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OBJECTIVES
1.) Define Hematopoiesis
2.) Discuss the anatomy and function of the bone marrow
3.) Describe:a.) Erythropoiesis
b.) Granulopoiesis
c.) Thrombopoiesis
d.) Lymphopoiesis
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Basic Facts about the Blood
Ave. Total Volume
Male: 5 L
Female: 4 L
Composition: Plasma (55%)
50% water
5-7% plasma proteins
(albumin, globulin,
fibrinogen)
Cellular elements (45%)
RBCs, WBCs, platelets
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Describes the origin of and process by which new mature
blood cells are produced
Occurs because blood cells have relatively short lifespan
Blood Cell Lifespan
RBC 120 days
Platelet 9-12 days
WBC
Neutrophils 6-7 hours to 1-4 daysEosinophils approx. 8 hours
Basophils ?
Lymphocytes Variable (days to years)
Continuously recirculating
Monocytes 1-3 days to months or years
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Embryonic Life
•Yolk Sac
•Liver
•Spleen
•Bone marrow
Adult
•Bone marrow
•Liver *
•
Spleen *
* extramedullary sitesof hematopoiesis
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Yellow Marrow
Inactive in hematopoiesis
Consists of adipose tissue
that give it its color Red Marrow
Active in hematopoiesis
Highly cellular
Hematopoietic
Compartment
Hematopoietic cords
Reticular cells & fibers Fat deposits
Macrophages,
megakaryocytes
Vascular Compartment Nutrient Arteries
Venous Sinusoids
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Hematopoietic cells proliferate and differentiate in the
interstices of stroma between the sinusoidal vessels
Preferential localization of blood cells
Erythroid series – form islands with macrophage in the center
Megakaryocyte – near sinusoids
Granulocyte series – intervascular spaces
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Hematopoiesis
Myelopoiesis
Erythropoiesis
Erythrocytes
Granulopoiesis
Monocyte
Neutrophil
Eosinophils *
Basophils *
Mast Cells **
Thrombopoiesis
Platelets
Lymphopoiesis
NK Cells
T-lymphocytes
B-lymphocytes
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Hematopoietic Stem Cells
0.5% of all bone marrow nucleated cells
Not morphologically distinguishable
Committed Progenitor Cells Aka CFUs and/or BFUs
Approx. 3% of total bone marrow nucleated cells
Survival and differentiation are influenced by growth regulatory
glycoproteins (cytokines) Negative regulators: interferons, prostaglandins, T-suppressor
cells
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Erythropoietin (EPO)
Kidney, liver
Hypoxia Decreased blood volume
Anemia Decreased Hgb
Decreased blood flow to tissues
Pulmonary disease
Activates blast forming units to differentiate into
proerythroblast Increase rate of mitosis and maturation process
Increase rate of Hgb production
Increase rate of reticulocyte release into peripheral blood
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Decreasing cell size
Pyknotic nucleus
Loss of cytoplasmic organelles
basophilic cytoplasm (due to ribosomes) to eosinophilic
cytoplasm (due to hemoglobin)
Vitamin B12 and folic acid
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Proerythroblast / Pronormoblast
Basophilic (Early) Erythroblast
Polychromatophilic (intermediate/late) Erythroblast
Orthochromic erythroblast / Normoblast
Reticulocyte
Mature RBC
• 3-5 mitotic divisions: proerythroblast topolychromatophilicerythroblast
• maturation = 2-7 days:proerythroblast toorthochromic erythroblast
• 1 day to extrude nucleusfrom orthochromatophilic
erythroblast• Reticulocyte matures 2-3
days in the marrow beforeits release into blood
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Proerythroblast Basophilic Erythroblast
14-20μm
First histologically
identifiable cell in the series Nucleus: large, slightly oval,
reddish, with loose lacychromatin, clearly visiblenucleoli (1-3)
Deeply basophilic cytoplasm
N:C ratio = 8:1
1% of nucleated cells in thebone marrow
10-16μm
Strongly basophiliccytoplasm due to abundantribosomes for the synthesisof Hgb
Cells is smaller than
proerythroblast Nucleus is darker with
coarser chromatin
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Polychromatophilic
erythroblast Normoblast
10-12μm
Amount of ribosomes
decreases as hemoglobin fillthe cytoplasm
Nucleas with checker boardappearance formed by coarsechromatin granules
Cytoplasm is grayish in color mixture of basophilia due to
ribosomes and eosinophiliadue to Hgb
Aka Orthochromic erythroblast
8-10μm
Nuclues continues to condense(pyknotic and eccentric)
N:C ratio = 1:2
More eosinophilic cytoplasmbec. hemoglobin completely fillsup the cell
1-4% of nucleated cells in thebone marrow
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Reticulocyte Mature erythrocyte
7-10μm
Pink to pinkish gray cytoplasm
No nucleus
Few ribosomes
Immature RBC released into thecirculation
