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Wight Blood Pathology WHITE BLOOD PATHOLOGY Alteration of leukocytes function, leukemia Normal distribution of white blood cells Total white cells count 4,0 – 11,0 x 10 9/L CELL ABSOLUTE PER sent % NUMBER x109 /L Neutrophils 2,5 – 7,5 58 - 72 BAND cells 0,04 – 0,4 1 - 6 Lymphocytes 1,5 – 4,0 19 -37 Monocytes 0,2 – 0,8 3 - 11 Eosinophils 0,04 – 0,4 1 - 6 Basophiles 0,01 – 0,1 0,5 - 1 Calculation of absolute or relative leukocytosis Example: Blood examination: Leukocytes – 1,5 x 109 /l segmented neutrophils – 15% Lymphocytes - 70% Estimate the absolute amount of neutrophils and lymphocytes Total amount of leukocytes 1,5 x 109 - 100% neutrophils X - 15% X= ( 1,5 x 109 x 15 ) : 100 = 0,225 x 109 ( 2,5 – 7,5 x109 ) Absolute neutropenia Total amount of leukocytes 1,5 x 10 9 - 100% lymphocytes X - 70% X = ( 1,5 x 109 x 70 ): 100 = 1,05 x 10 9 ( 1,5 – 4 x 10 9 ) Relative lymphocytosis Leukocytosis - ↑amount of L > 9 x 10 9 /L NEUTROPHILIA ← Causes: - infection, - APR, - tissue injury - hemorrhage, - neoplasm, - metabolic disorders, - stress states, - inflammation, - severe colic, - glucocorticoid administration. MONOCYTOSIS ← -chronic infection: tuberculosis, lepra, siphilis, malaria, rikketsiosis, endocarditis - infection mononucleosis, - vasculitis, - collagen disease EOSINOPHYLIA ← - allergy, - atopic diseases, - neoplasms, - chronic paracitic invasion, - dermatologic disorders LYMPHOCYTOSIS ← - acute viral infection, - hepatitis, - typhoid, - thyrotoxicosis, - adrenal insufficiency - infectious mononucleosis LYMPHOCYTOSIS NON – MELIGNANT CAUSES OF LYMPHOSITOSIS Infections: Viral infections : - Infection mononucleosis - SPRU , Rubella, Pertusis, Viral hepatitis Bacterial infections: -Tubercullosis, Brucellosis, - Typhoid fever Protosoal infections Allergic drug reactions Hyper thiroidism Splenectomy Serum sickness disease LEUKOPENIA - ↓ amount of L < 4 x 10 9 /L NEUTROPENIA ← decreased bone marrow production: - radiation, - chemotherapy, - leukemia, - aplastic anemia, - abnormal granulopoiesis increased destruction: - splenomegaly, - hemodialysis, - immune reaction infection: - gram-negative (thyphoid), - viral (influenza, mumps) - protozoa (malaria) EOSINOPENIA stress response, trauma, shock, burns, drugs, steroids (Cushing syndrome) BASOPENIA: pregnancy, - stress, -Graves disease LYMPHOPENIA - immune deficiency, AIDS, - agammaglobulinemia, - lymphocyte destruction (GC), -malignacies, - diseases: aplastic anemia, heart failure, TB AGRANULOCYTOSIS Agranulocytosis - syndrome , which characterized by granulocytopenia ( neutropenia less then 0,75 x 10 9/l ) during severe leukopenia ( 1-3 x 109 /l ) IMMUNE form - MYELOTOXIC form – increased NP destruction suppression of in the circulation by hemopoiesis in the some drugs. bone marrow by many Cytotoxic type (11) of factors. hypersencitivity AGRANULOCYTOSIS IMMUNE FORM MYELOTOXIC FORM - Leukemia due to - Leukemia (pancytopenia) increased destruction of due to decreased bone granulocytes in blood. marrow production - ↓ granulocytes -↓ granulotes, ------------------------- -- ↓ erythrocytes (anemia) ------------------------ - ↓ platelets (thrombocytopenia) - relative lymphocytosis - relative lymphocytosis -------------------------- - partial hypoplasia of --------------------------- bone marrow Infection, septicemia, fever, - Fat tissue > than blood cells tachycardia, ulcer in mouth Infectious diseases, hypoxic syndrome, hemorrhagic syndrome Ulcer nerotic tonsilitis Agranulocytosis Immune form (Blood smear) Myelotoxic form (bone marrow) Treatment of agranulocytosis - monitoring with serial blood counts - withdrawal of offering agent (e.g. Medications) - Transfusion of granulocytes. However, granulocyte live only ~10 hours in circulation; for days – in Spleen , which gives a shot-lasting effect - Myelotoxic form of agranulocytosis treats the same as aplastic anemia : infusion of erythrocytic and thrombocytic mass , stimulation of hemapoiesis by erythropoietin, cytokines hormones. Transplantation of bone marrow . The Leukemias The group of malignant disorders in which abnormal proliferation of hemopoietic cells with signs of abnormal maturation that cause progressive infiltration of bone marrow and lymph nodes The theoretical causes: viral cancerogenesis, chemical cancerogenesis, irradiation, hereditary PATHOGENESIS: Activation of protooncogenes →suppresion of antioncogenes→ Incline with DNA