HIS-1

Hematopoeitic
System

Alya Amila Fitrie

Lokot Donna Lubis

Department of Histology
Faculty of Medicine
University of Sumatera Utara
Medan 2015
BLOOD CELLS

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 HEMATOPOIEISIS IN THE FETUS

• In the adult, an approximate volume of 1.7 L of marrow

contains 10 12 hematopoietic cells.
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STEM CELLS, GROWTH FACTORS &
DIFFERENTIATION
 Hematopoietic
Stem Cells
(HSCs)

Di
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if

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Specific,
Remain irreversibly
stem cells differentiated cell
types
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2 PROCESSES INVOLVED IN FORMATION OF
BLOOD CELLS: (addition)
1. Differentiation:
– The progressive acquisition of the biochemical,
functional, & morphologic characteristics of the
particular cell type
– Occurs at all stages of hematopoiesis

2. Cell proliferation:
– The production of a large number of mature cells from
a single cell committed to one or more differentiation
pathways
– Occurs in the hematopoietic stem cells, progenitor
cells, (except in the megakaryocytic lineage) & in the
precursor cells
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PLURIPOTENTIAL HEMATOPOIETIC
STEM CELLS
Migrate from the bone marrow to the lymphoid organ,
where they proliferate : lymphocytes

Lymphoid cell

All blood cells arise from a single type of stem cell

in the bone marrow  pluripotential
hematopoietic stem cells
(HSCs)

Myeloid cell
Develop in bone marrow : granulocytes, monocytes,
erythrocytes & megakaryocytes
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PRECURSOR CELL LINEAGE

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Hematopoietic Progenitor Cells or Colony-forming
Units (Cfus) (addition)
• Hematopoietic Progenitor Cells or
Colony-forming Units (Cfus) or
Colony Forming Cells (CFC)
characterized by their ability to
form colonies containing cells of
one or more hematopoietic
lineages → multipotent, tripotent,
bipotent or unipotent
• CFU-GEMM: generate colonies
containing a mixture of
granulocytes, erythroblasts,
macrophages, & megakaryocytes
• Tripotent hematopoietic
progenitor cells → CFU-E mega
baso generate erythroblasts,
megakaryocytes, &basophil
granulocytes
• Bipotent hematopoietic
progenitor cells
– CFU-GM generate colonies
containing granulocytes &
macrophages
– CFU-E mega generating colonies
containing a mixture of
erythroblasts & megakaryocytes
• The unipotent progenitor cells:
– CFUG generate neutrophil
granulocytes
– CFU-eo generate eosinophil
granulocytes,
– CFU-baso generate basophil
granulocytes,
– CFU-M generate macrophages
– CFU-E generate erythroblasts
– CFU-mega generate
megakaryocytes 10
RATE OF DIVISION HEMATOPOIETIC CELLS (addition)
• Stem cells divide at a rate only sufficient to maintain their
relatively small population.

• Accelerated cell division rate in progenitor & precursor

cells:
– Progenitor cells divide asymmetrically to produce both progenitor
& precursor cells
– Precursor cells produce only cells on the path to differentiation

• Daily production of differentiated, mature cells in human

bone marrow :
– 3 x 109 erythrocytes/kg/day
– 0.85 x 109 granulocytes/kg/day
– in human bone marrow). Whereas.

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DIFFERENTIATION OF PLURIPOTENTIAL CELLS
DURING HEMATOPOEISIS

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HEMATOPOIETIC GROWTH FACTORS
• Def : Glicoprotein produced in the bone
marrow by endothelial cells, stromal cells,
fibroblast, developing lymphocytes &
macrophage

• Also produced outside the bone marrow

• Act mainly by :
1. Stimulating proliferation of immature cells
2. Supporting the differentiation of maturing cells
3. Extending the life span and enhancing the functions
of mature cells.
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3 MAJOR GROUPS OF HEMATOPOIETIC
GROWTH FACTORS