Cannot be distinguished frommature RBC using routine stains
Amount is increased inconditions of increased RBCproduction
7-9μm (~7.5μm)
Pink cytoplasm No nucleus
Biconcave shape
Ave. Vol = 90-95 cubicμm
Ave no:
5.2 M Males
4.7 M Females
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Development from stem
cells to mature
granulocytes is about 18
days
* During the myeloblast
and promyeloblast stage,
neutrophilic, eosinophilic
and basophilic lineages
cannot be distinguished
Myeloblast
Promyelocyte
Early
Basophilicmyelocyte
Early
Eosinophilicmyelocyte
Early
Neutrophilicmyelocyte
Late
Basophilic
myelocyte
Late
Eosinophilic
myelocyte
Late
Neutrophilic
myelocyte
BasophilicMetamyelocyte
EosinophilicMetamyelocyte
NeutrophilicMetamyelocyte
Band Cell
Mature
Neutrophil
Mature
Eosinophil
Mature
Basophil
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Myeloblast Promyelocyte
Most immature cell in theseries
15-20μm
Oval nucleus with finelydispersed chromatin
Basophilic cytoplasm (pale
blue-gray)
No specific granules
3 or more nucleoli
Largest cell in the series(~17-26μm)
Bluish cytoplasm withnumerous azurophilicgranules
Reddish blue rounded
nucleus, chromatin morecoarse than myeloblast
Nucleolust present
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Myelocyte Metamyelocyte
Pale cytoplasm
Round to flattened nucleus
Nucleoli not distinct
Clear perinuclear golgiregion evident
Specific granules present (3types of myelocytes)
Neutrophilic myelocyte
Eosinophilic myelocyte
Basophilic myelocyte
Paler color of cytoplasm
compared to myelocyte
Kidney-shaped nucleus
No nucleoli
Golgi area nestled in the
indentation of the nucleus
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Metamyelocyte
Neutrophilic metamyelocyte Nucleus becomes increasingly lobulated
Band stage is required because of highly lobulated nucleus
Eosinophilic metamyelocyte Distinguished from neutrophilic metamyelocyte by the larger size and
eosinophilic staining of cytoplasmic granules
Nuecleus is indented but not as lobulated as neutrophilicmetamyelocytes
Basophilic metamyelocytes Rarely observed because of their small numbers and the difficulty in
preserving their granules
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Neutrophilic Band Cell * Mature Granulocyte
Aka Stab cell
Have only entered the
circulation Cytoplasm is bluer compared to
neutrophil
Nucleus is more condensed andindented
Horse-shoe shaped nucleus withcoarse chromatin
Increase in number suggestsincreased response to infection
Either:
Eosinophil Basophil
Neutrophil
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Mature Granulocytes
Mature Neutrophils Long nucleus is narrowed at several places resulting in distinct nuclear lobules Barr body (aka drumstick chromosome) may be present - condensation of the X-
chromosome (from sample of female patients)
Mature Eosinophils Nucleus never attains the degree of lobulation seen in neutrophils (2 lobed
connected by a broad intermediate segment)
Large pink coarse granules
Mature Basophils Nucleus is deeply indented or lobulated (but this will not be very distinct)
Cytoplasm contains large, intensely basophilic granules
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LymphoblastLymphocyte progenitor cell
Lymphoblast
Prolymphocyte
Lymphocyte
Scant to moderate
cytoplasm
Dispersed chromatin
Variably prominent
nucleoli
NB: You cannot distinguish T-lymphocytes from B-lymphocytes using regular staining and light microscopy. (Immunohistochemistry techniques)
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Prolymphoblast Lymphocytes
Nuclei with deeply staining
condensed chromatin
Small basophilic cytoplasm
with few organelles
Some remain in the bone
marrow and dividethroughout life producing
lymphocytes
8 – 10μm
Round, oval nucleus
High nuclear: cytoplasmicratio (large nucleus withrim of cytoplasm)
Variably prominent
nucleoli
Densely clumpedchromatin
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CFU – MMonoblast PromonocyteMonocyte
Changes that occur during monopoiesis Cell becomes smaller
Nucleus: spherical kidney shaped
Fine azurophilic granules appear
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MegakaryoblastMegakaryocyte Platelets
Changes that occur during megakaryopoiesis: Cells become bigger
Nucleus become bigger and multilobed
Cytoplasmic granules increase
Increased membranes Cytoplasm becomes less basophilic
A single megakaryocyte may be able to release 8000 platelets
before it degenerates and is replaced
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Megakaryoblast Megakaryocyte
Smaller than
megakaryocyte
30-45μm
Bilobed nucleus
More basophilic
cytoplasm
Largest and most easily recognizable
cell in the bone marrow
35 - 150μm
Multilobed nucleus
In the late stage of the
megakaryocyte, granules clusterand are eventually partitioned into
fragments
Platelet demarcation membrane