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HEMATOLOGY. Hematopoiesis n Fetus: liver, spleen, bones sometimes regain heatopoietic activity in the adult: i.e. myelofibrosis n Child: long bones, skull,

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Presentation on theme: "HEMATOLOGY. Hematopoiesis n Fetus: liver, spleen, bones sometimes regain heatopoietic activity in the adult: i.e. myelofibrosis n Child: long bones, skull,"— Presentation transcript:

1 HEMATOLOGY

2 Hematopoiesis n Fetus: liver, spleen, bones sometimes regain heatopoietic activity in the adult: i.e. myelofibrosis n Child: long bones, skull, vertebrae etc. n Adult: vertebrae, sternum, ribs, pelvic bones and long bones, skull - about 1 kg tissue producing cells/day

3 Hematopoietic cells n Pluripotent stem cell compartment – relatively small, lymphocyte-like cells n Proliferating cells of committed lineage myeloid, erythroid, megakaryocyte, lymphoid, reticulum cell lines n Maturing (postmitotic) cells n Mature cells circulating half life: pmn.leukocytes 6 hours platelets: 8-10 days erythroid cells: 120 days

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5 Erythropoiesis n Stimulus: hypoxia erythropoietin ( in the kidney [and liver]) pluripotent stem cells CFU-E BFU-E proerythroblasts erythroblasts normoblasts mature red blood cells

6 Leukocyte production n Pluripotent stem cells n Myeloblasts n Promyelocytes n Myelocytes

7 Leukocyte production Metamyelocyte

8 Leukocyte production Band-form

9 Leukocyte production Mature polymorphonuclear granulocyte

10 Megakaryocyte line Giant, multinucleated cells Breaks up, releasing about 5000 platelets

11 Marrow lymphocytes arising also in spleen and lymph nodes lifetime: years

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13 Bone marrow function n Hematopoiesis n Antibody producing plasma cell differentiation n Monitoring hematopoietic cell quality n Important key nutrients: iron folic acid vitamin B12 regulatory hormones (EPO, CSF-s) interleukins

14 Hematological diseases

15 Anemia n Decrease in red cell mass or hemoglobin content of blood below the physiologic need n Not a disease itself! A clinical sign! n Analysis of anaemia – seek the background mechanisms n loss of red blood cell - bleeding n lack of red blood cell production n excessive red blood cell damage

16 History n Family history: anemia, splenomegaly, jaundice n Bleeding tendency in the family n Diet, alcohol intake n Menorrhagia n Drugs n Chronic diseases n Malnutrition, malabsorption n Transfusion, iron or other therapy against anemia

17 Anemia n Signs and symptoms vary with the rapidity of onset: n Rapid (bleeding or brisk hemolysis) – cardiovascular compensatory reactions: tachycardia, postural hypotension, vasoconstriction in the skin and extremities, dyspnea on exertion, faintness, even shock n Slowly developing anemias (ie.nutritional deficiency, chr.bleeding, hemolysis etc.) – there is time for compensation – the patient remains asymptomatic for a long time

18 Anemia n Mild: often asymptomatic n Moderate: symptoms on exertion n Severe: symptoms on rest heart failure

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20 Anemia - physical findings Non cause-specific n Pallor of skin and mucous membranes – causes: Hb  and blood redistribution from the skin – colors n greyish: malignancy n lemon-like: hemolysis, B12 deficiency n Tachycardia n Hyperkinetic precordium n Systolic murmur (reversible)

21 Anemia - physical findings Cause-related n Jaundice hemolysis n Hepatosplenomegaly - e.g.hemolysis n Lymphadenopathy - lymphomas, autoimmune diseases n Cheilosis (fissura) iron deficiency n Koilonychia (spoon-shaped nails) iron def. n Beefy red smooth tongue (Hunter- glossitis) - pernicious anemia n Neuropathy - pernicious anemia n Rectal digital examination - bleeding

