Hematology – Lecture

Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022

HEMATOPOIESIS: C. Liver
The Formation and Development of Blood Cells
Hematopoiesis is a continuous, regulated process of blood D. Thymus – responsible for normal development of some of the
cell production that includes cell renewal, proliferation, lymphocytes
differentiation, and maturation.
THEORIES OF BLOOD CELL PRODUCTION
These processes result in the formation, development, and
specialization of all of the functional blood cells that are released
from the bone marrow to the circulation. A. MONOPHYLETIC
- All blood cells are derived from uncommitted stem cells
• A continuous, regulated process of blood cell production which are capable of giving rise to several types of cells.
that includes cell renewal, proliferation, differentiation, and B. POLYPHYLETIC
maturation. - The first recognizable and most primitive blood cells are
already committed to develop into a specific cell line.
• Process of blood cell production in the blood forming
organs STEM CELLS AND PROGENITOR CELLS
STAGES OF HEMATOPOIESIS
I. Pre-Natal Hematopoiesis 1.HEMATOPOIETIC STEM CELLS (HSCs)
II. Post-Natal Hematopoiesis - Earliest/primitive cells
- Divide by mitosis to give rise to multipotent progenitors
- Have the morphology of blasts
PRE-NATAL HEMATOPOIESIS
- Express CD34 but lacks MHC Class II antigen
2. UNIPOTENT PROGENITORS
I. MESOBLASTIC PERIOD - Starts to commit, as they mature it acquires more cluster
• Starts on 14th day, peaks on the 1st month and persist up of differentiation (CD), remain CD34 (immature) for ID,
to 3rd month of gestation serotest and morphology
• Chief site – Blood islands of yolk sacs - Include common myeloid and lymphoid progenitor cell
• 3rd month fetal life = Primitive Erythroblast 3. LINEAGE COMMITTED PRECURSOR
- Recognize due to additional expression of antigens
• Primitive Erythroblast
(CD38)
o Formed intravascularly, megaloblastic, and
o CD71 – erythroid CD10 – B cells
retain their nuclei
o CD33 – myeloid
o Contains Embryonic Hemoglobin
CD7/CD5 – T cells
II. HEPATIC PERIOD
• Starts on the 5th week, peaks on the 6th month and persist CHARACTERISTICS OF BLASTS CELLS
up to birth 1. Size – generally large with high nuclei and cytoplasmic ratio
• Chief site – Liver, as well as spleen and lymph nodes
(lesser extent) 2. Cytoplasm – basophilic, small in amount, no granules
• Definitive Erythroblasts
o Formed extravascularly and extrude their 3. Nucleus – large and round to oval in shape
nucleus **Chromatin (Euchromatin) – very fine, very smooth,
o Contains Fetal hemoglobin (HbF) reddish purple, no clumping of chromatin materials
III. MEDULLARY PERIOD
• Starts on the 5th month of fetal life up to adulthood **Nucleoli – pale light blue, capable of mitosis
• Chief site – Bone Marrow
• Erythroblasts SYNCHRONISTIC MATURATION
o HbA1 - begins to appear and gradually increases
in concentration
A. CYTOPLASMIC CHANGES
POST – NATAL HEMATOPOIESIS 1. Loss of Basophilia – decrease in RNA as cell mature

2. Cytoplasmic Granules – special feature of granulocytic series

I. MEDULLARY
3. Elaboration of hemoglobin – special feature of erythrocytic
Bone Marrow – is the only site of erythropoiesis, myelopoiesis and
series
thrombopoiesis
B. NUCLEAR CHANGES
• Red Bone Marrow – Hematopoietically active marrow
1. Structure and Cytochemistry – most reliable criterion
• Yellow Bone Marrow – composed primarily of
adipocytes (fats) 2. Number of Nucleoli – decreases nucleoli and amount of
II. EXTRAMEDULLARY ribosome
Blood cell production in hematopoietic tissue other than bone
marrow 3. Shape

A. Lymphatic System o Granulocytes – Indentation and Segmentation, most

number of lobes (mature)
B. Spleen – most common encountered site that aids in the o Erythrocytes – Pyknotic, and is eventually extruded at
formation of Lymphocytes and Monocytes orthochromatic stage
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
C. REDUCTION IN CELL SIZE
Special feature of all cell lineage except megakaryocytes

General Rule: As the cell matures, the size, basophilia of cytoplasm

and number of nucleoli decreases while coarseness of chromatin
increases.