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HEMATOPOEITIC GROWTH FACTORS

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 BONE MARROW
• A large & complex organ →
Found in medullary canals of long
bones & in cavities of cancellous
bone

• Two types of bone marrow :

1. Red or hematogenous bone
marrow  blood & blood-
forming cells
2. Yellow bone marrow 
adipose cells

• All newborn  red b.m

• Growth : red  yellow b.m. 17

 BONE MARROW (addition)
• Total mass of an adult: • The hematopoietic marrow: (labile
1600 to 3700 g (50% & altering rapidly in response to
fatty marrow:50% many stimuli)
hematopoietically 1. Hematopoiesis (formation & release of
active marrow) various blood cells), mast cells,
osteoclasts, & some endothelial
progenitor cells
• The function of bone 2. Phagocytosis & degradation of
marrow: circulating particulate material such as
– microorganisms & abnormal or
Hematopoiesis site senescent red cells and leukocytes
(hematopoietic
marrow) 3. Antibody production
– Mesenchymal stem
cells source that can • Marrow mesenchymal stem cells →
differentiate into
other type of cells differentiate into adipocytes,
– A large store of hepatocytes, osteoblasts &
reserve lipid (fatty osteocytes, chondrocytes, skeletal &
marrow ) cardiac muscle cells, kidney cells &
neural cell lineages
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The Stroma of Bone Marrow (addition)
• Red bone marrow composed of:
– Stroma (Gr: stroma, bed)
– Hemopoietic cords or islands of cells
– Sinusoidal capillaries

• The stroma consist of:

– A meshwork of specialized fibroblastic cells called reticular or
adventitial cells
– A delicate web of reticular fibers supporting hemopoietic cells &
macrophages

• The matrix of bone marrow also contains collagen type I,

proteoglycans, fibronectin, and laminin, the latter
glycoproteins interacting with integrins to bind cells to the
matrix.
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2 COMPARTMENTS OF BONE MARROW:

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THE MARROW STROMAL COMPARTMENT

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THE HEMATOPOIETIC CELL COMPARTMENT

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Red Bone Marrow

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Bone Marrow

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THE PASSAGE OF BLOOD CELLS ACROSS A SINUSOID
CAPILLARY IN RED BONE MARROW

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STRUCTURE OF BONE MARROW

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1. MATURATION OF ERYTHROCYTES
SUMMARY OF ERYTHROCYTE MATURATION

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 ERYTROPOIESIS
• The major regulator of erytropoiesis →
erytropoietin (EPO)

• Erytropoetin → a glicoprotein produced primarily

in the kidney in respon to hypoxia

• In addition to EPO, the formation of RBCs highly

dependent
– iron metabolism
– vitamin folic acid
– vitamin B12.
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2. GRANULOPOEISIS
 LEUKOPOIESIS : GRANULOCYTES
• The Granulocyte-Macrophage CFU: A common
precursor cell of Neutrophilic & macrophage cell
lines

• Eosinophil CFU form Eosinophil

• Basophil Cfus form basophil

• The granulocytes (NEUTROPHIL, EOSINOPHIL &

BASOPHIL) → Have a similar pattern of
proliferation, differentiation, maturation & storage
in the BM
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DIFFERENTIATION OF GRANULOCYTES

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GRANULOPOEISIS

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STAGES IN THE DEVELOPMENT OF ERYTROCYTES &
GRANULOCYTES

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 Developing erythrocytes and granulocytes in marrow.
Plastic section of red bone marrow showing mitotic figures (arrows), a plasma cell
(arrowhead), & fairly distinct regions of erythropoiesis and granulopoiesis.
Most immature granulocytes are in the myelocyte stage: their cytoplasm contains
large, dark-stained azurophilic granules and small, less darkly stained specific
granules. 38
X400. Giemsa
Section of red bone marrow with a group of erythropoeitic cells &
a group of neutrophilopoeitic cells 39
KINETICS OF NEUTROPHIL PRODUCTION

