Hematopoietic System- 1Hematopoietic System- 1Bone Marrow HematopoiesisBone Marrow Hematopoiesis

Linda F. Cunningham, MDLinda F. Cunningham, MD

January 2, 2003January 2, 2003

Hematopoietic SystemHematopoietic SystemBone MarrowBone Marrow

• Hematopoietic active marrow with stem Hematopoietic active marrow with stem cells, progenitor cells, and developing cells, progenitor cells, and developing erythroblasts, myeloblasts, and erythroblasts, myeloblasts, and megakaryoblasts (red marrow)megakaryoblasts (red marrow)

• Adipose cells, various with age and Adipose cells, various with age and activity (yellow marrow)activity (yellow marrow)

• Marrow sinuses and capillary networkMarrow sinuses and capillary network

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• ASCP Bone Marrow 3:ASCP Bone Marrow 3:

• Histology 6.2: Trabecular bone with Histology 6.2: Trabecular bone with hematopoietic tissue and fathematopoietic tissue and fat

• Rodak 7 Bone Marrow with Rodak 7 Bone Marrow with hematopoietic tissue, capillaries, and fathematopoietic tissue, capillaries, and fat

Rodak #76 Core Biopsy shows 50 % fat Rodak #76 Core Biopsy shows 50 % fat and 50 % hematopoietic tissueand 50 % hematopoietic tissue

Hematopoietic SystemHematopoietic SystemBone Marrow Bone Marrow

• Amount of red marrow varies with age of Amount of red marrow varies with age of patientpatient– Childhood: Red marrow is 100% of BM and Childhood: Red marrow is 100% of BM and

present in virtually every bonepresent in virtually every bone– Adults: Red marrow is ~50% of BM and Adults: Red marrow is ~50% of BM and

present in sternum, ribs, pelvis, and skullpresent in sternum, ribs, pelvis, and skull– ~70 years: Red marrow reduced to ~ 30% of ~70 years: Red marrow reduced to ~ 30% of

the BMthe BM

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• Slide -Changes in site for Hematopoiesis Slide -Changes in site for Hematopoiesis with agewith age

• Bone Marrow in Skeleton Rodak 4Bone Marrow in Skeleton Rodak 4

• Bone Marrow Biopsy Site Rodak 66Bone Marrow Biopsy Site Rodak 66

• ASCP Bone Marrow 13: Cellular, 5 y.oASCP Bone Marrow 13: Cellular, 5 y.o

• 14: Less Cellular 35 y.o.14: Less Cellular 35 y.o.

• 30: Hypocellular, aplastic anemia30: Hypocellular, aplastic anemia

Clinical Evaluation Clinical Evaluation Tests of Bone Marrow Function Tests of Bone Marrow Function

Small amounts of myeloid tissue Small amounts of myeloid tissue ((myelosmyelos=marrow) is removed from bone =marrow) is removed from bone cavity and examined under the cavity and examined under the microscope-microscope-

Bone marrow aspirationBone marrow aspiration

Bone marrow biopsyBone marrow biopsy

Hematopoietic SystemHematopoietic SystemBone MarrowBone Marrow

Bone Marrow Core BiopsyBone Marrow Core Biopsy

Cellularity and the architectureCellularity and the architecture

Bone Marrow AspirationBone Marrow Aspiration

Cytology and maturationCytology and maturation

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• Rodak 76: Core biopsy; Cellularity 50%Rodak 76: Core biopsy; Cellularity 50%

• ASCP BM 237: AIDS granulomaASCP BM 237: AIDS granuloma

• #204: Spindle cells#204: Spindle cells

• Robbins #338 HypoplasticRobbins #338 Hypoplastic

• Pathology 13.26 Hyperplastic Pathology 13.26 Hyperplastic

• Pathology 13.27 Hyperplastic due to Pathology 13.27 Hyperplastic due to acute leukemia acute leukemia

