Hematopoeisis or
hemopoeisis is the presence of blood cells production by the blood forming
organs.
Erythropoeisis – process
of producing red blood cells
Leukopoeisis – process of
producing white blood cells
Myelopoeisis – process of
producing granulocytes
Lymphopoeisis – process of
producing lymphocytes
Thrombopoeisis – process
of producing thrombocytes or blood platelets
The hematopoietic system
is highly specialized for both the production of new blood cells and the
removal of those which are old and worn out. To keep the total number of cells fairly
constant, new ones must be added to the blood each day to replace the old ones
which are removed.
Undifferentiated cells of
the mesenchyme and endothelial cells of the primitive blood spaces give rise to
blood cells in the embryo. Later, in due course, production of blood cells
becomes organoid and the liver and spleen become the main sites. Eventually,
the bone marrow takes over. At birth, the marrow is active and red and contains
only minimal amounts of fat. Later in childhood, only the proximal portions of
the long bones and the flat bones are the sites of blood formation. The rest of
the marrow space is occupied by fat, which can be replaced by hemopoeitic cells
when the need arises.
Hematopoietic tissues –
organs or tissues in which blood cell production occurs are known as
hematopoietic tissues. Based on the organs and tissues involved, hematopoiesis
may be called:
1. Medullary hematopoiesis
This
involves the formation of normal red blood cells in the marrow. It is limited
to the vertebrae, ribs, sternum, pelvis, scapulae, skull and extreme portions
of humeri and femora. In infants and children, active hematopoiesis takes place
in more distal portions of the extremities than in adults. Hematopoiesis occurs
within the parenchyma of the bone marrow bounded by sinusoids.
The
red bone marrow – produces red cells,
platelets, neutrophils, eosinophils and basophils and serves as one of the
sites of formation of lymphocytes, monocytes and plasmacytes.
The
yellow bone marrow – is filled with
fat. This fat occupies reserve space and readily goes into solution and
disappears as the blood cells increases, thus making it possible for
regeneration to occur on demand without interfering with vital structures.
2. Extramedullary hematopoiesis
This
involves the formation of normal red blood cells outside the confines of the
bone marrow. The spleen is the most commonly encountered site, but
hematopoiesis in liver, lymph nodes and in the islands of the lymphatic tissue
and less commonly adrenal glands, cartilage, broad ligament, thrombi, adipose
tissue, intrathoracic tissue, kidneys and endosteum. These hematopoietic areas
may be composed of pure or mixed erythrocytic, leukocytic or megakaryocytic
tissue.
Lymphatic
system – the lymphocytes are formed
in the most part in the lymph nodes and in the island of lymphatic tissue
located in the spleen, bone marrow, thymus, liver and intestinal tract and to a
lesser extent in practically over other organ except the brain and spinal cord.
Spleen
– it aids in the formation of
lymphocytes and monocytes and serves as a reservoir for cells which can be
delivered from the pulp into the circulation on demand.
Stomach – secretes the intrinsic factor, the presence of
which is essential in the absorption of Vitamin B12 from the
intestinal tract. Vitamin B12 is a requirement for the normal
maturation of erythrocytes.
THEORIES OF BLOOD CELL DEVELOPMENT
There are two broad
theories or schools of thought regarding the development of cells:
1. Unitarian theory states that
all blood cells are derived from a hemohistioblast (reticuloendothelial stem
cell) which is capable of giving rise to several types of cells.
2. Polyphyletic theory states
that the first recognizable and most primitive blood cells are already
differentiated and their future development along one line is already
determined.
In
any case, all cells arise from the stem cell.
In
man, all blood cells are derived from a pluripotential stem cell. A stem cell
possesses 2 different properties:
a. Property of proliferating by
mitosis
b. Property of continuing to
differentiate, i.e., to mature along a cell line, during which process the various
more mature forms retains only a limited proliferative capacity. Pluripotential
means that this stem cell has the ability to differentiate into a number of
possible cell series. In other words, it may evolve in the direction of
megakaryocytes or in the direction of monocytes. Although a unipotential cell
can divide and thus ensure the continuation of this type of cell; it can also
continue to differentiate along a specific line of cells. A myeloblast, for
instance, will only give rise to granulocytes, a proerythroblast only to
erythrocytes. These stem cells are also known as “committed stem cells”
(pluripotential stem cell) to change into a “committed stem cell” are
imperfectly understood.
