Hematopoiesis production and Disorders.pptx

HEMATOPOIESIS
DR.S.SUNDARESAN
TAGORE MEDICAL COLLEGE

Hematopoietic Stem Cells (HSCs):
• Undifferentiated cells with the potential to give rise to all blood cell types.
Two main types:
• Multipotent Progenitor Cells (MPPs): Can differentiate into multiple cell types.
• Hematopoietic Stem Cells Proper: Have the potential to differentiate into any blood cell
type.

Steps in Hematopoiesis:
1. Proliferation (Mitosis):
1. HSCs undergo mitosis to produce more stem cells.
2. Some cells remain as stem cells, while others become committed progenitor cells.
2. Differentiation:
1. Progenitor cells differentiate into specific cell lineages (erythroid, myeloid, lymphoid).
3. Maturation:
1. Cells undergo maturation to become fully functional blood cells.

Regulation:
1. Cytokines and Growth Factors:
1. Various signaling molecules regulate the proliferation and differentiation of hematopoietic cells.
• Some cytokines that regulates haematopoiesis are:
• Granulocyte macrophage-colony stimulating factor (GM-CSF):
• It enhances the myeloid lineage, finally leading to the differentiation of granulocytes and macrophages. Such cytokines are
termed as growth factors.
• These growth factors are needed throughout the process of hematopoiesis functioning in order to activate transcription factors.
• Transcription factor GATA-2:
• It is required for the development of all hematopoietic lineages; in its absence animals die during embryogenesis.
• Transcriptional regulator Bmi-1:
• It is required for the self-renewal of HSCs, and in its absence animals die within 2 months of birth because of the failure to
repopulate their red and white blood.
• .

• Other Examples of cytokines involved in haematopoiesis are:
• Colony-stimulating factors (CSFs)
• Erythropoietin (EPO)
• Thrombopoietin (TPO)
• Granulocyte colony-stimulating factor (G-CSF)
• Monocyte colony-stimulating factor (M-CSF)
• Tumor necrosis factor (TNF)
• Transforming growth factor (TGF)
• Stem cell factor (SCF)
• Leukemia inhibitory factor (LIF)
1. Hormonal Control:
1. Erythropoietin (EPO) regulates erythropoiesis.
2. Thrombopoietin (TPO) regulates thrombopoiesis

• Hematopoietic stem cells (HSCs) are multipotent cells with critical functions in the
maintenance and replenishment of the blood and immune system.
1. Self-Renewal
• HSCs have the ability to undergo self-renewal, meaning they can divide and give rise
to identical daughter cells.
2. Differentiation
• They give rise to committed progenitor cells, which further differentiate into mature
blood cells, including red blood cells, white blood cells, and platelets.
3. Production of Blood Cells
• HSCs are the source of all blood cells, contributing to the continuous production and
replenishment of erythrocytes (red blood cells), leukocytes (white blood cells), and
thrombocytes (platelets).
FUNCTIONS

4. Immune System Support:
• HSCs play a pivotal role in supporting the immune system by generating lymphoid progenitor cells, which
differentiate into T lymphocytes (T cells), B lymphocytes (B cells), and natural killer (NK) cells.
5. Hematopoietic Microenvironment Regulation
• HSCs interact with the bone marrow microenvironment, which includes stromal cells, endothelial cells, and
extracellular matrix components.
6. Response to Environmental Signals:
• HSCs respond to signals from the surrounding environment, including cytokines, growth factors, and
hormones
7. Maintenance of Hematopoietic Homeostasis:
• HSCs contribute to the maintenance of hematopoietic homeostasis by balancing the production of different
blood cell lineages.
• This ensures a proper ratio of red blood cells, white blood cells, and platelets to meet the body's
physiological needs.
8. Adaptation to Physiological Demands:
• HSCs can adjust their activity in response to changing physiological demands, such as during periods of
increased blood cell production in response to injury, infection, or other stressors

Hematopoietic Tissues:
1.Bone Marrow:
1. The primary site for hematopoiesis in adults.
2. Red bone marrow is involved in the production of blood cells.
2.Liver and Spleen (in fetus):
1. These organs are involved in hematopoiesis during embryonic and fetal
development.

