Lecture-8 Granulopoiesis and Its Regulation

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MYELOPOIESIS / GRANULOPOIESIS

AND ITS REGULATION


Awal Mir Khattak
Demonstrator MLT

B.Sc. MLT Baqai Medical University Karachi


M.Sc. Hematology Baqai Medical University Karachi
M.Phil. Medical Lab Sciences, The University of Haripur
DEFINITION

Granulopoiesis/Myelopoiesis

It is the process of proliferation,


differentiation and maturation of granulocytes
in the bone marrow
GRANULOPOIESIS

• Granulocytes arise from pluripotent hematopoietic stem


cells.
• PHSC differentiate into granulocyte-monocyte colony
forming unit (GM-CFU). This further differentiated into
granulocyte colony forming unit (G-CFU).
• G-CFU pass through successive divisions and stages and
ultimately form mature granulocytes.
STAGES OF GRANULOPOIESIS
• Proliferation and maturation of myeloid series in the bone
marrow demonstrates a continuum of development from
myeloblast to the most mature granulocytes.
• Each granulocytes follow the same pattern of development
i.e. myeloblast, promyelocyte, myelocyte, metamyelocyte,
band cell and mature granulocytes.
• Each granulocyte can be distinguished at myelocyte stage
due to the appearance of specific granules.
STAGES OF GRANULOPOIESIS

• During maturation, there is reduction in nucleus volume,


condensation of chromatin, change in nuclear shape,
appearance and disappearance of primary granules,
appearance of secondary granules, color changes and
change in size of the cell.
• Myeloblast, promyelocyte and myelocyte; these cells
undergo mitosis and have the capability of division.
STAGES OF GRANULOPOIESIS
• Metamyelocytes and band cells are the components of
maturation pool. These cells do not divide.
• Segmented neutrophils stored in the bone marrow and are
released in the circulation.
• After few hours neutrophils marginate along with the vessel
wall and is termed as marginating pool. These cells leave the
circulation and enter the tissues passing through the
endothelial cells by a process known as diapedesis.
STAGES OF GRANULOPOIESIS
STAGES OF GRANULOPOIESIS
• Morphologically Granulopoiesis is divided into 6 stages

1. Myeloblast

2. Promyelocyte

3. Myelocyte

4. Metamyelocyte

5. Band cells / stab cell

6. Mature granulocytes (Neutrophils, eosinophils, basophils)


STAGES OF GRANULOPOIESIS
1. Myeloblast (0.2-1.5%)
Size: Large (14-20 um), Shape: Round to oval, N:C: High (4:1)
Cytoplasm:
Color: Light blue
Amount: Scanty
Granule: Primary granules present
Granule color: Reddish Purple
Nucleus:
Color: Radish purple
Shape: Round to oval
Chromatin Pattern: Open
Nucleolus: 2-4 present
STAGES OF GRANULOPOIESIS
1. Promyelocyte (2-4)
Size: Large (15-21 um), Shape: Round to oval, N:C: High
Cytoplasm:
Color: Basophilic
Amount: Moderate
Granule: Primary granules present
Granule color: Reddish Purple
Nucleus:
Color: Radish purple
Shape: Round to oval
Chromatin Pattern: Coarse
Nucleolus: May be present
STAGES OF GRANULOPOIESIS
1. Myelocyte (8-16)
Size: Large (12-18 um), Shape: Round to oval, N:C: (50:50)
Cytoplasm:
Color: Light Blue
Amount: abundant
Granule: Primary + appearance of secondary granules
Granule color: Pink
Nucleus:
Color: Radish purple
Shape: Round to oval
Chromatin Pattern: Coarse
Nucleolus: Absent
STAGES OF GRANULOPOIESIS
1. Metamyelocyte (9-25)
Size: Large (10-18 um), Shape: Round to oval, N:C: (decrease)
Cytoplasm:
Color: Pinkish
Amount: abundant
Granule: Primary+secondary granules
Granule color: Pinkish
Nucleus:
Color: Dark purple
Shape: Kidney/horse-shoe shaped
Chromatin Pattern: Condensed
Nucleolus: Absent
STAGES OF GRANULOPOIESIS
1. Band Cell (9-15)
Size: Large (10-18 um), Shape: Round to oval, N:C: (decrease)
Cytoplasm:
Color: Pinkish
Amount: abundant
Granule: Primary + secondary granules
Granule color: Pinkish
Nucleus:
Color: Dark purple
Shape: Horse-shoe shaped
Chromatin Pattern: Condensed
Nucleolus: Absent
STAGES OF GRANULOPOIESIS
1. Segmented Neutrophil
Size: Large (10-18 um), Shape: Round to oval, N:C: (decrease)
Cytoplasm:
Color: Pink
Amount: Bbundant
Granule: Primary + secondary granules
Granule color: Pinkish
Nucleus:
Color: Dark purple
Shape: Segmented/multi lobes (2-5)
Chromatin Pattern: Condensed
Nucleolus: Absent
Regulation of Granulopoiesis
• Growth factors essential for the proliferation, growth,
development and maturation of granulocytes include
granulocyte-monocyte colony stimulating factor (GM-
CSF), granulocyte colony stimulating factor (G-CSF),
interleukin-6 (IL-6), IL-11, IL-1, IL-3 and IL-5.
• Increased granulocyte and monocyte production in
response to an infection is induced by increased
production of growth factors from stromal cells and T
lymphocytes, stimulated by endotoxin, and cytokines
such as IL‐1 or tumor necrosis factor (TNF)
Regulation of Granulopoiesis
Regulation of Granulopoiesis
CLINICAL APPLICATION OF G-CSF
• G‐CSF is used as a therapeutically and administrated
intravenous or subcutaneous that increased neutrophils
count. Short‐acting G‐CSF is given daily. A longer‐acting G‐
CSF can be given once in 7–14 days.
• Indications:
• Post‐chemotherapy/radiotherapy
• Stem cell transplantation,
• Myelodysplasia
• Aplastic anemia,
• Severe benign neutropenia,
• Peripheral blood stem cell mobilisation

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