HEMATOPOIESIS  Aorta – gonad mesonephros region - the

mesodermally derived intraembryonic region.

- A continuous, regulated process of blood cell
 Paraaortic splanchnopleure – earlier
production that include cell renewal, proliferation,
development stage. It produces potent HCSs
differentiation, and maturation.
and multipotential progenitor cells before
- These process results in the formation
their appearance in the yolk sac.
development, and specialization of all of the
functional blood cells that are released from the
bone marrow to the circulation.
MESOBLASTIC PHASE
- HEMATOPOIESIS is considered to begin around the
- Hematopoietic system serves as a functional
nineteenth day of embryonic development after
model to study stem cell biology, proliferation,
fertilization.
maturation and their contribution to disease and
- Cells from mesoderm migrate to the yolk sac
tissue repair.
- Form primitive erythroblast in the central cavity of
- RBC life span: 120 days
the yolk sac. (FORMED DUIRNG THE FIRST 2 TO 8
- Hematopoietic system is capable of self-renewal
WEEKS OF LIFE)
(replenishment) and differentiation into all
- Produces hemoglobin (Gower 1, Gower 2, and
required cell lineages.
Portlnd) needed for delivery of oxygen to rapidly
- Fetal development
developing embryonic tissues.
 Initiates in the yolk sac
- AGM region is the only site of definitive
 Progresses in the aorta-gonad mesonephros
hematopoiesis during embryonic development
(AGM) region (mesoblastic phase)
- Metcalf and Moore performed culture
 The to the fetal liver (hepatic stage)
expirementsusinf n7.5 – day mouse
 Resides in the bone marrow (medullary
- Yolk sac – major site of adult blood formation in
phase)
the embryo.
- Blood islands remain active 8-12 weeks
Hematopoietic system consists of:
- Blood cell formed: ERYTHROBLAST (1ST BLOOD
 Bone marrow CELLS)
 Liver
 Spleen HEPATIC PHASE
- Begins at 5 to 7 gestational weeks
 Lymph nodes
- LIVER – major site of hematopoiesis during the 2 nd
 Thymus
trimester of fetal life.
ORIGIN OF BLOOD CELLS - Hematopoiesis in the fetal liver reaches its peak
by the third month of fetal development then
Hematopoietic stem cells (HSCs) are the foundation of gradually declines after sixth month, retaining
the adult hematopoietic system. minimal activity until 1 – 2 weeks after birth.
- Gives rise to fetal Hgb (4th month)
- Thymus – first develop organ in the fetus, becomes
Types of human cells
the major site of T cell production
1. Totipotential stem cells – present in the first
- Kidney and spleen – produce B cells
few hours after ovum is fertilized. It is the
- Granulocytes and Megakaryocytes – 3rd month
most versatile type of stem cell
- Lymphocytes – 4th month
2. Pluripotential stem cells – present several days
- Monocytes – 5th month
after fertilization
3. Multipotential stem cell – derived from
pluripotential stem cells. Found in adults, but
MEDULLARY PHASE
- Prior to the fifth/fourth month of fetal
they are limited to specific types of cells to
development
form tissues.
- BONE MARROW
Ex: bone marrow stem cells – produce all types of blood - After 5th fetal month = primary site of
cells, bone cartilage and adipose (fat) cells. hematopoiesis
- At birth, BONE MARROW becomes the ONLY SITE
Early development of Blood cells FOR PRODUCTION
- Originate from the mesenchymal tissue that arises - In adult, the principal source is the STERNUM and
from the embryonic germ layer, the mesoderm. other flat bones
- STEM CELLS: pluripotential/mutipotential
  Retain the ability to differentiate into ay cell of the arteries, veins, and vascular
line sinuses
 CFU- spleen  regulate the flow of particles entering
- Progenitor / committed cells and leaving hematopoietic spaces in the
 Unipotential cell lines vascular sinuses
- Precursor cells  Adipocytes
 Blast forms  are large cells with a single fat vacuole
 they play a role in regulating the volume
Bone marrow site and functions of the marrow in which active
 Yellow marrow – inactive and composed hematopoiesis occurs
mostly of fat (adipose) tissue  Macrophage
 Red marrow – normally active in the  function in phagocytosis, and both
production of most types of leukocytes, macrophages and lymphocytes secrete
erythrocytes, and thrombocytes various cytokines that regulate
- At birth – dominated by red marrow hematopoiesis
- By age of 18 – red marrow is found only in the  they are located throughout the marrow
vertebrae, ribs, sternum, skull bones, pelvis, and to space
some extent the proximal epiphyses of the femur  Osteoblasts
and humerus  bone-forming cells
- Bone marrow – is the largest organs in the body, is  Osteoclast
the tissue located within the cavities of the cortical  bone - resorbing cells
bones.  Reticular adventitial cells
- Calcified bone – trabeculae, radiate out from from  form an incomplete layer of cells on the
the bone cortex into the central space, forming a abluminal surface of the vascular sinuses
three-dimensional matrix resembling honeycomb
- Retrogression – the process of replacing the active EXTRAMEDULLARY
marrow by adipocytes (yellow marrow) during HEMATOPOIESIS
development
- Bone marrow consist: - Abnormal circumstances, the spleen, liver, and
 Hematopoietic cell lymph nodes revert back to producing immature
 Blood vessels blood cells
 Stroma cells 1. When the bone marrow becomes dysfunctional in
 Fat (adipose) tissue cases such as aplastic anemia, infiltration by
 Osteoblast and osteoclast malignant cells, or over proliferation of a cell line
 Macrophages (e.g., leukemia).
 Lymphocytes 2. When the bone marrow is unable to meet the
 Endothelial cells demands placed on it, as in the hemolytic anemia
 Reticular adventitial cells (fibroblast)
 Erythroblast – develop in small clusters, and Organs Pathophysiology
more mature forms. Located adjacent to the Liver - Involved blood
outer surface of the vascular sinuses.  Major site of related disease
 Megakaryocytes – located adjacent to the blood cell - The liver can
production maintain
walls of the vascular sinuses
during the hematopoietic
 Immature Myeloid (granulocytic) cells – second stem and
through the metamyelocytes stage are located trimester of progenitor cells to
deep within the cords. fetal produce various
development blood cells (called
.
Hematopoietic microenvironment Kupffer cells
extramedullary
- Hematopoietic inductive microenvironment, or hematopoiesis) as
 Lumen of the
niche plays an important role in nurturing and response to
sinusoids
infectious agent or
protecting HSCs and regulating a balance among  Maintain
in pathologic
their quiescence, self-renewal, and differentiation. contact with
the myelofibrosis of
 Endothelial cells the marrow.
endothelial
 broad, flat cells that form a single cells and
continuous layer along the inner surface foreign
 debris  Mature cells – the most develop group with
 Secrete specific functions
mediators  Hematopoietic progenitor cells can be derived
that regulate into two major types
protein
synthesis in  Noncommitted or undifferentiated
the hematopoietic stem cells
hepatocytes  Committed progenitor cells
Spleen 2 routes:  Two major ancestral cell lines
 Largest lymphoid  Slow-transit  Lymphocytic cells – precursor of either
organ in the body. pathways
Three types of solenic mature B and T cells
 Rapid-transit
tissues: pathways  Nonlymphocytic cells – progresses the
 White pulp Hypersplenism progenitor colony – forming unit,
 Red pulp  Enlargement granulocyte – erythrocyte monocyte –
 Marginal zone of the spleen megakaryocytes (CFU-GEMM)
resulting in
some degree
of
Lineage specific hematopoiesis
pancytopenia
despite the  Erythropoiesis occurs in distinct anatomical
presence of sites called erythropoietic islands, specialized
hyperactive niches in which erythroid precursors
bone marrow. proliferate, differentiate, and enucleate.
Lymph nodes Increased number of  Granulopoiesis can be recognized as a
 Located along microorganisms enters
maturational unit. Maturing cells spend an
lymphatic the nodes,
capillaries average of 3 to 6 days in the proliferating pool.
overwhelming the
Lymph nodes divided into: macrophages and average life span of 6 to 10 hours in circulation
 Outer region – causing adenitis.  Lymphocytes and plasma cells are produced in
cortex lymphoid follicles
 Inner region -
 Megakaryopoiesis takes place adjacent to the
medulla
Thymus sinus endothelium. Develop into platelets in
 Originates from approximately 5 days.
endodermal and
mesenchymal Other cells found in Bone marrow
tissue