• Bone Marrow:
Red Bone Marrow:
• Found in the spongy bone tissue of flat bones (e.g., pelvis, sternum, ribs, skull).
• Primary site for hematopoiesis in adults.
• Composed of hematopoietic stem cells (HSCs), which give rise to all blood cell types.
Yellow Bone Marrow:
• Contains more fat cells and fewer hematopoietic cells.
• Can convert back to red bone marrow in response to increased demand for blood cell production.
Liver (During Embryonic and Fetal Development):
• In the early stages of development, the liver plays a crucial role in hematopoiesis.
• As development progresses, the liver's hematopoietic function decreases, and the bone marrow takes over.
Spleen (During Embryonic and Fetal Development):
• Like the liver, the spleen is involved in hematopoiesis during early development.
• As the bone marrow becomes the primary site for hematopoiesis, the spleen's hematopoietic function
diminishes.

4. Lymphatic Tissues:
• Lymph nodes, tonsils, and other lymphatic tissues may contribute to certain aspects of immune
cell production.
• While not the primary sites, they play a role in the development and maturation of
lymphocytes (a type of white blood cell).
5. Thymus:
• The thymus is involved in the maturation of T-lymphocytes (T cells), an essential component
of the immune system.
• It is not a site for the production of hematopoietic stem cells but is critical for the development
of functional immune cells.
Regulation of Hematopoiesis:
• Hematopoiesis is tightly regulated by various signaling molecules, including cytokines and
growth factors.
• Hormones such as erythropoietin (EPO) and thrombopoietin (TPO) play key roles in the
regulation of specific blood cell lineages.

Types of Blood Cells:
1. Erythropoiesis:
1. Formation of red blood cells (erythrocytes).
2. Controlled by the hormone erythropoietin, which is produced by the kidneys in response to
low oxygen levels.
2. Leukopoiesis:
1. Formation of white blood cells (leukocytes).
2. Differentiation into various types of leukocytes: neutrophils, lymphocytes, monocytes,
eosinophils, and basophils.
3. Thrombopoiesis:
1. Formation of platelets (thrombocytes).
2. Regulated by thrombopoietin.

• Myeloid cells: It consists of-
• Monocytes
• Eosinophils
• Basophils
• Neutrophils
• Macrophages
• Erythrocytes
• Megakaryocytes
• Platelets.
• Lymphoid cells: It consists of-
• B cells
• T cells
• Natural killer cells
• Innate lymphoid cells.

Hematopoietic Stem Cell (HSC):
• Size: Variable
• Shape: Undifferentiated, round
• Color: N/A
• Mechanism: HSCs are pluripotent stem cells capable of differentiating into various blood cell types.
• Time: A few days.
Proerythroblast:
• Size: Large (12-20 μm)
• Shape: Round
• Color: Blue-purple cytoplasm (basophilic)
• Mechanism: Initiates synthesis of hemoglobin.
• Time: About 1-2 days.
Basophilic Erythroblast:
• Size: Slightly smaller than proerythroblasts
• Shape: Round
• Color: Basophilic cytoplasm due to ongoing hemoglobin synthesis
• Mechanism: Continued hemoglobin synthesis; nucleus begins to condense.

Polychromatic Erythroblast:
• Size: Further reduced
• Shape: Round
• Color: Pinkish cytoplasm (polychromatic) due to increased hemoglobin
• Mechanism: Intense hemoglobin synthesis; further nuclear condensation.
• Time: About 1 day.
Orthochromatic Erythroblast:
• Size: Smaller than previous stages
• Shape: Round
• Color: Cytoplasm becomes even more eosinophilic (orthochromatic) as hemoglobin synthesis peaks
• Mechanism: Final nuclear condensation and extrusion of the nucleus.
• Time: About 1 day.
.

Reticulocyte:
• Size: Slightly larger than mature RBCs
• Shape: Slight central pallor; biconcave shape
• Color: Bluish-gray tint due to residual ribosomal RNA
• Mechanism: Nucleus is expelled; the cell enters the bloodstream; ribosomal remnants visible under certain
stains.
• Time: 1-2 days in the bone marrow before entering circulation
Mature Erythrocyte (Red Blood Cell):
• Size: 7-8 μm in diameter
• Shape: Biconcave disc
• Color: Red (due to hemoglobin)
• Mechanism: No nucleus or organelles; flexible biconcave shape facilitates gas exchange; primary
function is oxygen transport.
• Time: Lifespan in circulation is about 120 days.
Regulation by Erythropoietin (EPO):
• Mechanism: EPO, produced in response to low oxygen levels, stimulates the differentiation,
proliferation, and survival of erythroid progenitor cells.

GRANULOPOIESIS (DEVELOPMENT OF
GRANULOCYTES):
Myeloblast:
• Size: Larger than mature granulocytes
• Shape: Round or oval
• Mechanism: Initiates synthesis of specific granules.
Promyelocyte:
• Size: Slightly smaller than myeloblasts
• Color: Cytoplasm becomes more distinct; specific granules develop.
• Mechanism: Continued granule synthesis.