22 Laboratory evaluation of anemia n Complete blood picture n Red cell indices n red blood cell count F:3,9-5,6, M:4,5-6,5 G/l n hemoglobin level F: M: g/l n hematocrit F:36-48 M:40-52% n MCV: mean corpuscular volume fl n MCH mean corpuscular hemoglobin pg n MCHC: mean corpuscular hemoglobin concentration g/l n Reticulocyte count (traces of endoplasmic reticulum) - good marker of erythropoiesis 0,5-1,5%

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29 MCV n Microcytic anemia (MCV<80 fl) iron deficiency, thalassemia, sideroblastic anemia n Normocytic anemia (MCV fl) acute bleeding, renal failure, aplastic anemia n Macrocytic anemia (MCV>100 fl) vitamin B12, folic acid deficiency, liver disease, alcoholism, hypothyroidism

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32 MCH n Hypochromic (MCH<27 pg) – Iron deficiency(i.e. chr. bleeding, malabsorption) – chr. inflammation, malignancy, chr. infection, thalassemias, myelodysplastic sy. n Normochromic (MCH pg) – acute bleeding, hemolysis, aplastic anemia, renal anemia n Hyperchromic (MCH>34 pg) – megaloblastic anemia (B12, folic acid deficiency)

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36 Clinical classification of anemias n Decreased cell production – Aplastic anemia – Myelodysplastic syndrome – Deficiency anemias (iron, B12, folic acid) – Erythropoietin deficiency (renal failure) – Bone marrow suppression (malignancy, toxin,virus) n Increased red blood cell destruction/elimination – Extrinsic factors (immun, toxins, mechanic) – Membrane defects – Enzyme defects – Hemoglobinopathy n Blood loss (genitourinary, gastrointestinal, pulmonary other bleeding)

37 Bone marrow investigation Bone marrow biopsy or aspiration n bone marrow cellularity n myeloid-erythroid ratio (norm: 2-3:1) n cell maturation n bone marrow infiltration n stromal cells (fibroblasts etc.)

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42 Polycythemias n Hyperviscosity – Decreased cerebral blood flow tinnitus, lightheadedness, dizziness, stroke – Congestive heart failure – Thrombosis n Increased cell turnover – Gout (due to hyperuricemia) – Itching n In polycythemia vera – Thrombocytosis – Hemorrhage

43 Polycythemias n Primary: polycythemia vera myeloproliferative disorder – other cell lines are affected (leukocytosis, thrombocytosis) – hepatosplenomegaly – EPO level: low n Secondary: – hypoxia EPO production n chr. pulmonary diseases n morbid obesitiy (Pickwick’s syndrome) n high altitude – EPO overproduction: tumors

44 Leukocyte disorders 1. Benign alterations 2. Malignant diseases

45 Neutrophil granulocytes n Functions: n chemotaxis n phagocytosis n microbial killing n Disorders n neutropenia, agranulocytosis: abs.count<1000 causes:drugs, autoimmun diseases, viral infections (e.g. EBV,HIV,hepatitis), B12 deficiency, leukemias,alcoholism increased risk of infection n neutrophilia:infections, stress, drugs (steroids) n left shift: bacterial infections

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48 Mononuclear phagocytes monoblasts, promonocytes, monocytes, tissue macrophages n Functions n chemotaxis n ingestion and killing microorganisms n secretion of several factors proteases, cytokines, reactive oxygen compounds, colony stimulating factors n interaction with lymphocytes n antigen processing and presentation

49 Eosinophil granulocytes n Eosinophilia: n Parasitic infections n Allergies n Autoimmune diseases n Hematologic malignancies (CML, Hodgkin’s disease etc.)

