Red Bone Marrow

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‫بسم هللا الرحمن الرحيم‬
MYELOID TISSUE
Myeloid Tissue

Bone marrow is found in the medullary canals of
long bones and in the cavities of cancellous
bones.

Two types of bone marrow have been described
based on their appearance on gross examination:
1.
Red, or hematogenous, bone marrow, whose
color is produced by the presence of blood and
blood-forming cells;
2.
Yellow bone marrow, whose color is produced
by the presence of a great number of adipose
cells.
Myeloid Tissue

In newborns, all bone marrow is red and is
therefore active in the production of blood
cells.

As the child grows, most of the bone
marrow changes gradually into the yellow
variety.

Under certain conditions, such as severe
bleeding or hypoxia, yellow bone marrow
is replaced by red bone marrow.
Red Bone Marrow

Red bone marrow is composed of a stroma
, hematopoietic cords (or islands), and
sinusoidal capillaries.

The stroma is a three-dimensional
meshwork of reticular cells and a delicate
web of reticular fibers containing
hematopoietic cells and macrophages.

The stroma of bone marrow contains
collagen types I and III, fibronectin,
laminin, and proteoglycans.
Red Bone Marrow

The islands of hemopoietic cells are composed of
blood cells in various stages of maturation as well
as macrophages.

The macrophages destroy the extruded nuclei of
erythrocyte precursors, malformed cells, and
excess cytoplasm.

Macrophages also regulate hemopoietic cell
differentiation and maturation, transmit iron to
developing erythroblasts to be utilized in the
synthesis of the heme portion of hemoglobin.

Frequently, processes of macrophages penetrate
the spaces between endothelial cells to enter the
sinusoidal lumina.
HEMATOPOIESIS
Mature blood cells have a relatively short
life span, and the population must be
replaced with the progeny of stem cells
produced in the hematopoietic organs.
 In the earliest stages of embryogenesis,
blood cells arise from the yolk sac
mesoderm.
 Later, the liver and spleen serve as
temporary hematopoietic tissues.
 After Birth, the bone marrow becomes
an increasingly important hematopoietic
tissue.

Erythrocytes, granular leukocytes,
monocytes, and platelets are derived
from stem cells located in bone
marrow. The origin and maturation of
these cells are termed, respectively,
erythropoiesis, granulopoiesis,
monocytopoiesis, and
megakaryocytopoiesis.
 The bone marrow also produces cells
that migrate to the lymphoid organs,
producing the various types of
lymphocytes.

Stem Cells

Stem cells are pluripotential cells capable
of self-renewal.

Some of their daughter cells form specific,
irreversibly differentiated cell types.

Other daughter cells remain stem cells.

A constant number of pluripotential stem
cells is maintained in a pool, and cells
recruited for differentiation are replaced
with daughter cells from the pool.
Progenitor Cells

They have reduced potentiality and are
committed to a single cell linage.

They proliferate and differentiate into
precursor cells in the presence of
appropriate growth factors.

They are morphologically indistinguishable
(similar) to the stem cells, and both appear
similar to small lymphocytes.
Precursor Cells

precursor cells (blasts) have their own
morphological characteristics, and when
they differentiate for the first time, they
indicate the mature cell types which they
will become.

Whereas progenitor cells can divide and
produce both progenitor and precursor
cells, precursor cells produce only mature
blood cells.
Hemopoietic Growth Factors

Hemopoiesis is regulated by a number of
cytokines and growth factors, such as
interleukins, colony-stimulating factors (CSF,
macrophage inhibiting protein-a, and steel factor.

Hemopoiesis is regulated by numerous growth
factors produced by various cell types. Each
factor acts on specific stem cells, progenitor
cells, and precursor cells, generally inducing
rapid mitosis, differentiation, or both.

