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Hematopoietic System- 1 Bone Marrow Hematopoiesis. Linda F. Cunningham, MD January 2, 2003. Hematopoietic System Bone Marrow. Hematopoietic active marrow with stem cells, progenitor cells, and developing erythroblasts, myeloblasts, and megakaryoblasts (red marrow)
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Hematopoietic System- 1Bone Marrow Hematopoiesis Linda F. Cunningham, MD January 2, 2003
Hematopoietic SystemBone Marrow • Hematopoietic active marrow with stem cells, progenitor cells, and developing erythroblasts, myeloblasts, and megakaryoblasts (red marrow) • Adipose cells, various with age and activity (yellow marrow) • Marrow sinuses and capillary network
Slide • ASCP Bone Marrow 3: • Histology 6.2: Trabecular bone with hematopoietic tissue and fat • Rodak 7 Bone Marrow with hematopoietic tissue, capillaries, and fat Rodak #76 Core Biopsy shows 50 % fat and 50 % hematopoietic tissue
Hematopoietic SystemBone Marrow • Amount of red marrow varies with age of patient • Childhood: Red marrow is 100% of BM and present in virtually every bone • Adults: Red marrow is ~50% of BM and present in sternum, ribs, pelvis, and skull • ~70 years: Red marrow reduced to ~ 30% of the BM
Slides • Slide -Changes in site for Hematopoiesis with age • Bone Marrow in Skeleton Rodak 4 • Bone Marrow Biopsy Site Rodak 66 • ASCP Bone Marrow 13: Cellular, 5 y.o • 14: Less Cellular 35 y.o. • 30: Hypocellular, aplastic anemia
Clinical Evaluation Tests of Bone Marrow Function Small amounts of myeloid tissue (myelos=marrow) is removed from bone cavity and examined under the microscope- Bone marrow aspiration Bone marrow biopsy
Hematopoietic SystemBone Marrow Bone Marrow Core Biopsy Cellularity and the architecture Bone Marrow Aspiration Cytology and maturation
Slides • Rodak 76: Core biopsy; Cellularity 50% • ASCP BM 237: AIDS granuloma • #204: Spindle cells • Robbins #338 Hypoplastic • Pathology 13.26 Hyperplastic • Pathology 13.27 Hyperplastic due to acute leukemia
Slides • Bone Marrow Aspiration • Rodak 67 Aspirate smear • Rodak # 68 Myeloblast, promyelocyte, myelocyte, and lymphocyte • Rodak #71 Bands and segs
Hematopoiesis Key Terms • Stem cells • Precursors cells (Blasts) • Terms for each stage in the morphologic differentiation
Proerythroblast Basophilic erythroblast Polychromatophilic erythroblast Orthrochromatophic erythroblast Reticulocyte Erythrocyte Myeloblast Promyelocyte Myelocyte Metamyelocyte Band cell Mature granulocyte (neutrophil, eosinophil, or basophil) Hematopoiesis
Slides • RBC Maturation • Harmening1-3 • Histology 6.5 • ASCP 2.6 • 2.9 • 2.7 • 2.10
Slides • 2.12 • 2.14 • 2.15 • CAP Polychromasia • CAP Reticulocyte stain
Medical HistologyRBC Maturation Sequence The red cell maturation sequence and significance of the change in red cell size and cytoplasmic color • Polychromatophilic red blood cells to illustrate newly released red cells • Reticulocytes to illustrate bone marrow response to anemia • Nucleated red blood cells in peripheral blood to illustrated bone marrow stress
Slides • Diagram of red cell maturation and time sequence • Normal; red blood cells • CAP Polychromasia • CAP Reticulocyte stain
Slides • ASCP 4-30 Polychromatophilic RBC with basophilic • ASCP 2-17 Reticulocyte stained with methylene blue • ASCP 2-18 Normal mature RBC • ASCP4-33 and 34 RBC and Rete stain • CAP: Nucleated red blood cell
Medical Histology Erythropoiesis Recognize the bone marrow response to anemia • Accelerated Erythropoiesis • Released Reticulocytes • Insufficient Erythropoiesis • Inadequate reticulocytes
