Week 9A Ch 16 Neutrophil Function and WBC's PDF

Chapter 16 Benign White Blood Cell Disorders Copyright © 2021 F.A. Davis Company  Learning Objectives  16-1. Characterize the changes in neutrophil count and morphology that develop in response to bacterial infection....

Chapter 16 Benign White Blood Cell Disorders Copyright © 2021 F.A. Davis Company  Learning Objectives  16-1. Characterize the changes in neutrophil count and morphology that develop in response to bacterial infection.  16-2. Define the three modes of neutrophilic migration.  16-3. Describe the changes in migration pattern and appearance that occur in a neutrophil as the result of chemoattractant stimulation.  16-4. Define absolute and relative leukocytosis and leukopenia.  16-5. Appraise the etiology and classic clinical features of Chédiak–Higashi syndrome. Copyright ©2021 F.A. Davis Company  Learning Objectives (cont.)  16-6. List several disorders that present with lymphocytosis.  16-7. Differentiate morphological features of infectious mononucleosis and other reactive lymphocytoses.  16-8. List clinical features of infectious mononucleosis. Copyright ©2021 F.A. Davis Company  Learning Objectives (cont.)  16-12. Evaluate how the Epstein– Barr virus (EBV) affects the B- and T-lymphocyte populations.  16-13. Utilize laboratory results for distinguishing infectious mononucleosis from other lymphocytoses.  16-14. Analyze the molecular basis for the inherited white blood cell disorders. Copyright ©2021 F.A. Davis Company  Neutrophils  Neutrophils are the most numerous leukocytes, accounting for 50% to 70% of all circulating white blood cells (WBCs) in the adult.  They function as phagocytes capable of ameboid movement into the tissues to engulf and destroy bacteria or fungi; they are the first phagocytic cells to mobilize to a site of infection.  They also play a role in mediating inflammatory processes. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.)  Mature neutrophils are smaller than myeloid precursors and thus are more mobile and deformable.  After exiting the proliferative pool of the marrow and entering the bloodstream, mature neutrophils divide equally into marginating and circulating pools, between which there is a constant exchange of cells. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) The marginating pool, not measured by peripheral blood sampling, consists of cells adhering to vessel endothelium within the vascular spaces. Marginating cells enter the tissues by diapedesis in response to inflammation or injury. Neutrophils in the circulating pool leave the blood by random migration after a half-life of ~7 hours and do not return to the bloodstream from tissues. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Little is known of the kinetics of neutrophils after having entered the tissues; they are believed to remain in tissues for several days, where, if not used in an inflammatory process, they die by apoptosis or are destroyed by other phagocytic cells of the reticuloendothelial system or marrow. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.)  Neutrophil function: Phagocytosis occurs in three distinct phases: migration and diapedesis; opsonization and recognition; and ingestion, killing, and digestion. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Neutrophils in the marginating pool roll along vessel endothelium in a random and nondirectional pattern called locomotion, until a site of injury or infection is encountered. ‒ The process of directional migration under the guidance of chemoattractants is known as chemotaxis. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) ‒ Chemoattractants further accelerate the rate of neutrophil migration by a process known as chemokinesis. Ingestion of the opsonized microbe begins as soon as the membrane surface receptor of the neutrophil and microbe bind together. ‒ Membrane pseudopods extend around and envelop the microbe, forming an isolated vacuole within the neutrophil cytoplasm known as a phagosome. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Copyright ©2021 F.A. Davis Company  Neutrophils (cont.)  Neutrophil Margination and Emigration https://www.youtube.com/watch?v=LB9 FYAo7SJU  Neutrophil Chemotaxis https://www.youtube.com/watch?v=ZU UfdP87Ssg  Neutrophil Chasing Bacterium https://www.youtube.com/watch?v=Ep C6G_DGqkI Copyright ©2021 F.A. Davis Company  Neutrophils (cont.)  Disorders of neutrophil function: Neutrophilia, the classic response to infectious and inflammatory processes, is an increase in the absolute or relative number of neutrophils. ‒ The leukemoid reaction is an increase in neutropils in response to inflammation or stress. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) ‒ Leukemoid reaction is characterized by the presence of toxic granulation, Döhle bodies, and cytoplasmic vacuolization in the neutrophils. ‒ Toxic granulation is frequently associated with severe infection in which the cytoplasmic granules enlarge and take on darker staining properties than normal. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Neutropenia is defined as an absolute decrease in the number of circulating neutrophils. ‒ A Quantitative disorder Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) ‒ Most acquired neutropenias occur as transient conditions caused by factors extrinsic to the bone marrow.  