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Chapter 8 WBC.Pdf Morphologic and Distributive Leukocyte Disorders Leucocytes differentiation Only Mature WBC cells should present in peripheral Blood Normal WBC count The formation of Neutrophil, Monocyte, Macrophage Life span of neutrophil in Blood is 6-10 hours Granules in Neutrophils: Primary granules: promyelocyte stage Secondary granules: myelocyte stage and predominate therafter Granulopoiesis Neutrophil kinetics Distribution of Macrophages Phagocytosis and bacterial destruction 1. Bacteria enter the neutrophil surrounded by invaginated cell membrane 2. Fusion with primary lysosome to form phagosome. 3. Enzymes including lactoferrin attack the organism Undigested bacteria remains excreted by exocytosis Abnormal WBC Toxic granules Dohle bodies Hypersegmented Basophilic inclusions Peter heut anomaly Bizzare giant granules Alders anomalies Quantitative WBC Disorders Introduction • Leukocytes function to protect the body against foreign organisms or antigens. • In doing so, they undergo visible changes that can be detected and evaluated macro- and microscopically. • The changes fall into two categories: 1. Quantitative or macro changes alterations in numbers of cells . Absolute . Relative 2. Qualitative or micro changes alterations in cell morphology . Nucleus . Cytoplasm Definitions White Cell Numbers Leukocytosis: increase in the numbers of circulating white cells >12,000/uL Leukopenia: decrease in the numbers of circulating white cells < 4,000/uL Left Shift – increased circulating numbers of immature neutrophils Leukoerythroblastic Reaction – leukocytosis with a left shift accompanied by nucleated red cells: seen in malignancy. Leukemoid Reaction – benign excessive leukocytosis accompanied by an exaggerated neutrophilia and a left shift in response to an infection; the WBC > 50 x 109/L http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20leuko%20Eblastic%20x50.jpeg Neutrophilia >7.5 x 109/L Other defining features: 1. Left shift – Increased band forms 2. “toxic” cell appearance • Dohle bodies • Vacuoles • Intra-cellular microbes Causes of Neutrophilia • Infections • Other o (primarily bacterial) o autoimmune disorders • Drugs/Hormones o stress o severe physical activity o epinephrine o pregnancy o corticosteroids o smoking o lithium o acute hemorrhage o venoms/poisons/toxins o post-splenectomy • Tissue necrosis o myeloproliferative disorders o acute gout • Metabolic o burns o ketoacidosis o trauma o uremia o infarcts o eclampsia o thyrotoxicosis Graphic accessed URL http://www.med-ed.virginia.edu/courses/path/innes/wcd/leukocytosis.cfm, 2010. Pathophysiology Demargination of • Stress marginated pool of cells (pseudoneutrophilia) . doubling of count Release of BM-storage Acute Inflammation pools left shift Increased cell production • Chronic Infection sustained neutrophilia Eosinophilia Absolute count >0.5 x 109/L Causes: parasites Helminths drug treatments allergies infections neoplasms Chronic myeloid leukemia (CML) autoimmune disorders Basophilia 9 Absolute count >0.15 x 10 /L Causes: CML allergies inflammatory disorders irradiation viral infections Monocytosis Absolute count >0.8 x 109/L Most commonly seen in conditions with increased cell damage - Chronic infection [TB, syphilis, protozoal infections, rickettsial infections] Recovery from agranulocytosis Post-splenectomy Strenuous exercise Subacute bacterial endocarditis Neutropenia < 2.5 x 109/L • Definition: less than the normal Causes absolute count; greatly influenced • Reactions to Drugs by patient age and race. – BM ablative therapy – African and Middle Eastern populations • Infections • Subclasses include mild, moderate – HIV/Hepatitis and severe – Typhoid/ miliary TB – Malaria • Immune Disorders – Systemic lupus erythromatous (SLE) • Neoplasm • BM Failure – Megaloblastic Anemia – Aplastic Anemia • Hypersplenism • Idiopathic (of unknown cause). Neutropenia Pathophysiology Defects inside or outside the Bone Marrow Decreased proliferation [failure of cells - aplasia] Decreased maturation [insufficient number of precursors undergoing abnormal maturation] Decreased survival [increased destruction and/or rapid removal of cells] Distribution [total body pools are normal, circulating numbers are reduced] Lymphocytosis Absolute count >5.5 x 109/L Normally: • Causes 60-80% circulating – Infections • Viral lymphs are T-cells – Infectious mononucleosis [2:1 CD4/CD8] • Bacterial – Pertussis 10-20% are B-lymphs – Thyrotoxicosis 5-10% are natural – Recovery from acute killer or NK cells infections – Neoplasm • Leukemias • Lymphomas Infectious Mononucleosis • Acute, self-limiting, febrile infection of B-cells • Circulating reactive lymphocytes are primary