MATURATION OF BLOOD CELLS
Principle of normal
cell maturation
In any series of cell
development, an almost infinite gradation of cells exists between the most
immature “blast” form and the mature definitive cells. The mature cell is
identified and characterized by certain specific features which develop during the
course of maturation. These features gradually appear as the cell matures so
that each nucleus must evolve gradually and appear at some stage of maturation.
Since this is a normal and orderly process, blood cells exhibit constant
features which lead to the description of typical stages. Since a cell is
composed of several components or structures, each of these parts undergoes
individual transformation. Normally, these transformations or changes occur
simultaneously (synchronism) which simplifies description. Abnormal cell
maturation may be characterized by different rates of maturation of the
different parts (asynchronism) producing cells that are “atypical” or bizarre
but whose external structure is easily analyzed as that of normal cell.
There are three changes
that always occur in the transformation from an immature to a mature cell:
1. Cytoplasmic changes
a. Loss of basophilia – the cytoplasm of an immature cell is usually blue
or basophilic due to its ribonucleic acid (RNA) content. The more mature the
cell, the less basophilic because of the less RNA content.
b. Cytoplasmic granules – in myeloid cells, the cytoplasm is studded with
granules. These granules contain some enzymes which distinguish the myeloid
stem cells from other cells. Those which have affinity to the red acidic dye
are called acidophilic or eosinophilic granulocytes. Those which
have affinity to the blue basic dye are called basophilic granulocytes
and those that have affinity to both the acid and basic dyes are called neutrophilic
granulocytes.
c. Elaboration of hemoglobin – this is a special feature of the maturation of
erythrocytic cells. At first, the immature cell contains no hemoglobin.
Gradually, the hemoglobin starts to appear as the cell becomes mature until the
most mature cell contains a standard and maximal amount of it. At the mature
stage the nucleus is apparently no longer necessary and is eliminated by
nucleolysis or extrusion.
2.
Nuclear changes
a. Structure and cytochemistry – the immature nucleus is round or oval and the
nuclear chromatin is very delicate. As the cell matures, the chromatin strands
become increasingly coarse and clumped and there is also a reduction in the
number of nucleoli.
b. Shape changes – as the cell mature, the shape of the nucleus changes too. This is
especially true with granulocytes in which the nucleus divides into segments or
lobes as it grows older. The older the cell, the more segments or lobes the
nucleus has.
3. Reduction of cell size – it is a feature of all cells except megakaryocytic
series in which the immature cell is smaller than the fully developed
megakaryocyte. Generally speaking, a mature cell is smaller than an immature
one.
Principle of abnormal
cell maturation
Pathologic hematopoiesis
results in abnormal nuclear maturation, abnormal cytoplasmic differentiation
and abnormal size. Their development may also be asynchronous.
1. Abnormal cytoplasmic differentiation – in erythrocytes, this is characterized by
persistent cytoplasmic basophilia and late hemoglobinization. Abnormal
cytoplasmic inclusion bodies may be found in the cytoplasm of both erythrocytes
and leukocytes, especially in the granulocytes.
2. Abnormal nuclear maturation – in leukemia and other severe disturbances, two
nuclei may be present; one may be diploid and other polyploid. The nucleus may
be hypersegmented or hyposegmented.
3. Abnormal size
– abnormally large cells are frequently seen in benign or malignant
proliferation. In erythrocytic series, the megaloblasts are larger than normal
and are even present in the mature erythrocyte. Likewise, abnormally small
cells may be found.
STEM CELLS
In postnatal life in
humans, erythrocytes, granulocytes, monocytes and platelets are normally
produced in bone marrow. Lymphocytes are produced in the secondary lymphoid
organs, as well as in the bone marrow and thymus gland.
Most bone marrow cells are
morphologically recognizable precursors of granulocytes, erythrocytes or
platelets. A fraction of cells in adult marrow is identifiable only as
lymphocytes. Smaller number of monocytes, macrophages, endothelial cells and
plasma cells are noted.