ASYNCHRONISTIC MATURATION ERYTHROCYTE NORMAL MATURATION SERIES

1. ABNORMAL CYTOPLASMIC MATURATION PRONORMOBLAST (RUBRIBLAST) (PROERYTHROBLAST)

• Persistent cytoplasmic basophilia – should be decrease • Size: 12-25 um in diameter
or lost • Cytoplasm:
• Late hemoglobinization – erythrocytic series o Deeply basophilic
• Inclusion bodies – (erythrocytes, granulocytes) remnants o Relatively small amount
of cell organelle, microorganism, parasites, iron deposits ▪ Perinuclear halo
2. ABNORMAL NUCLEAR MATURATION • Nucleus
• Polyploidy (megakaryocytic cells) – 2 nuclei in 1 cell, o Large
myeloid precursor o Round to sl. Oval
• Hyposegementation or Hypersegmentation – excess o Reddish purple
lobes, infectious and toxic substances o 1-3 nucleoli
• Delayed Maturation – megalocyte (blast), smaller, takes • N/C ratio: 8:1
longer time to mature than its cytoplasm • 1% of nucleated cells in bone marrow
3. ABNORMAL SIZE
• Large atypical lymphocytes BASOPHILIC NORMOBLAST (PRORUBRICYTE)
• Megalocytes or Macrocytes (BASOPHILIC ERYTHROBLAST)
• Size: 12-17 um in diameter
• Micromegakaryocytes
• Cytoplasm: intensely basophilic
REGULATION OF HEMATOPOIESIS • Nucleus:
o Relatively large
o Round to slightly oval
QUALITATIVE AND QUANTITATIVE CELLULAR o Coarser chromatin
EQUILIBRIUM o Indistinct nucleoli
Balance between qualitative and quantitative parameters o Occupies 75% of the cell
o Qualitative – normal morphology (size and shape)
o Quantitative – normal count • 1-3% of nucleated cells of bone marrow
• Erythropoietin (EPO) - major regulator of erythropoiesis, POLYCHROMATOPHILIC NORMOBLAST (RUBRICYTE)
stimulates erythroid CFU cells and proerythroblasts (POLYCHROMATOPHILIC ERYTHROBLAST)
• Thrombopoietin (TPO) - increases platelet production, • Size: 12-15 um in diameter
stimulates megakaryocyte CFU cells • Cytoplasm: blue-gray to pink gray
• Granulocyte CSF (G-CSF) - increases production of • (production of hemoglobin)
neutrophils, stimulates granulocyte-macrophage CFU • Nucleus:
cells o Round, eccentric
• Granulocyte-macrophage CSF (GM-CSF) - increases o Smaller
macrophage production, stimulates granulocyte- o More condensed
macrophage CFU cells o Stains deeper blue-purple
• Interleukins - stimulate B- and T-cell formation, function • 13-30% of nucleated cells in
together with G-CSF and GM-CSF • bone marrow
ERYTHROPOIESIS • This is the last cell division during maturation
• A hemocytoblast is transformed into a proerythroblast ORTHOCHROMIC NORMOBLAST
• Proerythroblasts develop into early erythroblasts (METARUBRICYTE) (ORTHOCHROMIC ERYTHROBLAST)
• Size: 8-12 um in diameter
The developmental pathway consists of three phases:
• Cytoplasm: pinker, increased amount of Hb
1 – ribosome synthesis in early erythroblasts • Nucleus:
o Pyknotic
2 – Hb accumulation in late erythroblasts and o eccentric
• 1-4% of nucleated cell in bone marrow
normoblasts
• Nucleus is extruded at this stage
3 – ejection of the nucleus from normoblasts
RETICULOCYTE
and formation of reticulocytes Diffusely Basophilic Erythrocyte*