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• Bone Marrow AspirationBone Marrow Aspiration– Rodak 67 Aspirate smearRodak 67 Aspirate smear– Rodak # 68 Myeloblast, promyelocyte, Rodak # 68 Myeloblast, promyelocyte,

myelocyte, and lymphocyte myelocyte, and lymphocyte – Rodak #71 Bands and segs Rodak #71 Bands and segs

HematopoiesisHematopoiesis

Key TermsKey Terms

• Stem cellsStem cells

• Precursors cells (Blasts) Precursors cells (Blasts)

• Terms for each stage in the morphologic Terms for each stage in the morphologic differentiationdifferentiation

HematopoiesisHematopoiesis

• ProerythroblastProerythroblast• Basophilic Basophilic

erythroblasterythroblast• Polychromatophilic Polychromatophilic

erythroblasterythroblast• Orthrochromatophic Orthrochromatophic

erythroblasterythroblast• ReticulocyteReticulocyte• ErythrocyteErythrocyte

• MyeloblastMyeloblast• PromyelocytePromyelocyte• MyelocyteMyelocyte• MetamyelocyteMetamyelocyte• Band cellBand cell• Mature granulocyte Mature granulocyte

(neutrophil, (neutrophil, eosinophil, or eosinophil, or basophil)basophil)

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• RBC MaturationRBC Maturation

• Harmening1-3Harmening1-3

• Histology 6.5Histology 6.5

• ASCP 2.6ASCP 2.6

• 2.92.9

• 2.72.7

• 2.102.10

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• 2.122.12

• 2.142.14

• 2.152.15

• CAP PolychromasiaCAP Polychromasia

• CAP Reticulocyte stainCAP Reticulocyte stain

Medical HistologyMedical HistologyRBC Maturation Sequence RBC Maturation Sequence

The The red cell maturation sequencered cell maturation sequence and and significance of the change in red cell size significance of the change in red cell size and cytoplasmic colorand cytoplasmic color– Polychromatophilic red blood cellsPolychromatophilic red blood cells to to

illustrate newly released red cells illustrate newly released red cells – ReticulocytesReticulocytes to illustrate bone marrow to illustrate bone marrow

response to anemiaresponse to anemia– Nucleated red blood cellsNucleated red blood cells in peripheral blood in peripheral blood

to illustrated bone marrow stressto illustrated bone marrow stress

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• Diagram of red cell maturation and time Diagram of red cell maturation and time sequencesequence

• Normal; red blood cellsNormal; red blood cells

• CAP PolychromasiaCAP Polychromasia

• CAP Reticulocyte stainCAP Reticulocyte stain

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• ASCP 4-30 Polychromatophilic RBC ASCP 4-30 Polychromatophilic RBC with basophilic with basophilic

• ASCP 2-17 Reticulocyte stained with ASCP 2-17 Reticulocyte stained with methylene bluemethylene blue

• ASCP 2-18 Normal mature RBCASCP 2-18 Normal mature RBC

• ASCP4-33 and 34 RBC and Rete stainASCP4-33 and 34 RBC and Rete stain

• CAP: Nucleated red blood cellCAP: Nucleated red blood cell

Medical Histology Medical Histology ErythropoiesisErythropoiesis

Recognize the bone marrow response to Recognize the bone marrow response to anemiaanemia

• Accelerated ErythropoiesisAccelerated Erythropoiesis– Released ReticulocytesReleased Reticulocytes

• Insufficient Erythropoiesis Insufficient Erythropoiesis – Inadequate reticulocytesInadequate reticulocytes

Medical Histology Medical Histology Bone Marrow and Red Cell SizeBone Marrow and Red Cell Size

• Recognize the clinical significance of size Recognize the clinical significance of size of red cellsof red cells

• Recognize the size change with Recognize the size change with maturationmaturation

