WBCs Disorders Lecture 12 PDF

Alterations in White Blood Cells Hematopoiesis 2 Functions of WBCs Mainly functions to protect against disease. Works mainly outside the blood stream Margination Rolling Adhesion Transmigration (Diapedesis) Chemotaxis Phagocytosis: Recognition, Engulfment,...

Alterations in White Blood Cells Hematopoiesis 2 Functions of WBCs Mainly functions to protect against disease. Works mainly outside the blood stream Margination Rolling Adhesion Transmigration (Diapedesis) Chemotaxis Phagocytosis: Recognition, Engulfment, Killing (digestion). Neutrophils and monocytes - most mobile and active phagocytes 3 LYSOSOMAL CONSTITUENTS PRIMARY SECONDARY  Also called azurophilic or Also called specific non - specific Lactoferrin Myeloperoxidase Lysozyme Lysozyme (Bact.) Alkaline Phosphatase Acid Hydrolases Collagenase 4  Benign disorder of white blood cells Qualitative Quantitative Morphologic changes Change in Functional changes number 5 Quantitative disorder of white blood cells leukocytosis leukopenia 6 Quantitative Disorders of white blood cells The number of leukocytes, or white blood cells, in the peripheral circulation normally ranges from 4000 to 11,000/μL of blood. The term leukopenia describes an absolute decrease in white blood cell numbers. The disorder may affect any of the specific types of white blood cells: Neutropenia Lymphopenia 7 Disorders of white blood cells The term leukocytosis describes an absolute increase in in white blood cell numbers and also may affect any of the specific types of white blood cells: Neutrophilia Eosiniphilia Basophilia Lymphocitosis Monocitosis 8 Neutropenia Neutropenia refers specifically to a decrease in neutrophils. It commonly is defined as a circulating neutrophil count of less than 1500 cells / μL. Agranulocytosis, which denotes a severe neutropenia, is characterized by a circulating neutrophil count of less than 200 cells / μL. 9  Neutropenia Congenital (Kostmann’s syndrome ) Acquired : include Accelerated removal – Inflammation , Infection Increased destruction: Drug-induced granulocytopenia Irradiation Autoimmune disorders or drug reactions Splenomegaly 10  Acquired neutropenia Felty’s syndrome A variant of rheumatoid arthritis, there is increased destruction of neutrophils in the spleen  Neoplasm's involving bone marrow (e.g., leukemia and lymphomas, myeloma)  Alcoholism  Carentiale states:  Folic acid  Vitamin B12  Iron  Cooper  Aplastic anemia  Idiopathic neutropenia 11 Neutrophilia Physiological: In newborns Pregnancy In labor Post-partum After exercise Drugs or toxics: Administration of corticosteroids - may increase the release of neutrophils from the bone marrow and reduce their migration into tissues; Acute poisoning with Hg, some venoms; 12 Neutrophilia  Reactive neutrophilia - the result of increased release of neutrophils from BM to compensate their high affinity for tissues. It is frequently accompanied by deviation to the left of the leukocyte formula (leukemoid reaction);  Metabolic and endocrine diseases: Diabetic ketoacidosis Acute renal failure Acute gout crise  In some malignant hematologic diseases: CGL, PV, CMML. 13  Eosinophilia  Allergic diseases: asthma, allergic rhinitis, eczema, atopic dermatitis  Parasitic infections  Fungal and other infections  Tuberculosis  Hematologic malignancies (CGL, AL with Eo, and nonhematologic (lung, stomach carcinoma,  Idiopathic - is diagnosis of exclusion  Drugs: aspirin, beta blockers, penicillin, cephalosporins, etc. 14  Lymphocytosis  Causes of absolute Lymphocytosis include:  Acute viral infections, such as infectious mononucleosis (glandular fever), hepatitis and cytomegalovirus infection  Other acute infections such as pertussis  Protozoal infections, such as toxoplasmosis  Chronic intracellular bacterial infections such as tuberculosis or brucellosis  Chronic lymphocytic leukemia 15  Lymphocytosis  Causes of relative Lymphocytosis include: Age less than 2 years Acute viral infections Connective tissue diseases Splenomegaly with splenic sequestration of garulocytes Exercise Stress 16 LEUCOCYTES BENIGN DISORDERS Quantitative changes (LYMPHOCYTOSIS) Infectious Mononucleosis  Epstein-Barr virus  Saliva from infected person is the main contagion  Virus infect epithelial cells and B cells.  Infection in children under the age of 10 does not cause illness and result in life long immunity  Clinical features Fever, malaise, fatigue, sore throat, diagnostic red spots at the junction of soft and hard palate, splenomegaly Blood picture shows leucocytosis ( 10 – 20 x 109/L) due to absolute increase in the number of lymphocytes Diagnosis is by serological tests. Monocytosis  Monocytosis often occurs during chronic inflammation. Diseases that produce this state:  Infections: tuberculosis, brucellosis,  Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis  Malignancies: Hodgkin's disease and certain leukaemias,  Recovery phase of neutropenia or an acute infection 18 Monocytopenia  The causes of monocytopenia include:  Acute infections  Stress  Aplastic anemia  Hairy cell leukemia  Acute myeloid leukemia  Treatment with myelotoxic drugs  Treatment with glucocorticoids 19  Basophilia  Surgical, procedure complication ( Splenectomy )  Infectious disorders (specific agent) Influenza , Chickenpox  Infected organ, abscesses  Inflammatory disorders  Neoplastic disorders: Acute myeloid leukemia ,Hodgkin's disease 20  Basophilia  Allergic, collagen autoimmune disorders  Congenital, developmental disorders  Hereditary, familial, genetic disorders (Spherocytosis )  Vegetative, autonomic, endocrine disorders (Hypothyroidism) Leukemoid reaction  Drugs Foreign protein injection 21 Qualitative disorder of white blood cells 22 PELGER-HUET ANOMALY Inherited Genetic mutation Sometimes ACQUIRED (Pseudo-PELGER-HUET) neutrophils have unusual shape (bilobed, peanut or dumbbell-shaped NOT serious, mostly a cute incidental finding 23 CHEDIAK-HIGASHI SYNDROME Also genetic Abnormal large irregular neutrophil granules Impaired lysosomal digestion of bacteria Associated with pigment and bleeding disorders can be serious, especially in kids 24 Chronic granulomatous disease (CGD) The abnormal neutrophils phagocytosis microorganism but do not kill them due to: Lack of respiratory burst. Lack of peroxidase production.  Leukocyte adhesion deficiency LAD) It is autosomal recessive disorder. Characterized by absence of leukocyte cell-surface adhesion proteins (integrins), the CD 11/CD18 complex. CD11/CD18 are important in cell motility, transendothelial migration, and serve as receptors for complement  mortality rate in childhood is high. Patients with LAD their neutrophils is defective in:  adhesion to endothelial.  Chemotaxis.  C3bi mediated phagocytosis.  Particle- triggered respiratory burst activation.  Degranulation. Clinical finding in LAD  frequent bacterial and fungal infection. Lack of pus formation. Delayed separation of the umbilical cord. There is persistent leukocytosis. Diagnosis is by flow cytometric analysis of neutrophil CD11/CD18 level.