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.

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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

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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

- 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

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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