Hemopoiesis pdf - Dr. Suhair Majeed

HEMOPOIESIS

BY
Dr. Suhair Majeed

HEMOPOIESIS :

Blood cells have a limited life span, and, as

a result, they are continuously replaced in the
body by a process called hemopoiesis. In this
process, all blood cells are derived from a
common stem cell in red bone marrow.
Because the stem cell can produce all blood
cell types, it is called the pluripotential
hemopoietic stem cell.

STEM CELLS

Are pluripotential cells that can divide

continuously and whose daughter cells form

specific , irreversibly differentiated cell types.

They reside in the medulla of the bone(bone

marrow) ,and have the unique ability to give rise to

all of the different mature blood cell types and

tissues.

self -renewing cells : when they proliferate,at

least , some of their daughter cells remain as

(stem cells ),so the pool of stem cells not become

depleted.

CONT.

Other daughters of stem cells (myloid and

lymphoid progenitor cells), they can commit to
any of the alternative differentiation pathways
that leads to the production of one or more
specific types of blood cells ,but they can not
self-renew.

CONT

Before maturation and release into the

blood stream, the stem cells from each line
undergo numerous divisions and intermediate
stages of differentiation .

Myeloid stem cells develop ed in red bone

marrow and give rise to erythrocytes, eosinophils,

neutrophils, basophils, monocytes, and

megakaryocytes..

CONT.

Lymphoid stem cells also developed in red

bone marrow. Some lymphoid cells remain in the
bone marrow, proliferate, mature, and become B
lymphocytes. Others leave the bone marrow and
migrate via the blood stream to lymph nodes and
the spleen, where they proliferate and
differentiate into B lymphocytes.

CONT.

Other undifferentiated lymphoid cells migrate

to the thymus gland, where they proliferate

and differentiate into T lymphocytes. Afterward, T

lymphocytes enter the blood stream and migrate
to specific regions of peripheral lymphoid organs.

Both B and T lymphocytes reside in numerous

peripheral lymphoid tissues, lymph nodes, and
spleen. Here, they initiate immune responses
when exposed to antigens.

HEMOPOIETIC TISSUES :

Specialized CT derived from mesenchyme ,

responsible for the production of new blood cells.
There are 2 types:

Myeloid Tissue (red bone marrow)_ responsible

for the production of most blood cell types.

LymphaticTissue(thymus,etc.)_responsible

for

formation of T- lymphocytes, proliferation of B-
lymphocytes,immune defences.

SITES OF HEMOPOIESIS :

Hemopoiesis occurs in different organs of the

body, depending on the stage of development. In

the embryo, hemopoiesis initially occurs in the

yolk sac and later in the liver, spleen, and lymph

nodes.

After birth, hemopoiesis continues almost

exclusively in the red marrow of different bones

(in the newborn, all bone marrow is red).

CONT.

The red bone marrow is highly cellular and

consists of hemopoietic stem cells and precursors

of different blood cells. Red marrow also contains

a loose arrangement of fine reticular fibers.

In adults, red marrow is found primarily in the

flat bones of the skull, sternum and ribs,
vertebrae, and pelvic bones. The remaining
bones, normally the long bones, gradually
accumulate fat, their marrow becomes yellow, and
they lose hemopoietic functions.

HEMOPOIESIS

ERYTHROPOIESIS:

Stages of development :

A- immature red cell precursors :

1- proerythroblast
2- basophilic erythroblast

B- mature red blood precursor cells :

3- polychromatic erythroblast
4- orthochromatic erythroblast
5- polychromatophilic erythrocyte (reticulocyte)
6- erythrocyte

ERYTHROPOIESIS (STAGES )

In normal state, the balance of production and

destruction is maintained at

constant rate .

The earliest recognizable erythroid precursor

seen in the bone marrow is large basophilic

staining cell ,Contains a single large well defined,

rounded nucleus,ribosomes, mitochondria and

golgi apparatus

CONT.