** Reticulocytes then become mature erythrocytes Polychromatophilic Erythrocyte*

• Size: 7-10 mm in diameter

• Cytoplasm:
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
o Pink to pinkish grey
o Still contains small amounts of RNA
(polychromasia)
o Nucleus: none
• Within 24-48 hrs, the cell loses the organelles & assumes
a biconcave shape
ERYTHROCYTE
• Size: approximately 7.2 um in diameter
• Cytoplasm: Pink
• The red blood cell is non-nucleated, round and biconcave
THE LIFE CYCLE OF A RED BLOOD CELL
a. Kidneys respond to a lower than normal oxygen concentration
in the blood by releasing the hormone erythropoietin.
b. Erythropoietin travels to the red bone marrow and stimulates an
increase in the production of red blood cells (RBCs).
c. The red bone marrow manufactures RBCs from stem cells that
live inside the marrow.
d. RBCs squeeze through blood vessel membranes to enter the
circulation.
e. The heart and lungs work to supply continuous movement and
oxygenation of RBCs.
f. Damaged or old RBCs are destroyed primarily by the spleen.
** 120 DAYS – LIFE SPAN OF RED CELL IN PERIPHERAL
BLOOD.
NUTRITIONAL REQUIREMENTS
- Proteins, lipids, and carbohydrates
- Iron, vitamin B12, and folic acid
- The body stores iron in Hb (65%)
• Intracellular iron is stored in protein-iron complexes such
as ferritin and hemosiderin
• Circulating iron is loosely bound to the transport protein
transferrin
ORGANS INVOLVED IN ERYTHROPOIESIS
REGULATION OF ERYTHROPOIESIS
• Too few RBCs leads to tissue hypoxia
• Too many RBCs increases blood viscosity
• Balance between RBC production and destruction
depends on:
o Hormonal controls
o Adequate supplies of iron, amino acids, and B
vitamins
HORMONAL CONTROL OF ERYTHTOPOIESIS
• Erythropoietin (EPO)
o Direct stimulus for erythropoiesis
o Released by the kidneys in response to hypoxia
• Causes of Hypoxia
o Hemorrhage or increased RBC destruction
reduces RBC numbers
o Insufficient hemoglobin (e.g., iron deficiency)
o Reduced availability of O2 (e.g., high altitudes)
• Effects of EPO
o More rapid maturation of committed bone
marrow cells
o Increased circulating reticulocyte count in 1–
2 days
• Testosterone also enhances EPO production, resulting in
higher RBC counts in males
ERYTHROCYTE MEMBRANE
Functions:
• Maintain cell shape and deformability
• Maintain osmotic balance bet. Plasma and the cell
cytoplasm
• Act as a supporting skeletal system for surface antigens
and receptors
• Aid in the transportation of essential cellular ions and
gases
Composition
• Proteins~50%
• Lipids ~ 40%
• Carbohydrates~10%
COMPOSITION OF THE ERYTHROCYTE MEMBRANE
CARBOHYDRATES
• They occur only on the external surface of the red cell.
• They occur as glycoprotein and glycolipids.
• The antigens of the ABO blood group are examples
of membrane carbohydrates.
LIPIDS
• Lipid components of the red cell membrane are:
o 30% free unesterified cholesterol
o 10% Glycerides and free fatty acids
o 60% Phospholipids
Phospholipids
o Phospholipids are fat derivatives in which one fatty acid
has been replaced by a phosphate group and one of
several nitrogen-containing molecules.
o Phospholipid molecules are characterizedby a polar
head group attached to a non-polar fatty acid tail
CHOLESTEROL
• The membrane cholesterol is unesterified and lies
between the two layers of the lipid bilayer.
• The cholesterol molecule inserts itself in the membrane
with the same orientation as the phospholipid molecules.
• The concentration of cholesterol in the membrane is an
important determinant of membrane surface area and
fluidity.
• An increase in membrane cholesterol leads to an
increased surface area and decreased deformability.
• In extreme circumstances, decreased deformability
can lead to premature RBC destruction.
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
PROTEINS - Integral proteins contain sialic acid which gives
erythrocytes a negative charge
• These are either: - Phospholipids in the cell membrane tend to arrange
o -Peripheral or themselves in a bilayer.
o -Integral - Hydrophilic heads pointing towards the inner and outer
aqueous phases ( the cytoplasmic and extracellular
Peripheral Proteins
phase),
• The red cell peripheral proteins interact to form a - The hydrophobic tails point towards each other.
cytoskeleton. - @The membrane cholesterol is unesterified and lies
between the two layers of the lipid bilayer.
• The cytoskeleton acts as a tough supporting framework
- The cholesterol molecule inserts itself in the membrane
for the lipid bilayer.
with the same orientation as the phospholipid molecules
• Four peripheral proteins play a key role in the structure of
the red cell cytoskeleton: ENERGY METABOLISM OF ERYTHROCYTE
o Spectrin ENERGY REQUIREMENT:
o Ankyrin • The cell requires energy for cell metabolism and to
o Protein 4.1 preserve the membrane integrity
o Actin • Various enzymatic reactions in the cell require energy
• Energy is required to reduce proteins and maintain
Integral Proteins
hemoglobin in its reduced state for proper functioning
• These penetrate the lipid bilayer and are firmly anchored • Two site prone to oxidation are the iron atom in the heme
within it. ring and the sulfhydryl groups on the globin molecule.
o -Band 3 • Oxidation of the normal ferrous state to the ferric state
o -Glycophorins A, B, and C results in methemoglobin which does not deliver oxygen
o -Na+/K+ ATPase • Normally 1% to 3% of oxygen is oxidized to
o -glucose transport protein methemoglobin
o -surface receptors • Oxidation of sulfhydryl groups causes hemoglobin
precipitation (Heinz body formation)
MEMBRANE ENZYME SYSTEM
SOURCES OF ENERGY
1. Sodium Potassium ATPase – Controls transport of EMBDEN-MEYERHOF PATHWAY (EMP)
Sodium and Potassium. • This is an anaerobic process for energy generation
2. Calcium, Magnesium ATPase – calcium pump moves through glucose catabolism to lactate
calcium out of the cell to plasma against a high • About 90% to 95% of glucose used by the cells is
concentration gradient metabolized by the EMP
• ATP is generated during the glycolysis of glucose to
**Additional Notes:
lactate
o Membrane proteins facilitate movement of substrates • ATP is needed to maintain membrane shape and
and cofactors in and out cell deformability
o Examples : include the Na+, K+ - ATPase and Ca2+, Mg2+ o Through phosphorylation of spectrin and
- ATPase calcium chelation
o K - higher conc ine RBCside RBC than in the plasma
+ o Provide energy for active transport of cations
o Na+ - lower conc insid o And to modulate the amount of 2,3 DPG
generated
• There is a net yield of two ATP molecules per molecule of
glucose catabolized
• 2,3 DPG is formed from the Rapoport-Luebering shunt
• Helps modulate O2 transport in the cell