reparation genes, week the apoptic genes action → provide uncontrolled DNA replication The leukemias Hemoblastosis are systemic disorders of hemopoietic tissue which characterized by malignant nature. HEMOBLASTOSiS: 1. Acute leukemia: acute myeloblastic leukemia acute lymphoblastic leukemia (B-ALL, T-ALL, preB-ALL) 2. Chronic myeloprolipherative diseases : chronic myelocytic leukemia, polycythemia Vera, essential thrombocytopenia 3. Chronic lymphoproliferative disorders: chronic lymphocytic leukemia, Lymphomes LEUKEMIA. CLINICAL SYMPTOMS HYPOXIC S., THE LEUKEMIAS HEMORRAGIC s., HYPERPLASTIC s., INFECTIOUS s., TOXIC s. Blood picture ACUTE CHRONIC - ANEMIA - ANEMIA - THROMBOCYTOPENIA - THROMBOCYTOPENIA - BLAST CELLS > 30% - BLAST CELLS < 1 % - ABSENT of INTERMEDIATE - ALL CELL IN THIS LINE cells of THIS LINE in are in peripheral blood peripheral blood “hiatus leukemicus” Classification of acute myeloid and lymphoid leukemias ACUTE MYELOBLASTIC L Mo CD 13, CD33 All cytochemical reactions (AML) Undifferenciated CD 34 are negative “-” ACUTE MYELOBLASTIC L. without CD13, CD33 Myeloperoxidase, “+” maturation M1, M2 lipid ( sydan black) “ +” ACUTE PROMYELOCYTIC L. M3 CD 13, CD33 MP “+”, Lipid “+” ACUTE MYELOBLASTIC L. M4 CD 13, CD 33 MP “+”, CD 11, CD14 Specific esterase “+” ACUTE MONOCYTIC L M5 CD 11, CD14 Specific esterase”+” ERYTHROLEUKEMIA M6 CD 13, CD33 PAS-reaction “+” glycog en diffused form ACUTE LYMPHOBLASTIC L CD10, CD19 MP “-”, Lipid “-” PAS-REACTION “+” glycogen granular form CELLULAR MARKERS OF ACUTE LEUKEMIA STEM CELLS MYELOID cells MONOCYTES MEGACARIOCYTES B – CELLS T - CELLS ACUTE LEUKEMIA BLOOD cells in the BONE MARROW Normal Myeloblastic L Lymphoblastic L - Granulocytopenia ACUTE LYMPHOBLASTIC LEUKEMIA LYMPHOID INFILTRATION OF BONE MARROW ACUTE LYMPHOBLASTIC LEUKEMIA BLOOD SMEA ACUTE MYELOBLASTIC LEUKEMIA BONE MERROW MYELOBLASTIC LEUKEMIA> BLOOD SMEAR MYELOBLASTIC LEUKEMIA Peripheral blood Myeloblast POSITIVE CYTOCHEMICAL REACTION TO MYELOPEROXIDASE All the cells from myeloid granulocytic line colour the cytoplasm in yellow POSITIVE PAS reaction to GLYCOGEN In lymphoblasts –glycogen in granules Positive PAS reaction to glycogen in LYMPHOCYTE LINE NEUTROPHIL LINE Granular form of glycogen Diffused form of glycogen CHRONIC LEUKEMIA PERIPHERAL BLOOD SMEARS Normal blood Chronic lymphocytic Chronic myelocytic LEUKEMIA LEUKEMIA CHRONIC LYMPHOCYTIC LEIKEMIA Peripheral blood “ Smudge cells”- Humprecht shadows Lymphocytic lysis appear in blood smear CHRONIC LYMPHOLEUKEMIA . Lymphoid hyperplasia of spleen Lysis of lymphocytes ( H-B shadow) CHRONIC LYMPHOCYTIC LEUKEMIA LYMPHOIDAL METHAPLASIA of BONE MARROW Lymphoblast Lymphocyte PHILADELPHIA chromosome CHRONIC MYELOCYTIC LEUKEMIA. Peripheral blood CHRONIC MYELOCYTIC LEUKEMIA Blood smear Treatment of leukemias - Chemotherapy - Immunotherapy agents that induce differentation of immature granulocytes. - Transplantation of bone marrow - Supportive measures include blood transfusion, antibiotics, antifungals, antiviral LEUKEMOID REACTIONS POLYCYTHEMIA - a groop of disorders which characterized by an excess of red cell production Relative P – Absolute P - consists of: is a condition in which Primary form and there is Secondary form. hemoconcentration of the blood accompaned The Absolute primary form of by dehydration. polycythemia is known as polycythemia vera. Secondary P. is the most common and is a physiological response to hypoxia caused by ↑ secretion of erythropoietin. Causes: in individuals who live at higher altitudes, individuals with COPD, heart failure, abnormal Hb, renal cell carcinoma, hepatoma POLYCYTHEmIA VERA Vaquez’s disease POLYCYTHEMIA VERA is a neoplastic, nonmalignant myeloproliferative disease, which characterized by abnormal proliferation of bone marrow stem cell despite normal to below normal erythropoietin level The most likely cause of PV is acquired genetic alterations in the stem cell leading to disturbance of normal cellular growth. CLINICAL MANIFESTATION : ↑Er, ↑BP, ↑Ht, ↑viscosity, ↑thrombosis, hemorrhagies, pletora, visual dusturbance, myocardial infarction, Splenomegaly, hepatomegaly, skin itching POLYCYTHEMIA VERA Bone marrow Peripheral blood Polycyhtemia Vera: clinical symptoms POLYCYTHEOMIA VTRA TREATMENT Controlling in number of Er, Ht, BP Plobotomy Frequent plobotomies reduce Fe (iron) → ↓Er Radioactive phosphorus → ↓ erythropoiesis Chemotherapy .
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