1. Hematopoietic System- 1 Bone Marrow Hematopoiesis
Linda F. Cunningham, MD
January 2, 2003

2. 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

3. 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

4. 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

5. 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

6. 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

7. Hematopoietic System Bone Marrow
Bone Marrow Core Biopsy
Cellularity and the architecture
Bone Marrow Aspiration
Cytology and maturation

8. Slides Rodak 76: Core biopsy; Cellularity 50%
ASCP BM 237: AIDS granuloma
#204: Spindle cells
Robbins #338 Hypoplastic
Pathology Hyperplastic
Pathology Hyperplastic due to acute leukemia

9. Slides Bone Marrow Aspiration Rodak 67 Aspirate smear
Rodak # 68 Myeloblast, promyelocyte, myelocyte, and lymphocyte
Rodak #71 Bands and segs

10. Hematopoiesis Key Terms Stem cells Precursors cells (Blasts)
Terms for each stage in the morphologic differentiation

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

12. Slides
RBC Maturation
Harmening1-3
Histology 6.5
ASCP 2.6
2.9
2.7
2.10

13. Slides
2.12
2.14
2.15
CAP Polychromasia
CAP Reticulocyte stain

14. 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

15. Slides Diagram of red cell maturation and time sequence
Normal; red blood cells
CAP Polychromasia
CAP Reticulocyte stain

16. 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

17. Medical Histology Erythropoiesis
Recognize the bone marrow response to anemia
Accelerated Erythropoiesis
Released Reticulocytes
Insufficient Erythropoiesis
Inadequate reticulocytes

18. 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

19. 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

20. Slides Rodak # 86 Iron Deficiency ASCP 4-16 Iron Deficiency
ASCP Macrocytic with Lymphocyte

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

22. 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

23. 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

24. Slides
Leukocytosis with left Shift

25. 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

26. Slides
Saunders # 349 Lack of maturation, monotonous population, acute leukemia
CAP HE-23 Mature lymphocyte and lymphoblast
ASCP Maturation of granulocytic cells in CGL

27. Slides Cancer 13.18 Maturation of granulocytic cells
ASCP 6-40 Maturation of granulocytic cells
ASCP and 6-46 CLL monotonous population
CAP HE-25 Normal lymphocyte
Saunders #353 CLL

28. Platelet Maturation
Platelet fragmentation from megakaryocytes; these differentiated from megakaryoblasts

29. 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

30. Medical Histology Thrombocytopenia
Increased Destruction and Utilization
Impaired Production

31. Slides
ASCP BM:
Rodak 208 BM Aspirate with numerous megakaryocytes , but few or no platelets seen in the peripheral blood

32. Hematopoiesis
Monocyte maturation from monoblast
Lymphocytes

33. 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

34. Question Peripheral blood smear. Identify this cell
Nucleated red blood cell
Polychromatophilic red blood cell
Reticulocyte
Polymorphonuclear neutrophil
Eosinophil

35. 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

36. 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