Microbiology 435 Leukocyte Abnormalities

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Common Morphological Abnormalities of Neutrophils Toxic change - a visible response to infection as seen in neutrophils. Toxic change is characterized by: Toxic granules seen in segmented neutrophils, bands (book says monocytes also) enlarged, prominent dark primary granules in the cytoplasm Dohle bodies seen in cytoplasm of neutrophils, light blue inclusions in the cytoplasm, round to oval in shape represent aggregated rough endoplasmic reticulum (RNA) Cytoplasmic vacuolization phagocytic vacuoles in cytoplasm of neutrophil associated with bacteremia Cytoplasmic basophilia dark blue cytoplasm of neutrophils due to retained ribosome (DNA) and rough endoplasmic reticulum indication of impaired cytoplasmic maturation Other morphological abnormalities Hypersegmentation seen in segmented neutrophils nucleus has more than 5 lobes associated with vitamin B12 or folic acid deficiencies a "pseudohypersegmentation" is seen in old segmented neutrophils as part of the dying process. Pyknosis as cells degenerate the nuclei may appear exploded or as solid spheres chromatin has lost all pattern and is all solid looking  may be confused with basophils but nuclear spheres are usually too large to be specific granules. LEUKOCYTE DISORDERS LEUKOCYTOSIS - increased number of leukocytes in peripheral blood. The increase can be caused by an increase in any of the individual leukocytes. Reactive disorders involve a normal physiologic response to an outside injury and are characterized by a WBC count > 10,000/ul. Proliferative disorders involve an abnormal response, for example the leukemias; and are characterized by a WBC count up to 100,000/ul. Leukemoid reaction resembles leukemia but is a severe (WBC> 50,000/ul) reactive disorder. Neutrophilia is the most common cause of a leukocytosis. The neutrophilia may or may not be accompanied by a left shift (increased number of immature neutrophils in peripheral blood). Some of the common causes of neutrophilia are: Acute bacterial infection - especially with pyogenic bacteria causing either a localized infection like appendicitis or a generalized infection like septicemia. Streptococci, Staphylococci and Pneumococci are most often involved. Also commonly involved are gram negative enteric bacteria, and endogenous flora. Most infections occur in tissues e.g. boils, abscesses. Inflammatory conditions like infarction (insufficient blood supply to tissues), a myositis (inflammation of a muscle), vasculitis (inflammation of a vessel or phlebitis, inflammation of a vein) Intoxication : a)Metabolic, for example, uremia seen with kidney failure or b) Chemical/drug induced, for example, lead, mercury; digitalis for treatment of congestive heart failure; turpentine, insect venom; epinephrine and cortisone. Neoplasm - will see an increase in neutrophils associated with fast growing tumors such a carcinoma, lymphoma, melanoma. They outgrow their blood supply and become necrotic. Hemolysis - especially when caused by splenectomy or transfusion reactions. In the case of splenectomy the spleen is no longer there to clean up the debris from the normal breakdown of erythrocytes and neutrophils are "called in" to clean up the blood. In transfusion reactions the erythrocytes are hemolyzed from the mismatched blood types (patient antibodies attack donor cells). Hemorrhage - the mechanism is not entirely understood, but the response is greater when the hemorrhage is internal. Physiological stress - heat, cold, vigorous exercise Neutrophilia happens when There is an increased commitment of stem cells to the neutrophil line The time needed to mature to the myelocytes stage is shortened Extra divisions of myelocytes, produce more neutrophils There is an accelerated overall transit time through bone marrow Eosinophilia Some causes of eosinophilia are active allergic disorders like asthma or hay fever tissue parasite infection dermatoses like eczema and hives certain drugs Basophilia Some causes of basophilia are: hyperlipidemia small pox and chickenpox chronic sinusitis ulcerative colitis chronic myelogenous leukemia polycythemia vera Monocytosis is seen whenever there is increased cell damage: in the recovery phase of acute infection increased cell damage like from tissue trauma, bacterial endocarditis, TB collagen disorders such as rheumatoid arthritis, systemic lupus erythematosus or liver cirrhosis post splenectomy - monocytes are busy cleaning up like neutrophils inflammatory bowel disease Lymphocytosis Common causes of lymphocytosis are: viral disorders - e.g. will see variant lymphocytes with mononucleosis and cytomegalovirus, influenza, infectious lymphocytosis, bacterial disorders - e.g. Whooping cough (Bordetella pertussis), TB parasitic disorders - e.g. Toxoplasma gondii (a tissue coccidia) drug reactions - certain anticonvulsants   LEUKOCYTOPENIA - a decrease in the number of circulating leukocytes. Because the neutrophil is the most common leukocyte in peripheral blood, neutropenia is the most common cause of leukocytopenia. Neutropenia can be caused by depletion of neutrophils in response to recurrent, chronic or overwhelming infection or inflammation (body tries to compensate by increasing monocyte and humoral and cell-mediated activities) entrapment of neutrophils in the spleen, in a disease problem of hematopoiesis nutritional deficiencies; e.g. vitamin B12 (pernicious anemia) or folate deficiency acquired disorders, e.g. drugs, chemicals, radiation in some children with viral infections neutrophils may actually decrease Some causes of eosinopenia are: any stressful condition resulting in release of adrenal corticoids or epinephrine as an aftermath of acute inflammation Basopenia is difficult to quantify because they are so rarely seen in peripheral blood. However, basopenia can be associated with: patients with hyperthyroidism may have decreased basophils acute stress Monocytopenia has been identified with Hairy Cell Leukemia prednisone therapy Lymphocytopenia is seen as a common response to stress and to corticosteroids with immune deficiency disorders - e.g. AIDS, systemic lupus erythematosus after exposure to physical agents - e.g. radiation following administration of cytotoxic drugs in cases of infectious hepatitis   PROLIFERATIVE DISORDERS - a spontaneous abnormal multiplication of cells Leukemia - neoplastic proliferative disease predominantly involving leukocytes resulting in an overproduction of various types of immature or mature leukocytes in the bone marrow and/or peripheral blood. This occurs when one or more normal hematopoietic progenitor cells is malignantly transformed resulting in proliferation of malignant offspring. Forms of leukemia acute short duration many immature cells in bone marrow and/or peripheral blood elevated total WBC count prognosis from several weeks to several months, if left untreated, from the time of diagnosis. chronic long duration mostly mature cells extremely elevated to lower than normal prognosis from months to many years Classification of leukemias Myelogenous (acute and chronic) Monocytic (acute and chronic) Lymphocytic (acute and chronic) Other uncommon forms Factors relating to the occurrence of leukemias Probably the transformation has been caused by mutation and altered expression of specific genes. Known factors associated with leukemias (and lymphomas) oncogenes - transforming genes in retroviruses, associated with acute leukemias radiation chemicals genetic factors infectious agents - Epstein Barr, HIV   Lymphomas are solid, malignant tumors of the lymph nodes and associated lymphoid tissues. The lymphocyte is the cell involved. The malignant cells are initially confined to the organs containing mononuclear phagocyte cells such as the lymph nodes, spleen, liver, and bone marrow. They can spill over into the circulating blood and look like leukemia. Major forms Hodgkin’s lymphoma non-Hodgkin’s lymphoma