• Classify anemia based on red cell sizeClassify anemia based on red cell size– Small = MicrocyticSmall = Microcytic– Large = MacrocyticLarge = Macrocytic– Normal = NormocyticNormal = Normocytic

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• Histology Figure 6-5 StagesHistology Figure 6-5 Stages• ASCP 2-06 Pronormoblast and ASCP 2-06 Pronormoblast and

orthroblastorthroblast• ASCP 2-12 Orthro and polychromASCP 2-12 Orthro and polychrom• ASCP 2-15 Poly, orthro, ASCP 2-15 Poly, orthro,

polychromatophilic RBCpolychromatophilic RBC• ASCP 2-14 Orthro losing its nucleus, late ASCP 2-14 Orthro losing its nucleus, late

poly poly

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• Rodak # 86 Iron Deficiency Rodak # 86 Iron Deficiency • ASCP 4-16 Iron DeficiencyASCP 4-16 Iron Deficiency• ASCP 4- 20 Macrocytic with LymphocyteASCP 4- 20 Macrocytic with Lymphocyte

•

HematopoiesisHematopoiesis

• ProerythroblastProerythroblast• Basophilic Basophilic

erythroblasterythroblast• Polychromatophilic Polychromatophilic

erythroblasterythroblast• Orthrochromatophic Orthrochromatophic

erythroblasterythroblast• ReticulocyteReticulocyte• ErythrocyteErythrocyte

• MyeloblastMyeloblast• PromyelocytePromyelocyte• MyelocyteMyelocyte• MetamyelocyteMetamyelocyte• Band cellBand cell• Mature granulocyte Mature granulocyte

(neutrophil, (neutrophil, eosinophil, or eosinophil, or basophil)basophil)

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• Histology 6.8 all stagesHistology 6.8 all stages• Harmening 1-17: Blast, promyelocyte, Harmening 1-17: Blast, promyelocyte,

myelocyte, metamyelocyte, band, segmented; myelocyte, metamyelocyte, band, segmented; eosinophil myelocyte, metamyelocyte, band, eosinophil myelocyte, metamyelocyte, band, and mature eosinophiland mature eosinophil

• ASCP 2-22: Myeloblast and promyelocyteASCP 2-22: Myeloblast and promyelocyte• ASCP 2-25 Promyelocyte, myelocyte, band, ASCP 2-25 Promyelocyte, myelocyte, band,

segmented neutrophilsegmented neutrophil

Medical HistologyMedical HistologyNeutrophilia and Immature CellsNeutrophilia and Immature Cells

• Leukocyte Maturation and Response to Leukocyte Maturation and Response to Infection produces a left shifted Infection produces a left shifted maturation: early cells in the peripheral maturation: early cells in the peripheral bloodblood– Increased numbers of neutrophils leave the Increased numbers of neutrophils leave the

bone marrow storage spaces bone marrow storage spaces – Increased neutrophil productionIncreased neutrophil production– Immature forms - bands, metamyelocytes, Immature forms - bands, metamyelocytes,

and even myelocytes leave the bone marrow and even myelocytes leave the bone marrow

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• Leukocytosis with left ShiftLeukocytosis with left Shift

Medical HistologyMedical HistologyLeukocyte MaturationLeukocyte Maturation

Leukemia and Maturation of LeukocytosisLeukemia and Maturation of Leukocytosis

– Acute Leukemia: Immature cellsAcute Leukemia: Immature cells• Granulocyte maturation AMLGranulocyte maturation AML

• Lymphocyte maturation ALLLymphocyte maturation ALL

– Chronic Leukemia: Mature cellsChronic Leukemia: Mature cells• Granulocyte maturation CMLGranulocyte maturation CML

• Lymphocyte maturation CLLLymphocyte maturation CLL

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• Saunders # 349 Lack of maturation, Saunders # 349 Lack of maturation, monotonous population, acute leukemiamonotonous population, acute leukemia

• CAP HE-23 Mature lymphocyte and CAP HE-23 Mature lymphocyte and lymphoblastlymphoblast