As the early precursor cell matures,

its

nucleus increases in size. As maturation goes

on cell becomes smaller and more eosinophilic

indicating hemoglobin.

During

intermediate stages of maturation,

cytoplasm becomes polychromatic indicating

mixture of basophilic proteins and eosinophilic

hemoglobin.

CONT.

Further maturation

, hemoglobin synthesis

continue and cytoplasm becomes entirely
eosinophillic.

Late stages of maturation

, hemoglobin is

abundant.few mitochondria and ribosomes are
present., nucleus is small dense and well
circumscribed.

STAGES OF ERYTHROPOIESIS

1- PROERYTHROBLAST

first erythrocyte precursor produced directly

from myeloid stem cell. They are characterized
by their size , and by having a very  dense
nuclear structure (large nucleus ),  with a
narrow layer of  cytoplasm (basophilic
cytoplasm ).

PROERYTHROBLAST

2- BASOPHILIC ERYTHROBLAST :

a strongly basophilic cytoplasm and a

condensed nucleus . Smaller than proerythroblast

The basophilia of these two cell types is caused

by the large number of polyribosomes involved in
the synthesis of hemoglobin.

BASOPHILIC ERYTHROBLAST

PROERYTHROBLAST VS BASOPHILIC
ERYTHROBLAST

3- POLYCHROMATIC ERYTHROBLAST :

Also called intermediate normoblast . Last

precursor cell capable of mitosis. Smaller than
basophilic erythroblasts .

Cytoplasm appears greyer because of presence

of haemoglobin .

POLYCHROMATIC ERYTHROBLAST

4- ORTHOCHROMATIC ERYTHROBLAST :

Also called late normoblast .Incapable of

cell division , the nucleus continues to
condense and an eosinophilic cytoplasm due
to abundant hemoglobin , this cell has a series
of cytoplasmic protrusions and expels its
nucleus,

ORTHOCHROMATIC ERYTHROBLAST

5- POLYCHROMATOPHILIC ERYTHROCYTE :

Also called reticulocyte .It’s formed when

the nucleus is extruded from the normoblast .

Named reticulocyte ,because the clustering

of ribosomes forms a reticular network.

Can carry oxygen and enter the blood stream

,they found in low concentrations in normal
blood .

POLYCHROMATOPHILIC ERYTHROCYTE
OR RETICULOCYTE

6- ERYTHROCYTE :

The final product of erythropoiesis is the

erythrocyte ,and it’s released from bone
marrow into the circulation

ERYTHROPOIESIS

NUTRITIONAL FACTORS

Normal erythrocyte production requires

protein, copper, iron, folic acid and vitamins B6
and B12. Deficiencies lead to inadequate
production of haemoglobin.

REGULATION :

Production of

erythrocytes

is regulated by

erythropoietin (EPO) which is produced in the yolk
sac,

liver

and kidney from embryonic life until

early neonatal life. In the adult it is produced only
in the kidneys. Erythropoietin is a glycoprotein
hormone . Normal levels are low with sufficient
amounts to maintain a basal level of new
erythrocyte production. If blood oxygen
concentration falls, the release of erythropoietin
rises.

DEVELOPMENT OF GRANULOCYTES

GRANULOPOIESIS

Committed myeloid stem cells differentiate

into three types of cells, neutrophils, Basophils
and eosinophils

STAGES OF DEVELOPMENT

A- immature white cell precursors :

1-myeloblasts
2-promyelocytes

B-partly mature white cell precursors :

1-myelocytes
2- metamyelocytes

C-mature neutrophils :

1-band cells
2-segmented neutrophils

1- MYELOBLASTS :

-The least mature cells in the granulocyte

lineage.Mononuclear,

- round –to –ovoid cells.
- Fine reticular nuclear structure and a

narrow layer of basophilic cytoplasm without
granules

MYELOBLAST

2- PROMYELOCYTE:

Are the product of myeloblast division .Usually

grow larger than their progenitor cells .Nucleus
is eccentric .Wide layer of basophilic cytoplasm.

