SAINT MARY’S UNIVERSITY

SCHOOL OF HEALTH AND NATURAL SCIENCES

MEDICAL LABORATORY SCIENCES DEPARTMENT

HEMATOPOIESIS
 Hematopoiesis
o Continuous, regulated process of blood cell production
o Includes:
 Cell renewal
 Proliferation
 Differentiation
 Maturation

HUMAN STEM CELL -

 Types:
o Totipotential stem cell
 Present in the first few hours after an ovum are fertilized
 Most versatile
 Develop embryo from fetus
o Pluripotential stem cell
 Present several days after fertilization
 Can develop into any cell type
o Multipotential stem cell
 Derived from pluripotent stem cells
 Found in adults, but they are limited to specific types of cells to form tissues

 Stem Cell Theory

o Monophyletic
 Suggests that all blood cells are derived from a single progenitor stem cell called
pluripotent hematopoietic stem cell
 Most widely accepted theory
 Culture-Derived Colony-Forming Units (CFUs)

| HEMATOLOGY 1( L E C T U R E )
 SAINT MARY’S UNIVERSITY
SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

o Polyphyletic
 Suggests that each of the blood cell lineages is derived from its own unique stem cell

HEMATOPOIETIC DEVELOPMENT
 Stages or Phases
o Mesoblastic stage/Yolk sac
 Begins around 19 days of embryonic development after fertilization
 Formation of primitive erythroblast in the central cavity of the yolk sac
 These primitive but transient yolk sac erythroblasts are important in early
embryogenesis to produce hemoglobin needed for delivery of oxygen to rapidly
developing embryonic tissues.
 SAINT MARY’S UNIVERSITY
SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

o Hepatic phase
 Begins at 5th to 7th week of gestation
 Reaches its peak by the 3rd month of fetal development, then gradually declines after the
6th month, retaining minimal activity until 1 to 2 weeks after birth.
 The developing spleen, kidney, thymus, and lymph nodes contribute to the
hematopoietic process during this phase.
 Characterized by recognizable clusters of developing erythroblasts, granulocytes, and
monocytes colonizing the fetal liver, thymus, spleen, placenta, and ultimately the bone
marrow space in the final medullary phase
 Production of megakaryocytes also begins
 Fetal hemoglobin (Hb F) is the most predominant hemoglobin
o Medullary (Myeloid) phase
 Prior to the 5th month of fetal development, hematopoiesis begins in the bone marrow
cavity
 By the end of the 24th week of gestation, the bone marrow becomes the primary site of
hematopoiesis.
 Measurable levels of erythropoietin (EPO), granulocyte colony stimulating factor (G-
CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and hemoglobin F
and A can be detected.

ADULT HEMATOPOIETIC TISSUE

 Located in the bone marrow, lymph nodes, spleen, liver, and thymus
 An ideal environment of HSC allows for: self-renewal, proliferation and differentiation, and apoptosis
 Bone Marrow
o One of the largest organs in the body
o The tissue located within the cavities of the cortical bones
o Types:
 Red marrow: haematopoietically active marrow
 Yellow marrow: haematopoietically inactive marrow
o During early infancy and childhood, all the bones in the body contain primarily red (active)
marrow
o Retrogression: process of replacing the active marrow by adipocytes (yellow marrow) during
development
o Adults: 40% active marrow; 60% inactive marrow
o Stromal cells
 General term for specialized cells within the bone marrow that provide protective
and nourishing environment to the HSCs.
 Includes:
 Monocyte/ Macrophage
 Fibroblast (Reticular cells)
 Adipocytes
 SAINT MARY’S UNIVERSITY
SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

 Endothelial cells
 Lymphocytes
 Osteoblasts
 Osteoclasts
o Normal myeloid to erythroid ratio: 3:1
o Marrow Cellularity
Normocellular Marrow has 30 to 70% HSC
Hypercellular/Hyperplastic Marrow has >70% HSC
Hypocellular/Hypoplastic Marrow has <30% HSC
Aplastic Marrow has decreased or no blood cells