Myelocyte:
1. Size: Smaller than promyelocytes
2. Shape: Round or slightly indented
3. Color: Specific granules are prominent, and cytoplasm takes on a distinct color.
4. Mechanism: Granules mature; nucleus undergoes changes.
Metamyelocyte:
1. Size: Further reduced
2. Shape: Kidney-shaped nucleus
3. Color: Distinctive cytoplasmic coloration
4. Mechanism: Nucleus continues to change shape; cell prepares for final stages of maturation.
Band Neutrophil:
• Size: Slightly smaller than mature neutrophils
• Shape: Nucleus is horseshoe or band-shaped
• Color: Distinctive cytoplasmic coloration
• Mechanism: Nucleus becomes elongated and horseshoe-shaped.

Segmented Neutrophil (Mature Neutrophil):
• Size: 10-12 μm
• Shape: Segmented nucleus; multi-lobed
• Color: Distinctive cytoplasmic coloration
• Mechanism: Final maturation; ready for immune response.
• Time: Several days to a week.

• b. Eosinophil Development:
1. Myeloblast to Metamyelocyte:
1. Similar stages as neutrophils.
2. Mechanism: Synthesis of specific granules containing enzymes.
2. Mature Eosinophil:
1. Size: 12-17 μm
2. Shape: Bilobed nucleus; often bi-lobed or tri-lobed.
3. Color: Eosinophilic granules give a reddish-orange color.
4. Mechanism: Granules contain enzymes involved in combating parasitic infections.
5. Time: About 2 weeks.

• c. Basophil Development:
1. Myeloblast to Metamyelocyte:
1. Similar stages as neutrophils.
2. Mechanism: Synthesis of specific granules containing histamine and other mediators.
2. Mature Basophil:
1. Size: 12-15 μm
2. Shape: Bilobed nucleus; may be obscured by granules.
3. Color: Dark purple or blue due to large basophilic granules.
4. Mechanism: Granules release histamine and other inflammatory mediators.
5. Time: Variable.

Monopoiesis (Development of Monocytes):
a. Monoblast:
• Size: Larger than mature monocytes
• Mechanism: Initiates synthesis of specific granules.
b. Promonocyte:
• Size: Slightly smaller than monoblasts
• Color: Cytoplasm becomes more distinct; specific granules develop.
• Mechanism: Continued granule synthesis.
c. Monocyte:
• Size: Larger than neutrophils
• Shape: Kidney-shaped or amoeboid nucleus
• Color: Abundant pale blue-gray cytoplasm
• Mechanism: Final maturation; migrates into tissues to become macrophages or dendritic cells.
• Time: A few days.

a. Lymphoblast:
• Size: Variable
• Shape: Round
• Mechanism: Initiates synthesis of specific proteins.
b. Prolymphocyte:
• Size: Slightly smaller than lymphoblasts
• Shape: Round
• Color: Cytoplasm becomes more distinct.
• Mechanism: Continued differentiation and maturation.
c. Mature Lymphocyte (T Cell, B Cell, NK Cell):
• Size: Variable (small to medium-sized)
• Shape: Round or irregular
• Color: Scant cytoplasm, may be pale or basophilic.
• Mechanism: Specific functions depending on the type (e.g., T cells, B cells, NK cells).
• Time: Variable, can range from days to weeks.

• Erythropoiesis:
• The process of formation of red blood cells termed as erythrocytes is known as erythropoiesis.
• It is enhanced by decreased levels of oxygen in the blood, which signals for the secretion of
• Erythropoietin is a hormone central to the formation of red blood cells.
• Erythropoiesis takes on average 2 days to be completed from to form mature red blood cell from
• 2 million erythrocytes are produced every second in our bodies.
• Hematopoietic cells determined to become red blood cells usually get smaller and more condensed as
their nuclei.
• The unipotential cell becomes proerythroblast, which has uncondensed nucleus and has basophilic or
• Then the cell becomes a basophilic erythroblast, which is followed by a polychromatophilic erythroblast
• In polychromatophilic erythroblast stage, the nucleus becomes more condensed than the latter two
• In the succeeding orthochromatophilic erythroblast stage, the nucleus is much smaller than that of the
cytoplasm.
• Then comes the reticulocyte stage, where the red blood cell lacks nucleus, but still stains somewhat blue
polyribosomes within the cell.
• Ultimately, the erythrocyte is the mature red blood cell, with no nucleus and no polyribosome remnants