CD8 T-cells • Typically occurs in those age 10-25 years Fever Sore throat Lymphadenopathy Lethargy Positive serology – Heterophile antibodies Graphic accessed URL http://www.md.huji.ac.il/mirror/webpath/HEME013.jpg, 2005. Lymphopenia Absolute lymphocyte count <0.6 x 109/L • There are three types of abnormalities: Decreased production Increased destruction Changes in distribution Lymphopenia – Decreased production – Redistribution SCID = severe Glucocorticoid combined therapy immunodeficiency Anesthesia Protein-calorie malnutrition TB Zinc deficiency Influenza – Increased destruction Burns HIV infection – Other Radiation therapy Hodgkin’s Neoplastic Myasthenia gravis chemotherapy SLE Qualitative Think Morphology WBC Disorders Changes Graphics accessed http://us.mms.com/us/mpire/tools/download/wallpapers/2.jpg, http://www.stephengates.com/Blog/uploaded_images/unsignedUser_662.unsignedChar_1170384615063-779906.png, & http://3.bp.blogspot.com/_6B8tPuW7TwQ/Rtw2S9ud0zI/AAAAAAAACiw/tBI6crsT3nU/s400/mandm.jpg, 2009. Altered Cell Morphology • Nuclear Pelger-Huet Hypersegmentation • Cytoplasmic Alder-Reilly Chediak-Higashi May-Hegglin Gaucher Niemann-Pick Mucopolysacchridoses Toxic Granulation Think Vacuolization Neutrophilia Dohle Bodies due to Severe Bacterial Necrobiosis Infection Peripheral Blood, Wright’s, 100x. Definitions Pelger Huet vs band neutrophil • Pelger Huet – an • May-Hegglin - a rare inherited condition syndrome characterized by resulting in leukopenia, variable hyposegmentation of thrombocytopenia, granulocyte nuclei with GIANT PLATELETS, increased density and and gray-blue cytoplasmic coarseness of the inclusions in the chromatin.. Don’t confuse neutrophils and monocytes this anomaly with a [dohle-like bodies] neutrophilic left shift! Definitions • Alder-Reilly - an • Chediak-Higashi - is a inherited trait genetic disorder that has characterized by the an equivalent syndrome in mink, cattle, mice, cats, & presence of killer whales. Affected abnormally large individuals display partial azurophilic and albinism, are very basophilic granules susceptible to common resembling infectious agents, and neutrophilic toxic have white cells demonstrating giant granulation. cytoplasmic granules. Definitions • Gaucher & Niemann-Pick are • Mucopolysaccharidoses are characterized by the lack of or a group of genetically defective activity of enzymes. determined deficiencies of In Gaucher disease, there is a specific enzymes involved in lack of beta-glucocerebrosidase the degradation of and macrophages become laden mucopolysaccharides. with glucocerebrosides. Examples: In Niemann-Pick, there is deficient activity of lysosomal Hurlers hydrolase and Hunter sphingomyelinase resulting in Sanfilippo the accumulation of cholesterol and sphingomyelin in mononuclear phagocytes. Pelger-Huet & Hypersegmentation Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008. May Hegglin Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008. Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008. Alder Reilly Chediak Higashi Graphic accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, 2008. Mucopolysacharidoses Graphic accessed ttp://www.academic.marist.edu/~jzmz/topics/bloodsmears/bloodsmears27.html, 2005. Toxic Granulation & Vacuolization Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001, http://www.mclno.org/webresources/kbase/cellatlas/images/Vacuolated%20Segmented%20Neutrophil.jpg, & http://path.upmc.edu/cases/case53/images/micro2.jpg , 2008. Graphics accessed http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 & http://www.med-ed.virginia.edu/courses/path/innes/images/wcdjpeg/wcd%20dohle%20x100.jpeg, 2008. Dohle Bodies and Necrobiosis Single or multiple blue cytoplasmic inclusions. They represent remnants of rough endoplasmic reticulum from earlier maturational stages. They are associated with myeloid "left shifts" and are seen in conjunction with toxic granulation. Necrobiotic WBC displays nuclear degradation or karyorrhexis. Indicates cell death in chemotherapy or a poorly preserved specimen. (From Carr JH, Rodak BF: Clinical Hematology Atlas, 2nd ed. Philadelphia: Saunders, 2004.) Niemann Pick Graphic accessed http://www.nlm.nih.gov/medlineplus/spanish/ency/images/ency/fullsize/1224.jpg, 2001. Gaucher Graphics accessed http://www.molmed.lu.se/images/gaucher-cell.jpg & http://arttoheartweb.com/images/Van_Gogh_Starry_Night.jpg, 2001. Lymphocytosis Peripheral Blood, Wright’s, 100x. Bordatella pertussis • Whooping Cough – BUTT CELL Graphic accessed http://pathmicro.med.sc.edu/ghaffar/pertussis-lympho.jpg, 1998. Lymphocytosis • Epstein-Barr Virus – Infectious mononucleosis • Reactive/atypical/variant lymphocytes .
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