wight blood pathology - rsmu.ru
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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 NUMBER x109 /L
PER sent %
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 ← - allergy, - atopic diseases, - neoplasms, - chronic paracitic invasion, - dermatologic disorders LYMPHOCYTOSIS ← - acute viral infection, - hepatitis, - typhoid, - thyrotoxicosis, - adrenal insufficiency - infectious mononucleosis
EOSINOPHYLIA
LYMPHOCYTOSIS
Infections:
Allergic drug reactions Hyper thiroidism Splenectomy Serum sickness disease
NON – MELIGNANT CAUSES OF LYMPHOSITOSIS
Viral infections : - Infection mononucleosis - SPRU , Rubella, Pertusis, Viral hepatitis Bacterial infections: -Tubercullosis, Brucellosis, - Typhoid fever Protosoal infections
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 - increased NP destruction in the circulation by some drugs. Cytotoxic type (11) of hypersencitivity
MYELOTOXIC form – suppression of hemopoiesis in the bone marrow by many factors.
AGRANULOCYTOSIS IMMUNE FORM MYELOTOXIC FORM
- Leukemia due to increased destruction of granulocytes in blood. - ↓ granulocytes ------------------------- ------------------------ - relative lymphocytosis -------------------------- --------------------------- Infection, septicemia, fever, tachycardia, ulcer in mouth
- Leukemia (pancytopenia) due to decreased bone marrow production -↓ granulotes, -- ↓ erythrocytes (anemia) - ↓ platelets (thrombocytopenia) - relative lymphocytosis - partial hypoplasia of bone marrow - Fat tissue > than blood cells 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., HEMORRAGIC s., HYPERPLASTIC s., INFECTIOUS s., TOXIC s.
Blood picture
THE LEUKEMIAS
ACUTE - ANEMIA - THROMBOCYTOPENIA - BLAST CELLS > 30% - ABSENT of INTERMEDIATE cells of THIS LINE in peripheral blood “hiatus leukemicus”
CHRONIC - ANEMIA - THROMBOCYTOPENIA - BLAST CELLS < 1 % - ALL CELL IN THIS LINE are in peripheral blood
Classification of acute myeloid and lymphoid leukemias
ACUTE MYELOBLASTIC L Mo (AML) Undifferenciated
CD 13, CD33 CD 34
All cytochemical reactions are negative “-”
ACUTE MYELOBLASTIC L. without maturation M1, M2
CD13, CD33 Myeloperoxidase, “+” lipid ( sydan black) “ +”
ACUTE PROMYELOCYTIC L. M3 CD 13, CD33 MP “+”, Lipid “+”
ACUTE MYELOBLASTIC L. M4 CD 13, CD 33 CD 11, CD14
MP “+”, 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
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 – is a condition in which there is hemoconcentration of the blood accompaned by dehydration.
Absolute P - consists of: Primary form and Secondary form.
The Absolute primary form of 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