- The peripheral proteins include the  and  spectrin also

called band 1 and 2 and actin
- The proteins form the cytoskeleton of the cell and regulate
membrane shape and deformability
- Their linkage is mediated by protein 4.1
- The principal integral proteins are glycoproteins
designated glycophorin A and band 3
- They span the lipid bilayer.
- Band 3 is an inorganic anion transport channel
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
Hexose Monophosphate Shunt and Glutathione Reduction
Pathway
• Also called the pentose phosphate pathway is an aerobic
method of erythrocyte glycolysis
• Processes about 10% of erythrocyte glucose
• Purpose is to provide reducing potential by generating
reduced nicotinamide adenine dinucleotide phosphate
(NADPH)
• It is an oxidative pathway
**Additional Notes:
• Generates NADPH - reduction of glutathione (eliminates
H2O2 formed in erythrocytes)
• Increases RBC source of NADPH & reduced glutathione
ERYTHROCYTE DESTRUCTION
• As the red cell ages, changes occur that make it
susceptible to destruction
• Alteration in the membrane integrity takes place
• Loss of sialic acid and lipids, decreased ATP and
increased Calcium have been implicated in the aging
process
• At 120 days the erythrocytes are recognized as abnormal
and are removed by phagocytic cell in the RES
• As the cell ages it is depleted of glucose and their surface
area decreases
• The spleen recognizes abnormalities in the cell and
sequester it for removal
Summary of Development and Destruction of Erythrocytes
Formation and Destruction of RBCs
LEUKOPOIESIS
• Production of Leukocytes
• Leukopoiesis is stimulated by interleukins and
• colony-stimulating factors (CSFs)
o Interleukins are numbered (e.g., IL-1, IL-2),
whereas CSFs are named for the WBCs they
stimulate (e.g., granulocyte- CSF stimulates
granulocytes)
• Macrophages and T cells are the most important sources
of cytokines
• Many hematopoietic hormones are used clinically to
stimulate bone marrow
FORMATION OF LEUKOCYTES
All leukocytes originate from hemocytoblasts
• Hemocytoblasts differentiate into myeloid stem cells and
lymphoid stem cells
• Myeloid stem cells become eosinophilic, basophilic and
neutrophilic myeloblasts or monoblasts
• Lymphoid stem cells become lymphoblasts
• The myeloblasts develop into eosinophils, neutrophils,
and basophils
• Monoblasts develop into monocytes
• Lymphoblasts develop into lymphocytes
Myeloid Lineage
Myeloid lineage gives rise to granulocytes, and monocytes (and
macrophages), which are not granulocytes. Diagram does not show
changes in cell and nuclear morphologies. Band stage is not shown
above.
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
GRANULOPOIESIS – Development of Granulocytes • The nuclear chromatin is coarse and slightly clumped.
• Nucleoli or remnants of nucleoli may be present.
• There is an abundant amount of light blue cytoplasm
around the nucleus. Also, there may be a few azurophilic
granules in the cytoplasm.