o Normal Marrow Cells

 Macrophages
 Mast cells
 Osteoblast
 Osteoclast
o Bone marrow smear collection and preparation
 Posterior iliac crest
 Sternum
 Anterior iliac crest and spinal/vertebral bodies
 Upper end of tibial bone
o Bone marrow specimen and instruments
 Trephine (Core) biopsy: trephine biopsy needle or Jamshidi needle
 Bone marrow aspirate: aspiration needle or University of Illinois Sternal needle
o Bone marrow smears: Should be retained for 10 years
o Bone marrow differential
 Normal ranges of bone marrow cells in adult
Cell Percentage
Myeloblast 0.3 – 4.0
Promyelocyte 1.0 – 5.0
Myelocyte
 Neutrophil  5.0 – 19.0
 Eosinophil  0.5 – 3.0
 Basophil  0.0 – 0.5
Metamyelocyte/Juvenile 13.0 – 32.0
Neutrophils 7.0 – 25.0
Eosinophils 0.5 – 4.0
Basophils 0.0 – 0.7
Lymphocytes 3.0 – 20.0
Monocytes 0.5 – 3.0
Megakaryocytes 0.1 – 3.0
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SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

Plasma cells 0.1 – 3.0

Reticulum cells 0.1
Pronormoblast 1.0 – 5.0
Basophilic normoblast 7.0 – 32.0
Polychromatic normoblast
Orthochromic normoblast
Mitotic cells 0.0 – 2.0

 Extramedullary hematopoiesis
o Blood cell production outside the bone marrow
o Occurs mainly in the liver and spleen
o Spleen
 Largest lymphoid organ in the body
 Contains about 350 mL blood
 Stores 30% of platelets (1/3 of total platelet)
 Splenic tissues
 White pulp: consists of scattered follicles with germinal centers containing
lymphocytes, macrophages, and dendritic cells
 Marginal zone: surrounds the white pulp and forms a reticular meshwork
containing blood vessels, macrophages, memory B cells, and CD4+ T cells
 Red pulp: cord of billroth, contains specialized macrophages for the removal of
senescent RBCs
o Culling
o Pitting
 Splenomegaly
 Causes:
o Chronic leukemia
o Inherited membrane or enzyme defects in RBCs
o Hemoglobinopathies
o Hodgkin disease
o Thalassemia
o Malaria
o Myeloproliferative disorders
 Hypersplenism
o Enlargement of spleen
o Lead to pancytopenia
o Most common cause: congestive splenomegaly secondary to cirrhosis of
the liver and portal hypertension
o Other causes:
 Thrombosis
 Vascular stenosis
 SAINT MARY’S UNIVERSITY
SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

 Aneurysm of the splenic artery

 Cysts
 Autosplenectomy: necrosis of spleen due to entrapment of sickled RBC
 Asplenia
 Can be caused by either surgical removal or radiation overexposure
 Can also occur in association with malabsorption syndromes
 Hematologic results of asplenia:
o Increased susceptibility to infection
o Acute granulocytosis
o Acute thrombocytosis, with occasional giant platelets
o Chronic and absolute lymphocytosis and monocytosis
o Increased appearance of immature RBCs in the circulation
o Increased amount of circulating RBCs with cytoplasmic inclusions or
abnormal forms
o Liver
 Functions:
 Protein synthesis and degradation
 Coagulation factor synthesis
 Carbohydrate and lipid metabolism
 Drug and toxin clearance
 Iron recycling and storage
 Hemoglobin degradation
 Contains Kupffer cells
o Lymph Nodes
 Outer capsule
 Provide support for the macrophages and lymphocytes
 Paracortex
 Contains predominantly T cells and macrophages
 Medullary cords
 Consist primarily of plasma cells and B cells
 Functions:
 Site of lymphocytes proliferation from germinal centers
 Initiation of the specific immune response to foreign antigens
 Filter particulate matter, debris, and bacteria entering the lymph node via the
lymph
o Thymus
 Populated with lymphoid cells, mesenchymal cells, reticular cells, epithelial cells,
dendritic cells, and macrophages
 Site of T lymphocytes development
 SAINT MARY’S UNIVERSITY
SCHOOL OF HEALTH AND NATURAL SCIENCES
MEDICAL LABORATORY SCIENCES DEPARTMENT

 NOTE:
o Commonly Used CD Markers
CD2, CD3 Lymphoid pan T cells
CD4 Helper/Inducer T cells
CD8 Suppressor/Cytotoxic T cells
CD13 Pan Myeloid
CD11c, CD14 Monocytes
CD19, CD20 Lymphoid pan B cells
CD33 Pan myeloid cells
CD34 Hematopoietic stem cell marker (lymphoid and myeloid precursor)
CD16, CD56 NK cells
CD10 Pre CALLA (Common acute lymphoblastic leukemia) marker

PREPARED BY:

Desiree Joy B. Arquero, RMT

First Semester Instructor
Medical Laboratory Science Department
School of Health and Natural Sciences