Constituents of Blood
The primary function of blood is to deliver O2 and energy sources to the tissues, and to remove CO2 and waste products. It contains elements of the defence and immune systems, is important for regulation of temperature and transports hormones and other signalling molecules between tissues. In a 70-kg man blood volume is ∼5500 mL, or 8% of body weight. Blood consists of plasma and blood cells. If blood is centrifuged, the cells sediment as the packed cell volume (PCV, haematocrit), normally ∼45% of total volume (i.e. PCV = 0.45) in men, less in women (Figure 5).
The plasma volume is ∼5% of body weight. It consists of ions in solution and a variety of plasma proteins. Normal ranges for key constituents are shown in Figure 5. After clotting, a straw-col- oured fluid called serum remains, from which fibrinogen and other clotting factors have been removed. The relative osmotic pressures of plasma, interstitial and intracellular fluid are critical for maintenance of tissue cell volume, and are related to the amount of osmotically active particles (molecules) per litre, or osmolarity (mosmol/L); as plasma is not an ideal fluid (it contains slow diffusing proteins), the term osmolality (mosmol/kg H2O) is often used instead. Plasma osmolality is ∼290 mosmol/kg H2O, mostly due to dissolved ions and small diffusible molecules (e.g. glucose and urea). These diffuse easily across capillaries, and the crystal- loid osmotic pressure they exert is therefore the same either side of the capillary wall. Proteins do not easily pass through capillary walls, and are responsible for the oncotic (or colloidal osmotic) pressure of the plasma. This is much smaller than crystalloid osmotic pressure, but is critical for fluid transfer across capillary walls because it differs between plasma and interstitial fluid (see Chapter 21). Oncotic pressure is expressed in terms of pressure, and in plasma is normally ∼25 mmHg. Maintenance of plasma osmolality is vital for regulation of blood volume (see Chapter 29).
Na+ is the most prevalent ion in plasma, and the main determinant of plasma osmolality. The figure shows concentrations of the major ions; others are present in smaller amounts. Changes in ionic concentration can have major consequences for excitable tissues (e.g. K+, Ca2+). Whereas Na+, K+ and Cl− completely dissociate in plasma, Ca2+ and Mg2+ are partly bound to plasma proteins, so that free concentration is ∼50% of the total.
Normal total plasma protein concentration is 65–83 g/L. Most plasma proteins other than γ-globulins (see below) are synthesized in the liver. Proteins can ionize as either acids or bases because they have 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, and account for ∼15% of the buffering capacity of blood. Plasma proteins have important transport functions. They bind with many hormones (e.g. cortisol, thyroxine), metals (e.g. iron) and drugs, and therefore modulate their free concentration and thus biological activity. Plasma proteins encompass albumin, fibrinogen and globulins (Figure 5). Globulins are further classified as α-, β- and γ-globulins. β-Globulins include transferrin (iron transport), components of complement (immune system), and prothrombin and plasminogen, which with fibrinogen are involved in blood clotting (Chapter 7). The most important γ-globulins are the immunoglobulins (e.g. IgG, IgE, IgM).
In the adult, all blood cells are produced in the red bone marrow, although in the fetus, and following bone marrow damage in the adult, they are also produced in the liver and spleen. The marrow contains a small number of uncommitted stem cells, which differentiate into specific committed stem cells for each blood cell type.
Platelets are not true cells, but small (∼3 μm) vesicle-like structures formed from megakaryocytes in the bone marrow, containing clearly visible dense granules. Platelets play a key role in haemostasis (Chapter 7), and have a lifespan of ∼4 days.
Erythrocytes (red cells) are by far the most numerous cells in the blood (Figure 5), with ∼5.5 × 1012/L in males (red cell count, RCC). Erythrocytes are biconcave discs with no nucleus, and a mean cell volume (MCV) of ∼85 fL. Each contains ∼30 pg haemoglobin (mean cell haemoglobin, MCH), which is responsible for carriage of O2 and plays an important part in acid–base buffering. Blood contains ∼160 g/L (male) and ∼140 g/L (female) haemoglobin. The shape and flexibility of erythrocytes allows them to deform easily and pass through the capillaries. When blood is allowed to stand in the presence of anticoagulant, the cells slowly sediment (erythrocyte sedimentation rate, ESR). The ESR is increased when cells stack together (form rouleaux), and in pregnancy and inflammatory disease, and decreased by low plasma fibrinogen. Erythrocytes have an average lifespan of 120 days. Their formation (erythropoiesis) and related diseases are discussed in Chapter 6.
Leucocytes (white cells) and platelets
Leucocytes defend the body against infection by foreign material. The normal white blood cell count (WBCC, see Figure 5) increases greatly in disease (leucocytosis). In the newborn infant the WBCC is ∼20 × 109/L. Three main types are present in blood: granulocytes (polymorphonuclear leucocytes, PMN), lymphocytes and monocytes. Granulocytes are further classified as neutrophils (containing neutral-staining granules), eosinophils (acid-staining granules) and basophils (basic-staining granules). All contribute to inflammation by releasing mediators (cytokines) when activated.
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. They are a major constituent of pus. They have a half-life of ∼6 h in blood, days in tissue. Eosinophils are less motile and longer lived, and phagocytose larger parasites. They increase in allergic reactions, and contribute to allergic disease (e.g. asthma) by release of pro-inflammatory cytokines. Basophils release histamine and heparin as part of the inflammatory response, and are similar to tissue mast cells. Lymphocytes originate in the 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 immunoglobulins (antibodies), T cells which coordinate the immune response, and natural killer (NK) cells which kill infected or cancerous cells.
Monocytes are phagocytes with a clear cytoplasm and are larger and longer lived than granulocytes. After formation in the marrow they circulate in the blood for ∼72 h before entering the 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.