Some of these growth factors also promote the
functioning of mature blood cells. Most
hemopoietic growth factors are glycoproteins.
Hemopoietic Growth Factors

Certain growth factors such as steel factor
(also known as stem cell factor), granulocytemacrophage colony-stimulating factor (GMCSF) and two interleukins (IL-3 and IL-7)
stimulate proliferation of pluripotential stem
cells, thus maintaining their populations.

Additional cytokines, such as granulocyte
colony-stimulating factor (G-CSF), monocyte
colony-stimulating factor (M-CSF), IL-2, IL-5,
IL-6, IL-11, IL-12, macrophage inhibitory
protein-α (MIP-α), and erythropoietin, are
Hemopoietic Growth Factors

It has been suggested that there are
factors responsible for the release of
mature (and almost mature) blood
cells from the marrow.

These proposed factors have not yet
been characterized completely, but
Erythropoiesis

Erythropoiesis, the formation of red blood
cells, is under the control of several
cytokines, namely steel factor, IL-3, IL-9,
GM-CSF, and erythropoietin.

The process of erythropoiesis, red blood
cell formation, generates 2.5 × 1011
erythrocytes every day.

In order to produce such a huge number of
cells, two types of unipotential progenitor
cells arise from the CFU-GEMM (colonyforming units- granulocyte, erythrocyte,
Erythropoiesis

If the circulating red blood cell level is
low, the kidney produces a high
concentration of erythropoietin,
which, in the presence of IL-3, IL-9,
steel factor, and GM-CSF
(granulocyte-monocyte colony
stimulating factor), induces CFUGEMM to differentiate into BFU-E.
These cells undergo a "burst" of mitotic
activity, forming a large number of
Erythropoiesis

CFU-E require a low concentration of
erythropoietin not only to survive but also
to form the first recognizable erythrocyte
precursor, the proerythroblast.

The proerythroblasts and their progeny
form spherical clusters around
macrophages (nurse cells) which
phagocytose extruded nuclei and excess or
deformed erythrocytes.

Nurse cells may also provide growth
Monocytopoiesis

Monocytes share their bipotential cells with
neutrophils.

CFU-GM undergoes mitosis and gives rise to CFUG and CFU-M (monoblasts).

The progeny of CFU-M are promonocytes, large
cells (16 to 18 μm in diameter) that have a kidneyshaped, acentrically located nucleus.
Monocytopoiesis

Electron micrographs of promonocytes disclose a welldeveloped Golgi apparatus, abundant RER, and numerous
mitochondria.

The azurophilic granules are lysosomes, about 0.5 μm in
diameter.

Every day, the average adult forms more than 1010
monocytes, most of which enter the circulation.

Within a day or two, the newly formed monocytes enter
the connective tissue spaces of the body and differentiate
Platelet Formation

The formation of platelets is under the control of
thrombopoietin, which induces the development
and proliferation of giant cells known as
megakaryoblasts.

The unipotential platelet progenitor, CFU-Meg,
gives rise to a very large cell, the megakaryoblast
(25 to 40 μm in diameter), whose single nucleus
has several lobes.

These cells undergo endomitosis, whereby the
cell does not divide; instead, it becomes larger
and the nucleus becomes polyploid, as much as
Platelet Formation

The bluish cytoplasm accumulates azurophilic
granules. These cells are stimulated to
differentiate and proliferate by thrombopoietin.

Megakaryoblasts differentiate into
megakaryocytes , which are large cells (40 to 100
μm in diameter), each with a single lobulated
nucleus.

Electron micrographs of megakaryocytes display
a well-developed Golgi apparatus, numerous
mitochondria, abundant RER, and many
lysosomes .
Platelet Formation

Megakaryocytes are located next to sinusoids,
into which they protrude their cytoplasmic
processes. These cytoplasmic processes
fragment along complex, narrow invaginations of
the plasmalemma, known as demarcation
channels, into clusters of proplatelets.

Shortly after the proplatelets are released, they
disperse into individual platelets. Each
megakaryocyte can form several thousand
platelets.

The remaining cytoplasm and nucleus of the
megakaryocyte degenerate and are
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