Stem cells can both
reproduce themselves and give rise to more differentiated cells; they are not
morphologically identifiable as stem cells. A pluripotential or multipotential
stem cell is present in the marrow and gives rise to two major progenitors, the
lymphoid stem cells and myeloid or hematopoietic stem cell. The latter is a
common precursor cells for granulocytes and monocytes, erythrocyte and
megakaryocytes.
Committed progenitor cells
(committed stem cells) are characterized by their ability to form colonies in
vitro in response to a soluble factor.
It is believed that the
pluripotential hematopoietic stem cell is induced by certain microenvironmental
influences to become the committed erythroid progenitor cell.
The committed progenitor
cell for neutrophils and monocytes divides and gives rise to the myeloblast,
the earliest recognizable granulocyte–monocyte precursors, under stimulation by
a hormone, colony– stimulating factor for granulocytes and monocytes.
Monocytes share the same
committed progenitor cell as neutrophils, the GM – CFC.
Platelets originate from
polyploid megakaryocytes, the largest of all hematopoietic cells, which number
less than 1% of the total nucleated marrow cells. They arise from the
multipotential hematopoietic stem cells, probably directly from a committed
progenitor cells.
According to current
concepts, during fetal life, lymphocyte precursors originate in the bone marrow
and are influenced or programmed to perform a certain function by one of the
primary lymphoid organs, either the thymus gland for T–lymphocytes (T–cells) or
the “bursal equivalent” for B– lymphocytes (B–cells)
NORMOBLASTIC MATURATION
RUBRIBLAST
Synonyms: Proerythroblast or Pronormoblast
Size: 14 – 19 micrometers
Nucleus: round or oval; thin membrane; central
or slightly eccentric
Chromatin: fine to coarse; scanty and indistinct
Nucleoli: 1 – 2; usually pink
Cytoplasm: small, moderately basophilic, homogenous
and opaque
N/C ratio: 8:1
PRORUBRICYTE
Synonyms: Early erythroblast
Basophilic normoblast
Basophilic erythroblast
Size: 10 – 15 micrometers
Nucleus: smaller than pronormoblast, round and
slightly eccentric with thin membrane
Chromatin: irregular and coarse; sparse but distinct
Nucleoli: 0 – 1
Cytoplasm: apparently abundant; royal blue and opaque,
with varying amounts of
hemoglobin; with Reddish tinge
N/C ratio: 6:1
RUBRICYTE
Synonyms: Polychromatophilic erythroblast
Polychromatophilic normoblast
Intermediate erythroblast
Intermediate normoblast
Size: 8 – 12 micrometers
Nucleus: round, smaller than prorubricyte;
eccentric; thick membrane
Chromatin: coarse and clumped; irregularly condensed;
distinct parachromatin
Nucleoli: no longer visible
Cytoplasm: relatively more abundant; varying mixture
of red and blue to diffusely lilac
N/C: 4:1
METARUBRICYTE
Synonyms: Orthochromatic erythroblast
Orthochromatic normoblast
Late erythroblast
Late normoblast
Size: 7 – 10 micrometers
Nucleus: small, shrunken, solid black;
degenerated
Chromatin: non–linear clumped and condensed
Nucleoli: none
Cytoplasm: red with minimal amounts of residual blue
RETICULOCYTE
Synonyms: Diffusely basophilic erythrocyte
Polychromatophilic erythrocyte
Vital granulated erythrocyte
Vital staining erythrocyte
Pro–erythrocyte
Size: 8
– 10 micrometers
Nucleus: none, instead, after supravital stain
center of cell shows network of fibrillae and
dots or Reticulum of bluish tint (residue of
RNA)
Chromatin: None
Nucleoli: None
Cytoplasm: pink to reddish brown
ERYTHROCYTE
Synonyms: Normocyte, akaryocyte, red blood cell,
erythroplastid
Size: 6 – 8 micrometers
Nucleus: None
Chromatin: None
Nucleoli: None
Cytoplasm: Pink, darker in periphery than in the
center
MATURATION OF
GRANULOCYTE
MYELOBLAST
Size: 10 – 20 micrometers
Nucleus: Round or oval, thin nuclear membrane;
stippled finely reticulated; light purple
Chromatin: abundant chromatin, pale blue or pink
parachromatin
Nucleoli: 2 – 5 round or oval; pale blue
Cytoplasm: sparse, deeply basophilic; no granules
N/C ratio: 7:1
PROMYELOCYTE
Synonyms: Progranulocyte
Size: 14 – 20 micrometers
Nucleus: large, round or oval, thin membrane
Chromatin: slightly clumping
Nucleoli: 1 – 3; pale blue; round or oval
Cytoplasm: sparse; basophilic, contains slight
purplish granules
N/C ratio: 5:1
MYELOCYTE
Size: 10 – 19 micrometers
Nucleus: round or oval
Chromatin: Coarse condensed chromatin with blue or
pink parachromatin
Nucleoli: Rarely more than one; usually not
visible
Cytoplasm: moderate amount; large granules – purplish
blue at early stage; granules turn
eosinophilic or basophilic or neutrophilic in
the late or more mature stage.
