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4.1 The red blood cell differs from almost all other body cells as it has no nucleus (therefore allowing it easy passage through the smallest capillaries) and no intracellular organelles but contains haemoglobin. The membrane is also ‘weak’ compared to nucleated cells, and this allows deformability and free passage of oxygen.
4.2 Reticulocytes are larger than mature red blood cells and often have a ‘bluish’ tinge when stained conventionally and viewed by light microscopy. Reticulocytes contain a network of stringy RNA remnants (which give the cell its name).
4.3 The major components of the red blood cell membrane are a phospholipid and cholesterol bilayer, an internal cytoskeletal scaffold, and various proteins and glycoproteins embedded within the phospholipid bilayer. The structures of the membrane allow adhesion and recognition, the transport of water, and dissolved gases and ions, permit enzymatic reactions, and also give the red blood cell its characteristic round but flattened shape (biconcave).
4.4 Iron is absorbed from the foodstuffs in the intestine into intestinal cells themselves (enterocytes) via the cell surface protein divalent metal transporter-1. The export of iron into the circulation via ferroportin is controlled by hepcidin, itself a product of the liver.
4.5 Almost all iron is carried in the blood by transferrin. Upon arrival in the bone marrow, the iron-loaded transferrin gains entry to the developing red blood cell precursor (such as the erythroblast) via the transferrin receptor, a component of the cell membrane.
4.6 Vitamins B6 and B12 are essential co-factors for enzymes that synthesize the precursors to the haem molecule. This happens within the mitochondria of developing red blood cell precursors such as the erythroblast.
4.7 The major types of globin proteins found that make up haemoglobin in the adult are alpha, beta, delta and gamma. Two alpha-chains and two gamma-chains make up haemoglobin F, two alpha-chains and two delta-chains make up haemoglobin A2, whilst two alpha-chains and two beta-chains make up haemoglobin A.
4.8 There are several functions of the metabolic pathway within the red cell. These include the provision of energy by anaerobic respiration, the generation of the anti-oxidant amino acid glutathione, and the generation of 2,3-diphosphoglycerate, which influences the release of oxygen from oxyhaemoglobin.
4.9 Oxygen is dangerous to the cell as it can oxidize and so damage the proteins, fats and carbohydrates of the cytoplasm. Collectively, these dangerous types of oxygen may be described as ‘reactive oxygen species’, an example of which is the superoxide anion.
4.10 The left and right shifts govern the degree of uptake and release of oxygen by deoxyhaemoglobin and oxyhaemoglobin respectively at the lungs and tissues respectively. This in turn is influenced by pH, temperature and the concentration of 2,3-DPG.
4.11 Since the red cell cannot synthesize new enzymes, as it gets old its enzymes are used up. Consequently, it cannot maintain its flexibility and resist oxidant damage. These lead to its destruction by cells of the reticular-endothelial system such as macrophages.
4.12 The major excretory product of the red blood cell is bilirubin. It is excreted via the kidney and intestines, possibly conjugated to glucuronic acid.
4.13 The red cell distribution width (RDW) gives an indication of possible abnormalities in the overall size distribution of the red cell population.
4.14 Red cells whose size is below the reference range may be described as microcytes, whilst those whose size exceeds this range are macrocytes. It follows that cells whose size is within the reference range are normocytes.
4.15 Hypochromic translates to ‘low colour’, and generally reflects a reduced amount of haemoglobin in the cell, and therefore a low MCH and MCHC, as may be found in certain types of anaemia.
4.16 The principle difference is that almost all cases of PV are driven by a gain in function mutation in a gene for a component of the Epo receptor, JAK-2. Furthermore, PV is part of a triad of myeloproliferative neoplasms that include myelofibrosis and essential thrombocythaemia, and which may transform to an acute myeloid leukaemia. Unlike PV, the white cell count and platelet count are rarely increase in erythrocytosis, as the aetiology is based on abnormalities in the hypoxia sensing pathways and so high levels of Epo.