of the presence of both NH2 and COOH groups. At pH 7.4 they are mostly in the anionic (acidic) form. Their ability to accept or donate H+ means they can act as buffers (Chapter 36). Plasma proteins have important transport functions, as they bind many hormones (e.g. cortisol and thyroxine) and metals (e.g. iron). They are classified into albumin, globulin and fibrinogen fractions. Globulins are further classified as α-, β- and γ-globulins. Examples and their major functions are shown in Figure 8b.
Red blood cells
Red blood cells (erythrocytes) are biconcave discs ∼8 μm wide, and uniquely have no nucleus. They therefore cannot repair themselves and have a lifespan of only 100–120 days. The shape and flexibility of red cells allows them to deform easily and pass through capillaries. Importantly, they contain haemoglobin which is responsible for carriage of O2, and also plays a role in acid–base buffering (Chapter 28 and 36).
Red cells are formed by a process called erythropoiesis (Fig. 8c). They originate from committed stem cells in the bone marrow of the adult, and liver and spleen of the fetus. The glycoprotein hormone erythropoietin (EPO) increases the number of committed stem cells and promotes production of red cells. Erythropoietin is produced mainly by the kidneys in adults, and liver in the fetus. The key stimulus for increased erythropoietin is low O2 (hypoxia). Stem cells differenti- ate into erythroblasts (early normoblasts), which are relatively large (∼15 μm) and nucleated. As differentiation proceeds, the cells shrink and haemoglobin is synthesized, which requires iron, folate and vitamin B12. In the late normoblast the nucleus breaks up and disappears. The young red cell shows a reticulum on staining, and is called a reticulocyte. As it ages, the reticulum disappears and the character- istic biconcave shape develops. Normally 1–2% of circulating red cells are reticulocytes. This increases when erythropoiesis is enhanced (e.g. by hypoxia). About 2 × 1011 red cells are produced from the marrow each day. The spleen holds a reserve of red cells that can be released following blood loss.
Red cells are destroyed by macrophages in the liver and spleen after ∼120 days. The haem group is split from haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled via transferrin, an iron transport protein, or stored in ferritin. Bilirubin is a brown–yellow compound which is excreted in the bile. An increased rate of haemoglobin breakdown results in excess bilirubin, which stains the tissues (jaundice).
An inadequate amount of red cells and/or haemoglobin is called anaemia. This is commonly a result of haemorrhage (e.g. heavy menstruation), but also occurs when the diet contains insufficient iron, folate or vitamin B12, or they are poorly absorbed in the gut (Chapter 39). Anaemia is also caused by abnormalities of haemoglobin (thalassaemia), the sickle cell mutation and leukaemia (white cell cancers).
Red cells have surface antigens that can react with specific antibodies in the plasma. The antigens and antibodies present are determined genetically, forming the basis of blood groups. The most important systems are ABO (A, B, both or neither antigens present) and Rh (Rhesus; D or no D antigen). Matching of blood groups is essential during blood transfusions, because red cells with a different antigen to the recipient will react with antibodies in the plasma, stick together (agglutinate) and haemolyse (break apart). The Rh system is important in pregnancy, because an Rh– mother can be sensitized (produce antibodies) to red cells from a Rh+ fetus during birth. This can be a problem for a second pregnancy with another Rh+ fetus, as antibodies cross the placenta.
White blood cells
White blood cells (leucocytes) defend the body against infection by foreign material, and the white cell count (Fig. 8a) increases greatly in disease. Three main types are present in blood: granulocytes, lym- phocytes and monocytes.
Granulocytes are further classified as neutrophils (neutral-staining granules), eosinophils (acid-staining granules) and basophils (basic-staining granules) (Fig. 8d). All contribute to inflammation by releas- ing mediators. Neutrophils have a key role in the innate immune system, and migrate to areas of infection (chemotaxis) within minutes, where they destroy bacteria by phagocytosis (engulfing them). They are a major component of pus. Neutrophils live for ∼6 h in blood, longer in tissues. Eosinophils are less motile but longer lived, and phagocytose larger parasites. They are increased in allergic disease, to which they contribute by releasing inflammatory mediators. Basophils release histamine and heparin as part of the inflammatory response and are similar to tissue mast cells.
Lymphocytes originate in the bone marrow but mature in the lymph nodes, thymus and spleen before returning to the circulation. Most remain in the lymphatic system. Lymphocytes are critical components of the immune system and are of three main forms: B cells which produce γ-globulins (immunoglobulins, antibodies), T cells which coordinate the immune response, and natural killer (NK) cells which kill infected or cancerous cells (Chapter 10).
Monocytes are phagocytes but larger and longer lived than granulocytes. After formation in the marrow they circulate in the blood for ∼72 h before entering tissues to become macrophages, which unlike granulocytes can also dispose of dead cell debris. Macrophages form the reticuloendothelial system in liver, spleen and lymph nodes.