N/C ratio: 2:1
METAMYELOCYTE
Synonym: Juvenile
Size: 10 – 28 micrometers
Nucleus: Indented and kidney – shaped
Chromatin: Deep purple; coarse and more clumped;
scanty parachromatin
N/C ratio: 1:5:1
Nucleoli: Not visible
Cytoplasm: Fairly abundant; pink with eosinophilic or
basophilic or neutrophilic granules
BAND
Synonyms: Stab, Staff cell
Size: 10 – 15 micrometers
Nucleus: Sausage shaped; band shaped or shaped
like letters C,S,Z; curved rod
Chromatin: coarse chromatin; deep purplish blue
Nucleoli: Not visible
Cytoplasm: Abundant; pale blue or pink with
neutrophilic, eosinophilic or basophilic granules
N/C ratio: 1:2
SEGMENTED GRANULOCYTE
Synonym: Polymorphonuclear neutrophil, basophil
or eosinophil
Size: 10 – 15 micrometers
Chromatin: Coarse, dense, deep purplish blue
Nucleus: Two or more lobes or segments
connected by filaments
Nucleoli: Not visible
Cytoplasm: Abundant; blue or pink with characteristic
eosinophilic [red, neutrophilic (lilac) or
Basophilic (dark blue or blackish) granules
N/C ratio: 1:3
Eosinophils rarely have
more than 2 segments; usually nucleus lies over the granules are coarse and
red. Basophils usually have indented nucleus, rarely more than 2 segments,
usually the granules are found lying over the nucleus; granules are coarse and
dark blue.
Neutrophils have nuclei
with more than 2 segments as much as 5. Granules are lilac and finer.
MATURATION OF
LYMPHOBLAST
LYMPHOBLAST
Size: 10 – 18 micrometers
Nucleus: Centrally located; definite membrane,
round or oval
Chromatin: Thin strands or light red purple chromatin
Light blue sharply demarcated parachromatin
Nucleoli: 1 – 2 small pale blue
Cytoplasm: Homogenous and moderately basophilic;
sparse with no granule
N/C ratio: 7:5
PROLYMPHOCYTE
Size: 10 – 18 micrometers
Nucleus: Round or oval; slightly indented
Chromatin: Reddish – purple densed chromatin;
parachromatin not well defined
Nucleoli: One, round, blue and well outlined
Cytoplasm: Moderately abundant; pale blue to medium
dark blue
N/C ratio: 5:1
LYMPHOCYTE
Size: Small lymphocyte – 6 – 8
micrometers
Large lymphocyte – 8 – 18 micrometers
Nucleus: Round or oval, slightly or deeply
indented, eccentric, heavy membrane, closely
knit
Chromatin: Large coarse clumps of chromatin blending
into sparse pale blue to pink
parachromatin
Nucleoli: Generally none, occasionally present
Cytoplasm: Clear, homogenous Robin’s egg blue or sky
blue with occasional azurophilic
granules
N/C ratio: 5:2
MATURATION OF MONOBLAST
MONOBLAST
Size: 12 – 18 micrometers
Nucleus: pale staining and indented; fine
strands of chromatin, abundant parachromatin
Nucleoli: Usually none; occasionally one
Cytoplasm: Gray blue; opaque with numerous fine
dustlike lilac granules
N/C ratio: 6:1
PROMONOCYTE
Size: 14 – 18 micrometers
Nucleus: Moderately indented; thin membrane
Chromatin: Fine, thread – like chromatin; abundant
parachromatin
Nucleoli: 0 – 1
Cytoplasm: Opaque, gray blue with very fine lilac
granules
N/C ratio: 5:1
MONOCYTE
Size: 12 – 18 micrometers
Nucleus: Indented or folder over; delicate pale
staining; kidney shaped; with brain – like
Convolutions; sprawling with blunt pseudopods