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3. MATURATION OF LYMPHOCYTES &
MONOCYTES
 LYMPHOCYTES
Lymphocytes
progenitor cells
migrate in the bone
marrow

Thymus  full In the bone marrow,

attributes of T lymphocytes differentiate
lymphocytes  B lymphocytes

migrate
T lymphocytes populate
spesific regions of Peripheral lymphoid
peripheral lymphoid organs, B lymphocytes
organs inhabit & multiply in their
own special compartments

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 Origin of the main types of
lymphocytes

•B lymphocytes & natural killer

lymphocytes formed in the bone
marrow & leave the bone marrow
already mature, to seed the
secondary lymphoid organs &
transit through the blood,
epithelia, & connective tissues

•Immature CD4– & CD8– T

lymphocyte precursors
transported by the blood
circulation from the bone marrow
to the thymus, where they
complete their maturation &
leave as either CD4+ or CD8+ cells

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 LEUKOPOIESIS : AGRANULOCYTES 
MONOCYTE
• Monocyte : derive from GM-CSU  neutrophil
& macrophage lineage.

• Under the influence of spesific CSF, each

precursors cells establish its own hierarchy.
– G-CSF : Granulocyte precursor cell from GM-CSU 
myeloblast pathway.
– GM-CSF : Monocyte precursor cell from GM-CSU 
monoblast pathway.
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MONOCYTES
Monocyte :  up to 18
m, basophilic
cytoplasm, large &
slightly indented
nucleus, nucleoli are
evident

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 Clinical Significance :
Colony Stimulating Factors

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Clinical Significance :
Interleukin

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4. ORIGIN OF PLATELETS
ORIGIN OF PLATELETS
 15-50 m, large ovoid nucleus, numerous
nucleoli, cytoplasm homogenous and basophilic

Differentiation

 35-150 m, irregularly lobulated nucleus,

coarse chromatine, no visible nucleoli

Fragmentation of the
cytoplasm of mature
megakaryocyte

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 MEGAKARYOCYTE

A megakaryocyte in a section of red bone marrow. One

nucleus. Granular cytoplasm 50
 Referensi

• Basic Histology, Text and Atlas, 12th

edition, Luis Carlos Junqueira & Jose
Carneiro
• Histology & Cell Biology,Kierszenbaum.
• Essentials of Human Histology, Second
Edition, William J.Krause, 1996.
• Color Atlas of Basic Histology, Second
Edition, Lange, Irwin Berman, 1998.
• Wheather’s Functional Histology, A
Text and Colour Atlas, Fifth Edition,
Barbara Young, et al., 2006

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52
Histology of Blood

dr. Alya Amila Fitrie, M.Kes, Sp.PA

dr. Lokot Donna Lubis

Department of Histology
Faculty of Medicine
University of Sumatera Utara
Medan 2013
BLOOD

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PLASMA

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CELLULAR ELEMENTS

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ERYTHROCYTE / RED BLOOD CELLS (RBCS)

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CELL MEMBRANE OF A RBC

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RBCs & RETICULOCYTES

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SPLENOMEGALY Enlargement
of Spleen
Principal
Causes
Thalasemia: Hypochromic, microcystic
eritrocytes, poikilocytosis, target cells
CLINICAL SIGNIFICANCE

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LEUKOCYTES / WHITE BLOOD CELLS

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 GRANULOCYTES

Multilobed nucleus,  12-15 m. Lifespan varies,

can be distinguished by their cytoplasmic granules

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NEUTROPHIL

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NEUTROPHIL

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EOSINOPHIL

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Eosinophil

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BASOPHIL

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Basophil

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 AGRANULOCYTES

Round or indented nucleus, contain only

lysosomal-type, primary granules.

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LYMPHOCYTE

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LYMPHOCYTE

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LYMPHOCYTE

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MONOCYTES

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PLATELET

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PLATELET

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SUMMARY

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Thank 80