HAEMATOPOIESIS

Haemopoiesis/ Haematopoiesis
• Haemopoiesis is the process of formation,
differentiation and development of blood cells.

• It starts during the embryonic development and

continues throughout adulthood to produce and
replenish the blood system.

• The study of haemopoiesis is of great importance in

day-to-day clinical work
• The study of haematopoiesis helps clinicians and
scientists to diagnose disease, understand the
processes of blood disorders and study the use of
stem cells for treatments

• The haematopoietic system consists of the bone

marrow, liver, spleen, lymph nodes, and thymus.

• The lifelong production of blood cells occurs in

haemopoietic tissue.
• This involves a very high level of cell turnover,
demanded by the need to replace mature
circulating blood cells at a rapid rate,

• and also is necessitated by the limited lifespan of

the mature cells.

• Granulocytes survive for only a few hours to days in

the peripheral blood and erythrocytes for a few
months.
• Averagely, human adults produce approximately
one trillion blood cells every day.

• This includes 200 billion erythrocytes (red blood

cells (RBCs)) and 70 billion neutrophils.

• These cells are produced daily in order to maintain

steady state levels in the peripheral circulation.
SITES OF HAEMOPOIESIS
• From 6 weeks until 6-7 months of fetal life the liver
and spleen are the major haemopoietic organs and
continue to produce blood cells until about 2
weeks after birth.

• The bone marrow is the most important site from

6 to 7 months of fetal life.

• During normal childhood and adulthood the

marrow is the only source of new blood cells.
• In infancy all the bone marrow is haemopoietic
but during childhood there is progressive fatty
replacement of marrow throughout the long
bones.

• In adult life haemopoietic marrow is confined to

the central skeleton and proximal ends of the
femurs and humeri.

• Even in these haemopoietic areas, approximately

50% of the marrow consists of fat.
• The remaining fatty marrow is capable of reversion
to haemopoiesis

• In many diseases there is also expansion of

haemopoiesis down the long bones.

• Moreover, the liver and spleen can resume their

fetal haemopoietic role ('extra-medullary
haemopoiesis').
• Extramedullary haemopoiesis occurs in the
following situations:

• When the bone marrow becomes dysfunctional in

cases such as aplastic anemia, infiltration by
malignant cells, or over-proliferation of a cell line
(e.g., leukemia).

• When the bone marrow is unable to meet the

demands placed on it, as in the hemolytic anemias
(e.g. sickle cell crisis)
 STEM CELLS
• Stem cells are cells that are capable of self-
renewal and differentiation when they divide and
are responsible for producing all the mature
blood cells throughout life.

• This means that when steady-state stem cells

divide, only 50% of the daughter cells, on
average, differentiate.

• The remaining 50% do not differentiate, but

maintain stem cell numbers.
STEM CELLS
 TYPES
• Totipotential stem cells. These cells are present in the
first few hours after an ovum is fertilized.
Totipotential stem cells, the most versatile type of
stem cell, can differentiate into embryonic and extra-
embryonic tissues such as chorion, yolk sac, chorion
etc which form the placenta.

• Pluripotential stem cells. These cells are present several

days after fertilization. Pluripotent stem cells can
develop into any cell type to form the tissue and
organs of the human being
• Multipotential stem cells. These cells are
derived from pluripotent stem cells. Multipotent
stem cells have the ability to develop into
specific types of cells.

• For example a blood stem cell (multipotent) can

develop into a red blood cell, white blood cell or
platelets (all specialized cells).

• There are multipotent stem cells for all of the

different types of tissue in the body.
• Oligopotent stem cells: These are able to self-renew
and form 2 or more lineages within a specific tissue.
Hematopoietic stem cells are a typical example of
oligopotent stem cells, as they can differentiate into
both myeloid and lymphoid lineages

• Unipotent stem cells can self-renew and differentiate

into only one specific cell type and form a single
lineage such as muscle stem cells, giving rise to
mature muscle cells and not any other cells.

• In tissues with a high cellular turnover, stem cell

populations are essential for lifelong maintenance of
organ function.
• The self renewal capabilities of the stem cell
ensures that marrow`s cellularity is kept constant in
a normal healthy steady state.

• This helps to offset the millions of blood cells that

are destroyed everyday.

• Stem cells are found in the haematopoietic

microenvironments, with few numbers circulating
in the peripheral blood.

• Stem and progenitor cells cannot be recognized

morphologically; they resemble lymphocytes.
• This number increases physiologically in some
circumstances, such as following exercise and during
infections.

