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) 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 System Bone 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 System Bone 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

Hematopoiesis Myeloblast Proerythroblast Promyelocyte Metamyelocyte Band cell Mature granulocyte (neutrophil, eosinophil, or basophil) Proerythroblast Basophilic erythroblast Polychromatophilic erythroblast Orthrochromatophic erythroblast Reticulocyte Erythrocyte

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 Histology RBC 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

Hematopoiesis Myeloblast Proerythroblast Promyelocyte Metamyelocyte Band cell Mature granulocyte (neutrophil, eosinophil, or basophil) Proerythroblast Basophilic erythroblast Polychromatophilic erythroblast Orthrochromatophic erythroblast Reticulocyte Erythrocyte

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 Histology Neutrophilia 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 Histology Leukocyte 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 Histology Thrombocytopenia 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