PROMYELOCYTE

3- MYELOCYTES :

Are direct prduct of promyelocyte mitosis ,
Smaller than their progenitors.

Ovoid nucleus ,cytoplasm relatively basophilic

MYELOCYTE

NEUTROPHILIC MYELOCYTE VS
EOSINOPHILIC MYELOCYTE

4- METAMYELOCYTES :

Produced from final myelocyte division .
They are unable to divide ,from this stage ,only

further maturation of the nucleus occurs .

Nucleus slowly take on a kidney –bean shape.
Metamyelocyte is distiguished from a myelocyte

by incipient lobe formation .

METAMYELOCYTE

5- BAND CELLS :

Represent further development of

metamyelocytes .

The beginings of segmentation may be

visible, but the constriction should never cut
more than two – thirds of the way across the
nucleus .

BAND CELL

6- SEGMENTED NEUTROPHILS :

represent final stage in the lineage .

Nuclear segments are connected by narrow

chromatin bridges.

Cytoplasm is soft pink to colorless.

THROMBOPOIESIS

Megakaryocytes differentiate from myeloid

stem cell and are responsible for production of
platelets.

THREE STAGES OF MATURATION OF

MEGAKARYOCYTES

1-Basophilic stage, megakaryocyte is small, has

diploid nucleus and abundant basophilic
cytoplasm.

CONT.

2.Granular stage, here the nucleus is more

polypoid, cytoplasm is more eosinophilic and

granular

3.Mature stage, megakaryocyte is very large, with

approx 16-32 nuclei, abundance of granular

cytoplasm. It undergoes shedding to form

platelets.

MEGAKARYOCYTES :

-Reside in bone marrow .

-Cytoplasm with granules is pinched off from

megakaryocytes to form thrombocytes .

-Humoral factors regulate the increase of

megakaryocytes and the release of
thrombocytes when more are needed
(e.g.,bleeding or increased thrombocytes
degradation ).

MEGAKARYOCYTE

REGULATION

Thrombopoietin

is a glycoprotein hormone produced mainly

by liver and kidney that regulates the
production of platelets in bone marrow.

It stimulates the production and

differentiation of Megakaryocytes

PRODUCYION OF MONOCYTE :

The monoblast is a committed progenitor cell

that is identical to the myeloblast in its
morphology.

Further differentiation leads to the

promonocyte, a large cell with a basophilic

cytoplasm and a large, slightly indented nucleus.

Promonocytes divide twice in the course of their
development into monocytes.

CONT.

an extensive Golgi complex in which

granule condensation can be seen to be taking
place.

These granules are primary lysosomes,

which are observed as fine azurophilic granules
in blood monocytes.

Mature monocytes enter the bloodstream,

circulate for about 8 hours, and then enter the
connective tissues,where they mature into
macrophages and function for several months.

2- LYMPHOPOIESIS :

Circulating lymphocytes originate mainly in

the thymus and the peripheral lymphoid organs
(spleen, lymph nodes, tonsils, etc). It is probable,
that all lymphocyte progenitor cells originate in
the bone marrow. Some of these relatively
undifferentiated lymphocytes migrate to the
thymus, where they acquire the attributes of T
lymphocytes. Later, T lymphocytes populate
specific regions of peripheral lymphoid organs.

CONT.

Other bone marrow lymphocytes remain in the

marrow, differentiate into B lymphocytes, and
then migrate to peripheral lymphoid organs
where they inhabit and multiply in their own
special compartments.

The first identifiable progenitor of lymphoid

cells is the lymphoblast, a large cell capable of
dividing two or three times to form
prolymphocytes.

CONT.

These latter cells are smaller and have more

condensed chromatin but none of the cell-
surface antigens that mark prolymphocytes as T
or B lymphocytes. In the thymus or bone marrow,
these cells synthesize cell-surface receptors
characteristic of their lineage, but they are not
recognizable as distinct cell types using routine
histologic procedures.