Blood consists of:
• Red cells
• White cells
• Plasma, in which the above elements are suspended Plasma is the liquid component of blood, which contains soluble fibrinogen. Serum is what remains after the formation of the fibrin clot.
The formation of blood cells (haemopoiesis)
Around the third week of development of the embryo, blood islands are formed in the yolk sac and produce primitive blood cells which migrate to the liver and spleen. These organs are the chief sites of haemopoiesis from 6 weeks to 6-7 months of fetal life. The bone marrow becomes the main source of blood cells for the remainder of fetal life and is the only source of blood cells during normal childhood and adult life.At birth, haemopoiesis occurs in the marrow of nearly every bone. As the child grows the marrow cavity starts to be replaced by fat so that haemopoiesis in the adult becomes confined to the central skeleton and the proximal ends of the long bones. Only if the demand for blood cells increases and persists do the areas of red marrow extend once again. Pathological processes interfering with normal haemopoiesis may result in resumption of haemopoietic activity in the liver and spleen, which isreferred to as extramedullary haemopoiesis.
All peripheral blood cells are derived from pluripotential stem cells by a number of differentiation steps. Stem cells probably resemble small lymphocytes, although their exact appearance remains unknown.
However, their presence can be shown by bone marrow culture techniques, involving the detection of colony-forming units (CFUs) in agar culture medium. The earliest detectable CFU is CFU-S (spleen); this gives rise to CFUGEMM, which produces CFU ‘committed’ to the production of:
• Erythroid cells
Stem cells also produce lymphoid cells.
Stem cells have the capability for self-renewal, as well as differentiation, and maintain a constant cellularity in a normal healthy marrow.
Haemopoietic growth factors
Haemopoietic growth factors are glycoproteins which regulate the differentiation and proliferation of haemopoietic progenitor cells and the function of mature blood cells. They act on receptors expressed on haemopoietic cells at various stages of development to maintain the haemopoietic progenitor cells and to stimulate increased production of one or more cell lines in response to stresses such as blood loss and infection. More than one growth factor is often needed to stimulate a particular cell to differentiate or proliferate.
Haemopoietic growth factors include erythropoietin, colony-stimulating factors (CSFs, the prefix indicating the cell type, see Fig. 6.1) and interleukins (IL). T lymphocytes, monocytes and bone marrow stromal cells such as fibroblasts, endothelial cells and macrophages are the major sources except for erythropoietin, which is mainly produced in the kidney. Many growth factors have been produced by recombinant DNA techniques and are being used clinically. Examples include G-CSF which is used to accelerate haemopoietic recovery after chemotherapy and bone marrow transplantation, and erythropoietin which is used to treat anaemia in patients with chronic renal failure.
Peripheral blood-normal values
Automated cell counters are used to measure the level of haemoglobin (Hb) and the number and size of red cells, white cells and platelets. Other indices can be derived from these values. The mean corpuscular volume (MCV) of red cells is the most useful of the indices and is used to classify anaemia.
The white cell count (WCC) gives the total number of circulating leucocytes and many automated cell counters produce differential counts as well.Normally less than 2% of the red cells are reticulocytes . The reticulocyte count gives a guide to the erythroid activity in the bone marrow. An increased ount is seen with haemorrhage or haemolysis, or after the response to treatment with a specific haematinic. A low count in the presence of anaemia indicates an inappropriate response by the bone marrow and may be seen in bone marrow failure (from whatever cause) or where there is a deficiency of a haematinic.
A carefully evaluated blood film is still an essential adjunct to the above, as definitive abnormalities of cells can be seen.
ERYTHROCYTE SEDIMENTATION RATE (ESR). This is the rate of fall of red cells in a column of blood and is a measure of the acute phase response. The pathological process may be immunological, infective, ischaemic, malignant or traumatic. A raised ESR reflects an increase in the plasma concentration of large proteins, such as fibrinogen and immunoglobulins. The proteins cause rouleaux formation, when cells clump together like a stack of coins, and therefore fall more rapidly. The ESR increases with age, and is higher in females than males. It is low in polycythaernia vera due to the high red cell concentration and increased in patients with severe anaemia.
PLASMA VISCOSITY measurement is being used instead of the ESR in many laboratories. As with the ESR, the level is dependent on the concentration oflarge molecules such as fibrinogen and immunoglobulins. There is no difference between levels found in males and females and viscosity only increases slightly in the elderly. It is not affected by the level of Hb and the result may be obtained within 15 min.
C-REACTIVE PROTEIN is one of the proteins produced in the acute phase response. It is synthesized exclusively in the liver and rises within 6 hours of an acute event. It rises with temperature (possibly triggered by IL-I) and in inflammatory conditions and after trauma. It follows the clinical state of the patient much more rapidly than the ESR and is unaffected by the level of Hb. Its measurement is easy and quick to perform using an immunoassay that can be automated. It is being increasingly used instead of the ESR, although more sophisticated equipment is required and it is more expensive, particularly when assayed in small numbers.