• They may be also increased pharmacologically by

administration of haemopoietic growth factors and/or
cytotoxic chemotherapy.

• This phenomenon has been exploited to provide large

numbers of circulating stem cells, which can then be
collected by leucapheresis and used as a source of
cells for stem cell transplantation.
 HAEMOPOIETIC STEM CELLS (HSC)
• These form the foundation of the haemopoietic
system. These cells are characterized by their ability
to undergo self-renewal and multipotential
differentiation.

• The earliest HSC is the multipotent stem cell, which is

capable of giving rise to two committed stem cells:
namely, the lymphoid stem cell and the multi-potent
myeloid stem cell.
• The lymphoid stem cell gives rise to the
lymphocyte progenitor cell, which matures into
lymphocytes.

• The multi-potent myeloid stem cell gives rise to

various myeloid progenitor cells which eventually
matures into erythrocytes, neutrophils,
eosinophils, basophils and mast cells, monocytes
and platelets.
• The lymphoid and myeloid progenitor cells have
very limited capability for self-renewal.

• Immature myeloid progenitor cells are committed

to two or three differentiation pathways each.

• But as they mature they become committed to

one pathway i.e they become unipotent.
• Cell differentiation occurs from a committed
progenitor haemopoietic stem cell and one stem cell
is capable of producing about 106 mature blood cells
after 20 cell divisions.

• The precursor cells are, however, capable of

responding to haemopoietic growth factors with
increased production of one or other cell line when
the need arises.

• The proliferation and differentiation of haemopoietic

progenitor cells and the function of mature blood
cells is in turn regulated by glycoprotein hormones
called growth factors.
Growth Factors
• These are glycoproteins produced by stromal cells, T
lymphocytes, the liver and the kidney
(erythropoietin).

• GFs are produced by stromal cells in the

hematopoietic microenvironment.

• GFs interact with membrane receptors restricted to

cells of appropriate lineage.

• GFs commonly act synergistically with other

cytokines.
FUNCTIONS OF GROWTH FACTORS
• The first effect of GFs is to promote cell survival by
suppressing apoptosis.

• Second, GFs promote cell division and

proliferation of haematopoietic cells.

• GFs control and regulate the process of

differentiation, which ultimately produces the
mature functional cells.

• GFs sometimes enhance the activities of the

mature blood cells.
• Certain protein molecules called interleukins
work in conjunction with haematopoietic growth
factors to stimulate proliferation and
differentiation of specific cell lines.

• Interleukins are a group of cytokines that are

expressed and secreted by white blood cells as
well as other body cells.

• Interleukins are signaling molecules that act

independently or in conjunction with other
interleukins to encourage hematopoietic growth.
Growth factors in haemopoiesis
Growth factors
 Assessment of haemopoiesis
• Haemopoiesis can be assessed clinically by
performing a full blood count on peripheral blood or
examining a peripheral blood film.

• Bone marrow aspiration also allows assessment of the

later stages of maturation of haemopoietic cells.

• Trephine biopsy provides a core of bone and bone

marrow to show architecture.
 COMPLETE BLOOD COUNT
• The complete blood count (CBC) is one of the
most frequently ordered and most time-honored
laboratory tests in the hematology laboratory.

• This evaluation consists of several components

that offers the clinician a variety of hematological
data to assess bone marrow health and function.

• The CBC helps to detect quantitative

abnormalities in the blood cells.
Examination of Peripheral Blood
Film
• The examination of a stained peripheral blood
smear is an important component of the complete
blood cell count (CBC) procedure.

• Blood film examination helps to detect qualitative

abnormalities in blood cells.

• To identify normal cells, and detect abnormalities,

it is important to know the sequences of cellular
development by name as well as the general
maturational characteristics of blood cells.
Bone Marrow Aspiration
• Bone marrow aspiration is usually performed
on the back of the hipbone, or posterior iliac
crest

• Bone marrow examination is used in the

diagnosis of a number of conditions,
including leukemia, multiple myeloma,
lymphoma, anemia
Cellularity of the bone marrow
• This is one of the most important factors in
evaluating the function of bone marrow

• It is a measure of the ratio of hematopoietic cells to

adipocytes

• Normocellular bone marrow shows a ratio of 50%

: 50%
• Hypocellular bone marrow – small number of
blood forming cells can be found (example after
chemotherapy, aplastic anemia, ...)

• Hypercellular bone marrow –typically as a result of

tumors originating from hematopoietic cells