50 Basophil granulocytes n Important role in: – inflammation – hypersensitivity reactions n Basophilia: malignant hematologic diseases

51 Acute leukemias n Agressive immature hemopoietic cell proliferation, without differentiation (hiatus leucemicus in the blood smear) – Subtypes: n ALL (acute lymphoblastic leukemia) n ANLL (acute non lymphoblastic leukemia) or AML (acute myeloblastic leukemia)

52 Acute leukemia syndrome n Susceptibility to infections - serious infections n Anemia due to bone marrow infiltration and bleeding n Thrombocytopenia - bleeding tendency purpuras, petechiae, mucosal bleeding n Organ infiltration

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55 Chronic leukemias n Uncontrolled expansion of premature hemopoietic cells which are able to differentiate n Subtypes: – Chronic myelogenous leukemia (CML or CGL) a myeloproliferative disorder – Chronic lymphocytic leukemia (CLL) a malignant lymphoma

56 CML n Abnormal blood count n Organomegaly (hepato)splenomegaly

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60 CLL n Old patients n Blood count abnormalities n Leukocytosis n Lymphocytosis (small, mature lymphocytes) n In advanced disease: anemia, tct-penia n Generalised lymphadenopathy n Splenomegaly n Susceptibility for infections (pneumonia) n Sometimes hemolytic anemia n Immundeficiency

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63 Evaluation of leukemias n Complete blood picture n Bone marrow investigation n Cytochemistry n Immunochemistry n Genetic alterations n chromosomal aberrations n gene anomalies

64 Chronic myeloproliferative disorders n Polycythemia vera n Myelofibrosis with myeloid metaplasia n Essential thrombocythemia n Chronic myelogenous leukemia

65 Diseases of the lymphoid system n Normal lymph nodes – Non palpable or <1 cm, except in the inguinal region where can be 0,5-2 cm sized lymph nodes normally – Small lymph nodes can be remain after infection – Significant: one or more new nodes >1 cm (which can’t explain by a previously recognised cause) – New lymph nodes in older age more significant n children more likely respond with lymphoid hyperplasia n lymphyadenopathy under 30 years: 80% benign over 50 years: 40% benign

66 Causes of lymphadenopathy – (1) increase in the number of benign lymphocytes and macrophages during response to antigens – (2) infiltration by inflammatory cells in infections (lymphadenitis) – (3) in situ proliferation of malignant lymphocytes or macrophages – (4) infiltration of nodes by metastatic malignant cells – (5) infiltration of lymph nodes by metabolite-laden macrophages in lipid storage diseases

67 Lymph node characteristics n Location n Number (single, multiple, matted together) n Size n Tenderness n Consistency (hard, rubbery, soft) n Mobility n Skin reactions above the lymph node

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69 Lymphadenopathy- by region – Cervical in young adult: infectious mononucleosis – Unilateral epitrochlear : hand infections – Bilateral epitrochlear : sarcoidosis, tularemia, syphilis – Unilateral axillary: breast carcinoma, lymphomas, infections of the upper extremities, cat-scratch disease, brucellosis – Bilateral inguinal: venereal infections – Unilateral inguinal: lymphogranuloma venereum, syphilis – Progressive inguinal lymph node enlargement without obvious infection: malignant disease.

70 Lymphadenopathy- by region – Posterior cervical, occipital: scalp infections, toxoplasmosis, rubella – Anterior auricular: infections of the eyelids and conjunctiva – Lymphomas often involve cervical lymph nodes and occasionally involve posterior auricular and occipital nodes – Enlarged suppurative cervical nodes: mycobacterial lymphadenitis (scrofula) – Unilateral jugular or mandibular lymph node: lymphoma or head and neck malignancy – Supraclavicular (always significant): metastasis from intrathoracic, breast, gastrointestinal malignancies (Virchow’s lymph node) or lymphoma

71 Lymphadenopathy- by region Hilar or mediastinal – Symptoms: cough,wheezing, hoarseness, paralysis of the diaphragm, dysphagia – Bilateral mediastinal: lymphomas – Unilateral hilar: metastatic carcinoma (usually lung) – Bilateral hilar: sarcoidosis, tuberculosis, fungal infections, lymphomas Retroperitoneal, intraabdominal: lymphomas, metastases, rarely inflammatory ( Tuberculosis can cause mesenteric lymphadenitis with large matted and sometimes calcified nodes) Generalised: lymphomas (CLL), systemic infections (tbc), autoimmune diseases

72 Lymphadenomegaly Diagnostic evaluation n Complete blood picture n Chest x-ray n Ultrasonography (abdominal, cervical, axillar etc.) n CT-scan n Fine needle biopsy- cytology n Lymph node excision