Concomitant viral infection, ingestion of certain medications, and alloantibody or autoantibody activity are all reported causes.  Neutropenia may also be acquired as a secondary condition to processes such as aplastic anemia, malignancy of the bone marrow, and dietary B12 or folate deficiency.  Congenital neutropenias occur as chronic or intermittent disorders arising from defective or deficient production is intrinsic to the bone marrow microenvironment; these are extremely rare. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) Qualitative disorders of neutrophil function are characterized by bacterial infections that are caused by hereditary abnormalities in function. ‒ Functional defects of neutrophils, which can be acquired or inherited, are classified by the general type of defect: (1) phagocytic/killing defects, (2) granule function and structure defects, (3) defects affecting chemotaxis and motility, and (4) adhesion defects. Copyright ©2021 F.A. Davis Company  Neutrophils (cont.) ‒ Examination of the peripheral blood smear is necessary for detection but is generally unremarkable in functional defects, with a few notable exceptions: the large granules that characterize Chediak-Higashi syndrome,  Chediak–Higashi syndrome is a rare disorder of neutrophil function characterized by recurrent bacterial infections, partial albinism, and the presence of giant lysosomal granules in nucleated cells. » Management includes prophylactic antimicrobial therapy, and in the case of infection, aggressive intravenous treatment is required. Copyright ©2021 F.A. Davis Company  Eosinophils  Normally, the peripheral blood smear shows ~2% to 4% of eosinophils.  Eosinophils function to release their secondary granules, rich in major basic protein, to destroy parasites and function in immediate hypersensitivity reactions on migration to the tissues. Copyright ©2021 F.A. Davis Company  Eosinophils (cont.)  Causes of eosinophilia can be categorized as neoplastic, reactive, and idiopathic. The most common cause of eosinophilia worldwide is parasitic infections. In developed countries, allergic disorders are the most common causes of reactive eosinophilia. Copyright ©2021 F.A. Davis Company  Basophils  Normally, the peripheral blood smear shows 1% to 2% of basophils. Isolated basophilia is uncommon. Reactive conditions can cause moderately increased basophil counts, and uncommonly occur secondary to allergy, hypersensitivity, or inflammation due to the major component of basophilic granules being histamine. Copyright ©2021 F.A. Davis Company  Basophils (cont.) More commonly, basophilia is indicative of a malignant process and characterized by absolute counts that are much higher due to the extreme elevation in WBC count characteristic of myeloproliferative neoplasms. Chronic myelogenous leukemia (CML) is the most common cause of basophilia. Copyright ©2021 F.A. Davis Company  Monocytes  Normally, the peripheral smear shows 2% to 9% of monocytes.  Monocytes, on migration to the tissues, function in phagocytic and antimicrobial activities, tissue repair, and various other functions.  Monocytes contain numerous very fine granules in their cytoplasm that play a major role in destruction of microbes. Copyright ©2021 F.A. Davis Company  Monocytes (cont.) Functions of the proteins secreted by monocytes include: ‒ Regulation of hematopoiesis ‒ Stimulation of inflammatory reactions ‒ Removal of infectious organisms by phagocytosis ‒ Removal of senescent blood cells ‒ Modulation of the immune function ‒ Stimulation of host defense against tumor cells Copyright ©2021 F.A. Davis Company  Monocytes (cont.) Monocytosis. ‒ Reactive monocytosis is generally associated with a chronic infection, autoimmune disease, splenectomy, and a range of malignancy. ‒ Absolute monocytosis can also be found in malignant hematopoietic disorders such as chronic myelomonocytic leukemia (CMML), chronic myelogenous leukemia (CML), acute monocytic leukemia, and acute myelomonocytic leukemia (AMML). Copyright ©2021 F.A. Davis Company  Lymphocytes  Lymphocytosis is an increase in lymphocytes in the peripheral blood.  In adults, lymphocytes represent 20% to 40% of the relative differential count. Relative lymphocytosis refers to an increase in the percentage of lymphocytes when performing the WBC differential. Absolute lymphocytosis represents the total number of lymphocytes present and is calculated as a relative percentage of the overall WBC count. Copyright ©2021 F.A. Davis Company  Lymphocytes (cont.)  Absolute lymphocytosis: reactive vs. malignant causes: Reactive lymphocytes describe transformed or benign lymphocytes; the term atypical should not be used interchangeably with reactive because, in pathology, atypical may imply malignant-appearing cells. Copyright ©2021 F.A. Davis Company  Lymphocytes (cont.) Reactive lymphocytes and normal lymphocytes vary in size, shape, and immunophenotypic markers (polyclonal). Malignant lymphocytes may vary in size depending on the particular malignancy. Copyright ©2021 F.A. Davis Company  Lymphocytes (cont.) TABLE 16-7 Lymphocyte Morphologies Characteristic Reactive Resting Small s Lymphocyte Lymphocyte* Size Large (9–30 Small (8–12 mm) mm) N:C Ratio† Low to moderate High to moderate Cytoplasm Abundant Scant amount Cytoplasm Color Colorless to dark Colorless to light blue blue Nucleus shape Round to Round irregular Chromatin Coarse to Coarse Copyright ©2021 F.A. Davis moderately fine‡ Company