• Granulopoiesis
• The process of formation of granulocytes is termed as granulopoiesis.
• Granulocytes are white blood cells having multi-lobular nuclei and cytoplasmic granules.
• The unipotential hematopoietic cell which forms a myeloblast is large.
• It has a cytoplasm that stains blue with a large nucleus.
• This cell gives rise into a promyelocyte that contains azurophilic granules. Then it becomes a myelocyte,
which has a non-indented still rather large nucleus.
• This cell then gives rise to a metamyelocyte, which is alike in size to a mature granulocyte and the nucleus
starts to become indented.
• After this stage is the band cell stage, where the nucleus resembles a horseshoe and has definitive
indentation.
• Ultimately, there is the mature granulocytes having a lobed nucleus and cytoplasmic granules.
• The entire process occurs over a period of 2 weeks.

• Monopoiesis:
• The process by which monocytes are formed is termed as monopoiesis.
• The monoblast is the committed progenitor cell, found only in the bone marrow. Also, monoblast has
a basophilic cytoplasm without granules.
• These monoblasts give rise to promonocytes, which are smaller in size with nuclei that become
slightly indented, before becoming monocytes.
• Monocytes have kidney-shaped nuclei and can develop into dendritic cells or macrophages.

• Lymphopoiesis:
• The formation of lymphocytes, starts from their first committed progenitor cells, lymphoblasts, this
process is called Lymphopoiesis.
• These cells after maturation, are able to differentiate into either B, T or natural killer cells.
• Thrombopoiesis:
• Megakaryocytes, which are extremely large cells within the bone marrow forms the platelets, this
process is termed as thrombopoiesis.
• When the plasma membranes of megakaryocytes are fragmented, the origin of individual platelets
take place, thus generating platelets containing many granules.

Disorders of Hematopoiesis:
Anemia:
• Iron-deficiency anemia
• Vitamin B12 deficiency anemia (pernicious anemia)
• Folate deficiency anemia
• Sickle cell anemia
• Thalassemia
• Hemolytic anemia (e.g., autoimmune hemolytic anemia, hereditary spherocytosis)
• Aplastic anemia
• Anemia of chronic disease

Leukopenia:
1. Neutropenia
2. Lymphopenia
3. Monocytopenia
4. Eosinopenia
5. Basopenia
Thrombocytopenia:
1. Immune thrombocytopenic purpura (ITP)
2. Thrombotic thrombocytopenic purpura (TTP)
3. Drug-induced thrombocytopenia
4. Heparin-induced thrombocytopenia (HIT)
5. Hypersplenism
6. Disseminated intravascular coagulation (DIC)
7. Congenital thrombocytopenia syndromes

Myelodysplastic Syndromes (MDS):
1. Refractory anemia
2. Refractory cytopenia with multilineage dysplasia
3. Refractory anemia with excess blasts
4. Refractory cytopenia with multilineage dysplasia and ring sideroblasts
5. Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
Myeloproliferative Neoplasms (MPNs):
1. Polycythemia vera
2. Essential thrombocythemia
3. Primary myelofibrosis
4. Chronic myeloid leukemia (CML)
5. Chronic neutrophilic leukemia
6. Chronic eosinophilic leukemia
7. Mast cell disease

Bone Marrow Failure Syndromes:
1. Aplastic anemia
2. Diamond-Blackfan anemia
3. Fanconi anemia
4. Shwachman-Diamond syndrome
5. Dyskeratosis congenita
6. Paroxysmal nocturnal hemoglobinuria (PNH)
Hemophagocytic Lymphohistiocytosis (HLH):
1. Primary HLH
2. Secondary HLH (e.g., infection-associated HLH, malignancy-associated HLH)

Hemoglobinopathies:
1. Sickle cell disease
2. Thalassemia
Erythrocytosis:
1. Secondary erythrocytosis (e.g., due to chronic hypoxia, renal disease)
2. Polycythemia vera
Pure Red Cell Aplasia:
• Acquired pure red cell aplasia
• Diamond-Blackfan anemia (a congenital form of pure red cell aplasia)

Paroxysmal Nocturnal Hemoglobinuria (PNH):
• Acquired hemolytic anemia
Congenital Disorders of Hematopoiesis:
• Congenital neutropenia syndromes
• Congenital thrombocytopenia syndromes
• Congenital amegakaryocytic thrombocytopenia
• Congenital dyserythropoietic anemias
• Congenital sideroblastic anemia
Marrow Infiltrative Disorders:
• Leukemia
• Lymphoma
• Metastatic cancer
• Myeloma
• Gaucher disease

Hematopoiesis production and Disorders.pptx

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