73 Splenomegaly - causes – (1) Reticuloendothelial or immune system hyperplasia infectious diseases immune diseases (Felty's syndrome - RA) abnormal red blood cell destruction: hereditary spherocytosis, thalassemia, sickle cell disease – (2) Altered splenic blood flow (congestion): hepatic cirrhosis, splenic, hepatic, or portal vein thrombosis – (3) Malignant neoplasms: primarily: lymphomas secondarily: leukemias, metastatic solid tumors

74 Splenomegaly – (4) Extramedullary hematopoiesis in the spleen: myeloid metaplasia – (5) Infiltration of the spleen with abnormal material: amyloidosis, Gaucher's disease – (6) Space-occupying lesions of the spleen: hemangiomas, cysts

75 Splenomegaly – Mild: congestive heart failure, malaria, typhoid fever, bacterial endocarditis, systemic lupus erythematosus, rheumatoid arthritis, thalassemia minor – Moderate: hepatitis, cirrhosis, lymphomas, infectious mononucleosis, hemolytic anemias, splenic abscesses and infarcts, amyloidosis – Massive: chronic myelocytic leukemia, myeloid metaplasia with myelofibrosis, hairy cell leukemia, Gaucher's and Niemann-Pick diseases, sarcoidosis, thalassemia major, chronic malaria, congenital syphilis, leishmaniasis, portal vein obstruction

76 Splenomegaly Diagnostic evaluation n Complete blood picture n Serology (infections, autoantibodies) n Blood culture n Imaging technics (chest x-ray, ultrasonography, Doppler US, CT, MR) n Histology

77 Malignant lymphomas n Arise in lymph nodes or extranodal lymphoid tissue n Subtypes: – Hodgkin’s disease – Non Hodgkin’s lymphomas

78 Hodgkin’s disease n Mostly young adults n Asymptomatic lymphadenopathy – often cervical – mediastinal – abdominal n Hepatomegaly, splenomegaly n Fever, night sweats, loss of weight n Diagnosis: lymph node histology (Reed-Sternberg cells) Staging

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80 Non Hodgkin’s lymphomas n Older patients n More diffuse lymph node involvement n General symptoms:fever, weight loss, night sweat n Frequent extralymphatic involvement (50%: bone marrow  anemia, tct-penia) n Special forms: CLL Skin infiltration (T-cells) MALT-lymphoma Multiple myeloma

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82 n Plasma cell neoplasm n Bone marrow infiltration n Monoclonal immunglobulin production n Osteolytic lesions, bone pain n Renal lesion

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85 Coagulation disorders Bleeding tendency, thrombosis, embolism Factors n platelets (number, function) n coagulation factors (amount, function) n surface of the blood vessels, circulation

86 Bleeding - history n History of common hemostatic stresses: n gum extraction, minor surgeries n menstruation, childbirth n injuries n Family history of bleeding tendency

87 Bleeding n Primary hemostatic defect (platelets) n occurs immediately after trauma n from superficial sites (skin, mucous membranes, nose, rarely from gastrointestinal, genitourinary tract) – purpuras, petechiae – ecchymoses n bleeding time  n Secondary hemostatic defect (coagulation) n delayed occurence (hours, days) n from deep sites (joints, subcutaneous tissues, muscles, retroperitoneum, body cavities, cerebrum) – hematomas – hemarthroses n coagulation time 

88 Bleeding - physical findings n From capillaries: purpuras, petechiae small, superficial,dermal or mucosal pinpoint hemorrhages characteristic for platelet disorders n From small arterioles and venules: – ecchymoses subcutaneous blood collections- bruises – hematomas deeper, palpable – in platelet and coagulation disorders n Hemarthros - bleeding into joints characteristic for coagulation disorders (mostly hemophilia) leads to chronic joint deformity

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91 Thrombosis and embolism n Virchow’s triad – Hypercoagulability – Circulation disturbance- congestion – Pathological endothelial surface

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95 Hemato_Proped.ppt Hemato_Proped.doc

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