The five types of leucocytes found in peripheral blood are neutrophils, eosinophils and basophils (which are all called granulocytes) and lymphocytes and monocytes. The development of these cells is shown.
The earliest morphologically identifiable precursors of neutrophils in the bone marrow are myeloblasts, which are large cells constituting up to 3.5% of the nucleated cells in the marrow. The nucleus is large and contains two to five nucleoli. The cytoplasm is scanty and contains no granules. Promyelocytes are similar to myeloblasts but have some primary cytoplasmic granules containing enzymes such as myeloperoxidase. Myelocytes are smaller cells without nucleoli but with more abundant cytoplasm and both primary and secondary granules. Indentation of the nucleus marks the change from myelocyte to metamyelocyte. The mature neutrophil is a smaller cell with a nucleus with two to five lobes with predominantly secondary granules in the cytoplasm which contain lysozyme, collagenase and lactoferrin.
Peripheral blood neutrophils are equally distributed into a circulating pool and a marginating pool lying along the endothelium of blood vessels. In contrast to the prolonged maturation time of about 10 days for neutrophils in the bone marrow, their half-life in the peripheral blood is extremely short, only 6-8 hours. In response to stimuli (e.g. infection, corticosteroid therapy) neutrophils are released into the circulating pool from both the marginating pool and the marrow. Immature white cells are released from the marrow when a rapid response (within hours) occurs in acute infection (described as a ‘shift to the left’ on a blood film).
The prime function of neutrophils is to ingest and kill bacteria, fungi and damaged cells. Neutrophils are attracted to sites of infection or inflammation by chernotaxins. Recognition of foreign or dead material is aided by coating of particles with immunoglobulin and complement (opsonization) as neutrophils have Fc and C3b receptors . The material is ingested into vacuoles where it is subjected to enzymic destruction, which is either oxygen-dependent with the generation of hydrogen peroxide (myeloperoxidase) or oxygen-independent (lysosomal enzymes and lactoferrin).
A rise in the number of circulating neutrophils to >10 x 109/litre occurs in bacterial infections or as a result of tissue damage. This may also be seen in pregnancy, during exercise and after corticosteroid administration With any tissue necrosis there is a release of various soluble factors, causing a leucocytosis.
Interleukin-l is also released in tissue necrosis and causes a pyrexia. The pyrexia and leucocytosis accompanying a myocardial infarction are a good example of this and may be wrongly attributed to infection.
A leukaemoid reaction (an overproduction of white cells, with many immature cells) may occur in severe infections, tuberculosis, malignant infiltration of the bone marrow and occasionally after haemorrhage or haemoly- SIS.
In leucoerythroblastic anaemia, nucleated red cells and white cell precursors are found in the peripheral blood; causes include marrow infiltration with metastatic carcinoma, myelofibrosis, osteopetrosis, myeloma, lymphoma and occasionally severe haemolytic or megaloblastic anaemia. Neutropenia and agranulocytosis
• eutropenia is defined as a circulatory neutrophil count below 1.5 x 109/litre. A virtual absence of neutrophils is called agranulocytosis. The causes are given.
Infections may be frequent, often serious, and are more likely as the neutrophil count falls. A characteristic glazed mucositis occurs in the mouth and ulceration is common.
The blood film shows marked neutropenia. The appearance of the bone marrow will indicate whether the neutropenia is due to depressed production or increased destruction of neutrophils. Neutrophil antibody studies may be performed if an immune mechanism is suspected.
Antibiotic therapy should be given to patients with acute severe neutropenia as necessary.
If the neutropenia seems likely to have been caused by a drug, all current drug therapy should be stopped. Recovery of the neutrophil count usually occurs after about 10 days. G-CSF is used after chemotherapy.
Steroids and high-dose intravenous immunoglobulin are used to treat patients with severe autoimmune neutropenia and recurrent infections.
Eosinophils are slightly larger than neutrophils and are characterized by a nucleus with usually two lobes and large cytoplasmic granules that stain deeply red. The eosinophil seems to play some part in allergic responses and in the defence against infections with helminths and protozoa.
Eosinophilia is said to occur when the number of eosinophils is >0.4 x 109/litre in the peripheral blood. It is associated with a wide variety of disorders. The causes of eosinophilia are listed.
The nucleus of basophils is similar to neutrophils but the cytoplasm is filled with large black granules. The granules contain histamine, heparin and enzymes such as myeloperoxidase. The physiological role of the basophil is not known. Binding of IgE causes the cells to degranulate and release histamine and other contents involved in acute hypersensitivity reactions.
Basophils are usually few in number «1 X 109/litre) but are significantly increased in myeloproliferative disorders.
Monocytes are slightly larger than neutrophils. The nucleus has a variable shape and may be round, indented or lobulated. The cytoplasm contains less granules than neutrophils. Monocytes are precursors of tissue macrophages and spend only a few hours in the blood but can continue to proliferate in the tissues for many years.
A monocytosis (>0.8 X 109/litre) may be seen in chronic bacterial infections such as tuberculosis or infective endocarditis, chronic neutropenia and patients with myelodysplasia particularly chronic myelomonocytic leukaemia.
Lymphocytes form nearly half the circulating white cells. They descend from pluripotential stem cells. Circulating lymphocytes are small cells, a little larger than red cells, with a dark-staining central nucleus. There are two main types: the thymus-dependent or T lymphocytes, which are concerned with cellular immunity and form about 80% of the circulating lymphocytes, and the ‘bursa dependent’ or B lymphocytes, which are concerned with humoral immunity .
Lymphocytosis (lymphocyte count >5 x 109/litre) occurs in response to viral infections, particularly EBV, CMV and HIV and chronic infections such as tuberculosis and toxoplasmosis. It also occurs in chronic lymphocytic leukaemia and in some lymphomas.