Medical Histology Bone Marrow and Red Cell Size • Recognize the clinical significance of size of red cells • Recognize the size change with maturation • Classify anemia based on red cell size • Small = Microcytic • Large = Macrocytic • Normal = Normocytic
Slides • Histology Figure 6-5 Stages • ASCP 2-06 Pronormoblast and orthroblast • ASCP 2-12 Orthro and polychrom • ASCP 2-15 Poly, orthro, polychromatophilic RBC • ASCP 2-14 Orthro losing its nucleus, late poly
Slides • Rodak # 86 Iron Deficiency • ASCP 4-16 Iron Deficiency • ASCP 4- 20 Macrocytic with Lymphocyte
Proerythroblast Basophilic erythroblast Polychromatophilic erythroblast Orthrochromatophic erythroblast Reticulocyte Erythrocyte Myeloblast Promyelocyte Myelocyte Metamyelocyte Band cell Mature granulocyte (neutrophil, eosinophil, or basophil) Hematopoiesis
Slides • Histology 6.8 all stages • Harmening 1-17: Blast, promyelocyte, myelocyte, metamyelocyte, band, segmented; eosinophil myelocyte, metamyelocyte, band, and mature eosinophil • ASCP 2-22: Myeloblast and promyelocyte • ASCP 2-25 Promyelocyte, myelocyte, band, segmented neutrophil
Medical HistologyNeutrophilia and Immature Cells • Leukocyte Maturation and Response to Infection produces a left shifted maturation: early cells in the peripheral blood • Increased numbers of neutrophils leave the bone marrow storage spaces • Increased neutrophil production • Immature forms - bands, metamyelocytes, and even myelocytes leave the bone marrow
Slides • Leukocytosis with left Shift
Medical HistologyLeukocyte Maturation Leukemia and Maturation of Leukocytosis • Acute Leukemia: Immature cells • Granulocyte maturation AML • Lymphocyte maturation ALL • Chronic Leukemia: Mature cells • Granulocyte maturation CML • Lymphocyte maturation CLL
Slides • Saunders # 349 Lack of maturation, monotonous population, acute leukemia • CAP HE-23 Mature lymphocyte and lymphoblast • ASCP 6-10 Maturation of granulocytic cells in CGL
Slides • Cancer 13.18 Maturation of granulocytic cells • ASCP 6-40 Maturation of granulocytic cells • ASCP 6-45 and 6-46 CLL monotonous population • CAP HE-25 Normal lymphocyte • Saunders #353 CLL
Platelet Maturation • Platelet fragmentation from megakaryocytes; these differentiated from megakaryoblasts
Slides • ASCP 2-49 Megakaryocyte Identification • ASCP 2-52 Active (Platelet forming) Bone Marrow Megakaryocytes • ASCP 2-53 Platelets in bone marrow last of the platelets released; nucleus remains
Medical HistologyThrombocytopenia • Increased Destruction and Utilization • Impaired Production
Slides • ASCP BM: • Rodak 208 BM Aspirate with numerous megakaryocytes , but few or no platelets seen in the peripheral blood
Hematopoiesis • Monocyte maturation from monoblast • Lymphocytes
Question A 54 year old man has a neoplastic disorder that shows a peripheral blood leukocytosis with a predominance of mature neutrophils, few myelocytes, metamyelocytes, and promyelocytes. Myeloblasts are not identified What is the most likely diagnosis? • Acute leukemia • Chronic leukemia • Lymphoma
Question Peripheral blood smear. Identify this cell • Nucleated red blood cell • Polychromatophilic red blood cell • Reticulocyte • Polymorphonuclear neutrophil • Eosinophil
Question This basophilic staining large cell is present in the peripheral blood of a patient appropriately treated for anemia. What is the most like cause for this coloration? • Iron granules • Neoplastic primary granules • Residual DNA • Residual RNA
Question Which of the following hematologic evaluations is most likely to give useful information about the maturation and cytology of the erythroid and granulocytic series? • Bone marrow aspiration • Bone marrow core biopsy • Complete blood cell count