RR. Hematopoiesis

8/7/2019 RR. Hematopoiesis

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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



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



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



Embryonic Life

•Yolk Sac

•Liver

•Spleen

•Bone marrow

Adult

•Bone marrow

•Liver *

•

Spleen *

* extramedullary sitesof hematopoiesis



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



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



Hematopoiesis

Myelopoiesis

Erythropoiesis

Erythrocytes

Granulopoiesis

Monocyte

Neutrophil

Eosinophils *

Basophils *

Mast Cells **

Thrombopoiesis

Platelets

Lymphopoiesis

NK Cells

T-lymphocytes

B-lymphocytes



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



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



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



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



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



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



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



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



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



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



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



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



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



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)



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



CFU – MMonoblast PromonocyteMonocyte

Changes that occur during monopoiesis Cell becomes smaller

Nucleus: spherical kidney shaped

Fine azurophilic granules appear



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



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

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RR. Hematopoiesis