• ASCP 6-10 Maturation of granulocytic ASCP 6-10 Maturation of granulocytic cells in CGLcells in CGL

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• Cancer 13.18 Maturation of granulocytic Cancer 13.18 Maturation of granulocytic cellscells

• ASCP 6-40 Maturation of granulocytic ASCP 6-40 Maturation of granulocytic cellscells

• ASCP 6-45 and 6-46 CLL monotonous ASCP 6-45 and 6-46 CLL monotonous populationpopulation

• CAP HE-25 Normal lymphocyteCAP HE-25 Normal lymphocyte• Saunders #353 CLLSaunders #353 CLL

Platelet MaturationPlatelet Maturation

• Platelet fragmentation from Platelet fragmentation from megakaryocytes; these differentiated megakaryocytes; these differentiated from megakaryoblastsfrom megakaryoblasts

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• ASCP 2-49 Megakaryocyte IdentificationASCP 2-49 Megakaryocyte Identification

• ASCP 2-52 Active (Platelet forming) ASCP 2-52 Active (Platelet forming) Bone Marrow Megakaryocytes Bone Marrow Megakaryocytes

• ASCP 2-53 Platelets in bone marrow last ASCP 2-53 Platelets in bone marrow last of the platelets released; nucleus remainsof the platelets released; nucleus remains

Medical HistologyMedical HistologyThrombocytopeniaThrombocytopenia

• Increased Destruction and UtilizationIncreased Destruction and Utilization

• Impaired ProductionImpaired Production

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• ASCP BM: ASCP BM:

• Rodak 208 BM Aspirate with numerous Rodak 208 BM Aspirate with numerous megakaryocytes , but few or no platelets megakaryocytes , but few or no platelets seen in the peripheral bloodseen in the peripheral blood

HematopoiesisHematopoiesis

• Monocyte maturation from monoblastMonocyte maturation from monoblast

• LymphocytesLymphocytes

QuestionQuestion

A 54 year old man has a neoplastic disorder A 54 year old man has a neoplastic disorder that shows a peripheral blood that shows a peripheral blood leukocytosis with a predominance of leukocytosis with a predominance of mature neutrophils, few myelocytes, mature neutrophils, few myelocytes, metamyelocytes, and promyelocytes. metamyelocytes, and promyelocytes. Myeloblasts are not identified What is Myeloblasts are not identified What is the most likely diagnosis? the most likely diagnosis?

A.A. Acute leukemiaAcute leukemiaB.B. Chronic leukemiaChronic leukemiaC.C. LymphomaLymphoma

QuestionQuestion

Peripheral blood smear. Identify this cellPeripheral blood smear. Identify this cell

A.A. Nucleated red blood cellNucleated red blood cell

B.B. Polychromatophilic red blood cellPolychromatophilic red blood cell

C.C. ReticulocyteReticulocyte

D.D. Polymorphonuclear neutrophilPolymorphonuclear neutrophil

E.E. EosinophilEosinophil

QuestionQuestion

This basophilic staining large cell is This basophilic staining large cell is present in the peripheral blood of a present in the peripheral blood of a patient appropriately treated for patient appropriately treated for anemia. What is the most like cause for anemia. What is the most like cause for this coloration?this coloration?

A.A. Iron granulesIron granulesB.B. Neoplastic primary granulesNeoplastic primary granulesC.C. Residual DNAResidual DNAD.D. Residual RNAResidual RNA

QuestionQuestion

Which of the following hematologic Which of the following hematologic evaluations is most likely to give useful evaluations is most likely to give useful information about the maturation and information about the maturation and cytology of the erythroid and cytology of the erythroid and granulocytic series?granulocytic series?

A.A. Bone marrow aspirationBone marrow aspirationB.B. Bone marrow core biopsyBone marrow core biopsyC.C. Complete blood cell count Complete blood cell count