LYMPHOCYTE

• This is the mature cell of the lymphocytic series and the

only cell form found in the peripheral blood
• Lymphocytes vary greatly in size and may be classified as
small, medium or large. However, size does not determine
age of these cells.
• The cells are easily distorted and often appear in irregular
shapes in stained preparations. The nuclear chromatin is
condensed to form large, discrete almost solid clumps,
with thickening of the nuclear membrane. Nucleoli are
absent. Non specific granules may be observed in the
cytoplasm of these cells.

LYMPHOPOIESIS

• Immunologically competent cells

• Primary lymphoid organs
LYMPHOPOIESIS o Bone marrow
o Thymus
• Lymphocytes are derived from committed stem cells that • Secondary lymphoid organs
originate from pluripotent stem cell. o Lymph nodes
• Early lymphoid cells further differentiates into B & T o Spleen
lymphocytes. o Lymphoid tissues
• Lymphocytes
LYMPHOID LINEAGE o B and T lymphocytes
o NK killer cells
• Lymphoid stem cell gives rise to
T-lymphocyte and B- lymphocyte lineages
• T-cell maturation - thymus
• B-cell maturation - bone marrow
• Plasma cells - present in marrow,
lymphatic tissue, connective tissue

B and T cells are non-phagocytic. B- and

T-cells are morphologically similar, but
functionally different. T-cells are either
“helper” or “cytotoxic”. Natural killer (NK)
cells are derived from T-cells and attack
tumor cells. T- and B-cells exit blood at
sites of high endothelial venules. Thymus
and bone marrow are primary lymphoid
organs.

MONOPOIESIS
LYMPHOCYTIC MATURATION SEQUENCE
• Development of the monocyte
LYMPHOBLAST • Stages in the monocytic development are:
o Monoblast
• Cell is similar to other blast cells. It is round or oval, very
o Promonocyte
large, with a large round to oval reddish-purple nucleus.
o Monocyte
• The nuclear chromatin material is fine and well
distributed but perhaps more coarse than in myeloblasts. MONOCYTIC MATURATION SEQUENCE
• The nucleus contains one or two nucleoli.
• The cytoplasm is bluish and non granular and forms a MONOBLAST
thin rim around the nucleus.
Large with a round or oval nucleus. A nucleolus is present. The
PROLYMPHOCYTE nuclear chromatin material is fine and well-distributed. There is a
thin rim of clark blue cytoplasm around the nucleus. There are no
• The nucleus is round or oval in shape but smaller than granules present in the cytoplasm.
the lymphoblast.
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
PROMONOCYTE Lymphocyte
Smaller than the monoblast with the nucleus being irregularly-
shaped. The nuclear chromatin material is fine and spongy. There • Nucleus is dense, round, oval or
may be a nucleolus or a remnant of the nucleolus present. The slightly indented
cytoplasm is grayish blue and may contain non-specific granules. • B lymphocyte - humoral immunity
(~20-30%)
MONOCYTE • T lymphocyte - cell-mediated
immunity (~60-80%)
• The cell is larger than a neutrophil in the thin portions of a
• Natural killer (NK) cell - cell-mediated
smear.
immunity (~5-10%)
• The shape of monocytes is variable.
• Agranulocyte - lysosomal acid hydrolases
• The nuclei are usually round or kidney-shaped, but may
be deeply indented or have two or more lobes connected TYPES OF LEUKOCYTES
by narrow bands. Blunt pseudopods and digestive
vacuoles may be present. 4,000-11,000 cells/mm 3
• Monocytes are most difficult to identify and to differentiate
from other cells. They are frequently mistaken for Granulocytes
immature neutrophils and large lymphocytes.
• Neutrophils: 40-70%
• The three most characteristic features of the monocytes
• Eosinophils: 1-4%
and the most helpful in diagnosis are the dull grayish-blue
• Basophils <1%
color of the cytoplasm, blunt pseudopods and the brain-
like convolution of the nucleus. Agranulocytes
WHITE BLOOD CELL • Monocytes- 4-8%
Neutrophil • Lymphocytes- 20-45%

