Blood And Lymphatic System PDF

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  predominit icalers to meet ~ w **...

Blood and Lymphatic System Dr. Raya D. Marji, M.D. Al-Balqa Applied University Office: O505  predominit icalers to meet ~ w ** MMDS Y N All  Myeloproliferative Neoplasms (MPN): I Acquired malignant clonal disorders of pluripotent stem cells with resulting abnormalities in one or more cell lines. Initially, the clonal stem cells retain their capacity to terminal 8 - Mature Bells differentiations1&1 -89948558, i differentiation. Mutated, constituently active tyrosine kinases or other acquired I aberrations in signaling pathways that lead to growth factor independence. Cell $ proliferation (1.3 95 Major diagnostic entities: 1. Chronic myeloid leukemia (CML) 2. Polycythemia vera 3. Essential thrombocythemia 4. Primary myelofibrosis  58, s Nonfunctional 11 I... Nonfunctional platelet M ~ & fusion * I S 95 $58615 sis $ · is?s! => Is sphenomegaly Megakaryocyle - WBC SBM six) fibrosis 55.315,95: - josss Redpulpsids Callis& 39 2.54 blood vesself; 6? RBCs Dess? Bi s * -> & spleens! i 251 s 56: erythropoietings - hypoxia is liver sis & & I d 510 &$128 -5 E.3 calls. 5 :BMSIS.3 S Blusts. 1. Chronic Myeloid Leukemia (CML) Massive overproduction of normal-appearing granulocytes. Adults between 25 and 60 years (peak in 4th -5th decades). Pathogenesis: - In about 95% of cases, there is a t(9;22) (Philadelphia chromosome) that results in a chimeric BCR-ABL gene which encodes a fusion protein with tyrosine kinase activity. The mutation is a stem cell mutation (found in granulocytes, erythroid, megakaryocytes, B and T precursors); however, the effect is limited to granulocyte and megakaryocyte.  Clinical Features The onset is insidious. The initial symptoms usually are nonspecific (e.g. anemia with fatigue, weakness, anorexia, night sweat, weight loss, Bleeding tendencies, Infections). Dragging sensation in the abdomen caused by splenomegaly. Chronic Myeloid Leukemia (CML): Laboratory Findings: Elevated leukocyte count (often exceeding 100,000 cells/μL). The circulating cells are predominantly neutrophils and immature forms, but basophils and eosinophils are also prominent. High platelet counts (early), thrombocytopenia (late). Mild to moderate anemia. Differential diagnosis: Leukemoid reaction. Other MPN. CML—peripheral blood smear: Granulocytic forms at various stages of differentiation are present Chronic Myeloid Leukemia (CML) Pathology: Bone marrow: - Markedly hypercellular - Mild reticulin fibrosis. Spleen: - Expanded red pulp with extramedullary hematopoiesis (compromises the local blood supply, leading to splenic infarcts). Chronic Myeloid Leukemia (CML)  Course and Prognosis Slow progression of 3 phases: 1- Chronic phase: - 1-5 years - Mild anemia – Blasts 2- Accelerated phase: - Increasing anemia - New thrombocytopenia - Additional cytogenetic abnormalities - 10 - 19% blasts in BM 3- Blast crisis: - 20% blasts (definition of acute leukemia) - Abrupt or gradual over weeks. Less commonly, CML progresses to a phase of extensive bone marrow fibrosis resembling primary myelofibrosis (Spent phase).  is ess ↓ asix Not suppressing -6 - - ~ sitss blackstool -I ~ 6 -is -91's rising 6s eythropoietinsia'si 2. Polycythemia Vera (PV) Insidious clonal disorder of pluripotential hematopoietic stem cells dominated by an expansion of the red cell mass. Activating mutations in the tyrosine kinase JAK2. Excessive proliferation of erythroid, granulocytic, and megakaryocytic elements. Most clinical signs and symptoms are related to an absolute increase in red cell mass. Associated with low levels of serum erythropoietin. Must be differentiated from secondary polycythemia. Be failure Clinical findings Appears insidiously, usually in late middle age. Most manifestations are related to expanded blood volume, increased blood viscosity (hematocrit > 55%), thrombotic and hemorrhagic tendencies: Plethoric and somewhat cyanotic. Headache, weakness, hypertension, gastrointestinal symptoms (hematemesis, and melena). Pruritus. Splenomegaly. Hepatic vein thrombosis giving rise to Budd-Chiari syndrome.  Laboratory Findings: - High red cell counts - High hematocrit - High granulocyte count - High platelet count - Basophilia is common – iron deficiency anemia Pathology Bone marrow: - Hypercellular - Some degree of marrow fibrosis - Hepatosplenomegaly - Organs thromboses and infarctions  (Non platelet) functional ↓ Sistemisinisschema s 5 3.Essential Thrombocythemia (ET) A clonal stem cell disorder characterized by elevated platelet counts. Sustained Platelet count > 450,000 /µl 2. Hyperplasia of large mature marrow megakaryocytes with NO significant granulopoiesis or erythropoiesis. JAK2, MPL or another clonal marker. Clinical Findings: Age > 60 yrs. Hemorrhage or thrombotic episodes. j 1 Gastrointestinal bleeding and epistaxis. Venous or arterial thrombosis. Pain in palms, soles and toes (erythromelalgia). Pathology Bone marrow: - Mild cellularity. - Megakaryocytes are often markedly increased in number and include abnormally large forms. Peripheral smears: - Large platelets, extramedullary hematopoiesis may occur (mild organomegaly). s -55 s RBC WBC is s 4. Primary Myelofibrosis A chronic myeloproliferative disorder characterized by: - Bone marrow fibrosis. - Reduce bone marrow hematopoiesis and cytopenia. - Splenomegaly and extramedullary hematopoiesis. Fibrosis is caused by the inappropriate release of fibrogenic factors from neoplastic megakaryocytes (platelet-dervied growth factor and TGF).  Morphology Peripheral blood: - Leukoerythroblastosis (Red cells exhibit bizarre shapes (poikilocytes, teardrop cells), and nucleated erythroid precursors along with immature white cells (myelocytes and metamyelocytes)). - Abnormally large platelets. Bone marrow: - In advanced cases is hypocellular and diffusely fibrotic. - Megakaryocytes are present in clusters and have characteristic hyperchromatic nuclei with “cloudlike” outlines. E Myelodysplastic Syndromes (MDS) A preleukemic disorder with a cytopenia in the peripheral blood. Characterized by: - Ineffective hematopoiesis (bone marrow failure) and high risk transformation to AML. - Hypercellular bone marrow (might be normocellular). - Peripheral pancytopenia. Idiopathic or secondary to radiation and alkylating chemotherapy.  Pathogenesis: - Mutations in transcription factors, RNA splicing factors and Epigenetic factors. - 10% of MDS cases have loss-of function mutations in TP53. - Recurrent chromosomal abnormalities, including deletions of 5q, 7q, and 20q, and trisomy 8. Clinical features: - Ages of 50 to 70 yrs. - Infections, symptoms related to anemia or hemorrhage. ❖ Morphology The marrow is populated by abnormal-appearing hematopoietic precursors: - Megaloblastoid erythroid precursors. - Erythroid forms with iron deposits within their mitochondria (ring sideroblasts). - Granulocyte precursors with abnormal granules or nuclear maturation. - Small megakaryocytes with single small nuclei or multiple separate nuclei.  CBC shows cytopenia with increased MCV. Bilobed nucleus of neutrophil (pelger-huet cell)