Chromatin: Fine strands; abundant and distinct
parachromatin
Nucleoli: Occasionally blue; usually none
Cytoplasm: Abundant; slightly gray ground glass
appearance
N/C ratio: 4:1
MATURATION OF MEGAKARYOBLAST
MEGAKARYOBLAST
Size: 25 – 35 micrometers
Nucleus: Large oval or round
Chromatin: Delicate purple chromatin; sparse
parachromatin
Nucleoli: 2 – 6; small and indistinct
Cytoplasm: Scanty; irregular; blue non–granular with
blunt pseudopods with various shades
of Blue; may contain azurophilic granules
N/C ratio: 10:1
PROMEGAKARYOCYTE
Size: 25 – 60 micrometers
Nucleus: Irregularly large; single but may
appear lobulated or multilobulated
Nucleoli: 2 – 6 small indistinct
Cytoplasm: Basophilic; prominent blue to reddish
purple granules and marginal bubbly
cytoplasm
N/C ratio: 6:1
MEGAKARYOCYTE
Size: 40 – 150 micrometers
Nucleus: multiform resembling staghorn calculi;
irregular bizarre
Chromatin: Coarse; irregularly clumped
Nucleoli: Usually not visible
Cytoplasm: Abundant, pale with fine blue granules and
showing pseudopod – like
projections
N/C ratio: 1:2
The granular megakaryocyte
is characterized by spreading of the red pink granules diffusely through most
of the cytoplasm and further increase and spreading of nuclear lobes. In the
mature megakaryocyte, the nucleus is more compact, basophilia has disappeared,
and the granules are clustered into small aggregates. At an ultrastructural
level, this is produced by proliferation in invaginated surface membrane
(demarcating membrane) that separates the cytoplasm into individual platelets.
Platelets are ultimately shed as cytoplasmic fragments by fusion of demarcation
membranes. In the marrow, megakaryocytes are adjacent to sinus walls, and
platelets are released into the lumen.
THROMBOCYTE
Synonym: Blood platelet
Size: 2 – 5 micrometers
Nucleus: None
Nucleoli: None
Cytoplasm: Light blue with granules at the center
(granulomere, chromomere), marginal
zone – Hyalomere
MATURATION OF
PLASMABLAST
PLASMABLAST
Size: 15 – 25 micrometers
Nucleus: Round or oval; eccentric
Chromatin: Coarse and reticulated; moderate amount and
distinct parachromatin
Nucleoli: 2 – 4
Cytoplasm: Fairly abundant, moderately or deeply
basophilic with no granules
N/C ratio: 1:2
PROPLASMACYTE
Size: 15 – 25 micrometers
Nucleus: Oval or rough; eccentric; moderately
coarse
Chromatin: Intermediate
Nucleoli: 1 – 2; very large when abnormal
Cytoplasm: Brilliant blue; opaque
N/C ratio: 1:2
PLASMACYTE
Synonym: Plasma cell
Size: 10 – 20 micrometers
Nucleus: Round or oval; eccentric, dense and
concentrated in the periphery creating the
so called “cart–wheel” or “spokes of a wheel”
arrangement
Nucleoli: None
Cytoplasm: Dark blue; ovoid and somewhat fibrillary
with pale clear perinuclear zone;
non–granular but may contain secretory globules called
“Russell bodies” which
may
be colorless, red, pink, blue or green in color. If globules fill the
cytoplasm, cell is called “grape or berry or morula” cell. The intracytoplasmic
deposition or amorphous material gives rise to Mott cell or Flame cell
N/C ratio: 1:2
No comments:
Post a Comment