**mnemonics**
• 2-5 lobe nucleus
• Primary or secondary granules Proportion of Leukocytes in the circulating blood
- Pink (azurophilic granules)
- Grey-blue granules Never Let Monkeys Eat Bananas
• Life 10 hours
LEUKOCYTES
Precursors:

• Myeloblast <4%
• Pro myelocytes
• Myelocytes
• Metamyelocytes
• Band form (stab form)

Eosinophil
• Coarser & more deeply red staining Distribution - blood and CT (as transient or wandering cells)
granules
• Rarely more than two lobes of nucleus Function - immune protection, movement (cell motility)
• Special role in allergy, inflammation &
parasite infection Diapedesis - movement out of blood into connective tissue; in
post capillary venule (low pressure, thin wall).
Basophil
Chemotaxis - movement directed by homing molecules
• \Occasionally seen
• Dark cytoplasmic granules
• Role in Hypersensitivity response
• Give rise to mast cells

Monocyte

• Larger than lymphocyte

• Oval or indented nucleus
• Monocytes >>>>to macrophage
• Specific function depends on the tissue
type:
• Kupffer, Oestoclast, Microglia, Serosal, Langerhans
Hematology – Lecture
Module 2: Hematopoiesis │ PPT NOTES – Hematopoiesis 1 │ Medical Technology 2022
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.

PLATELETS/ THROMBOCYTES

• Small fragments of
megakaryocytes
• Formation is regulated by
thrombopoietin
• Blue-staining outer region,
purple granules
• Granules contain serotonin,
Ca2+, enzymes, ADP, and
platelet-derived growth factor
(PDGF)

THROMBOPOIESIS: NORMAL CELLULAR MATURATION

Genesis of Platelets 1. CYTOPLASMIC MATURATION

• The stem cell for platelets is the hemocytoblast
• The sequential developmental pathway is as shown:
STAGES IN THROMBOCYTE DEVELOPMENT
MEGAKARYOBLAST
The cell is large, irregularly shaped with a
single or several round or oval nuclei and
with a blue, non granular cytoplasm.
Nucleoli are usually present.
• Immature cell: intensely basophilic (blue) because of high
RNA content. Loss of blue as cell matures.
• Granules may appear as cell matures. 1st granules are
nonspecific. Take on specific characteristics as they
mature.
• Relative amount of cytoplasm increases as cell matures.
2. NUCLEAR MATURATION
• Immature nucleus is round or oval and large in proportion
to rest of cell.
• As cell matures, decreases in size and takes on varying
shapes.
• Nuclear chromatin changes from delicate and fine to
coarse and clumped.
• Staining properties change from reddish purple to bluish
purple.
• Nucleoli gradually disappear.
3. CELLSIZE
• As cell matures, becomes smaller in size.

PROMEGAKARYOCYTE

This cell differs from the megakaryoblast in

that there are bluish granules in the
cytoplasm adjacent to the nucleus. The
nucleus in this second stage of maturation
has usually divided one or more times and
the cell has increased in size.

MEGAKARYOCTE

The cell is very large with relatively large

amounts of cytoplasm, and multiple nuclei.
The cytoplasm contains numerous small,
uniformly distributed granules that are
reddish-blue in color.

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.