 Marrow stromal cells

 Mast cells – abundant blue-purple granules
CELLULAR ELEMENTS OF BONE
 Macrophages
MARROW  Bone cells – bone matrix – synthesizing cells
- Progenitor Blood cells - stem cell carry out the
 Osteoblast – resemble plasma cells
ultimate burden of generating multilineage
 Osteoclast – resemble megakaryocytes
mature blood cells over the lifetime of the
organisms.
 Multipotential hematopoietic stem cell
 Progenitor of all blood cells INTERLEUKINS
- cytokines that act independently or in
Stem cell plasticity – able to generate the assortment of
conjunction with other interleukins to
seemingly unrelated types of cells
encourage hematopoietic growth
- used as signaling molecules in many cells of
Phase of hematopoietic cells the body
- first described as signals for communication
 Primitive, multipotential cells – the most
between white blood cells
immature group capable of self-renewal
- primary messengers and directors of the
 Intermediate cells – committed progenitor
immune system
cells destined to develop into distinct cell
lines

General Nuclear Characteristics
Hematopoietic Growth factors
- regulating the proliferation and
Cytoplasmic Characteristics
differentiation of HPCs as well as
regulating the survival and function of
mature blood cells
- encoded by a single gene. ▪
erythropoietin - chromosome 7
- GM-CSF, IL-3, and M-CSF - long arm of
chromosome 5.
- G-CSF - Chromosome 17
Examples of various factor and the target cells
 G-CSF and GM-CSF predominantly affect
myeloid cells
 IL-7 stimulates T and B lymphocytes
 IL-12 targets natural killer cells
Examination of maturing blood cells
General Cellular Characteristics
o Overall cell size
 Size decreases as AGE/MATURITY
increases
o Nuclear-cytoplasmic ratio
 Nuclear size decreases as AGE/MATURITY
increases
 NC ratio decreases as AGE/MATURITY
increases
o Chromatin pattern
 Loose >>> Clumped
o Nuclear shape
 Very distinctive for particular cell types
o Presence of nucleoli
 As cell mature, nucleoli are usually not
visible
o Staining color and intensity
 Darker blue >>> lighter blue
o Granulation
 None >> non-specific >>> specific
o Shape
 Most distinctive variation in cytoplasmic
shape occurs in some blast forms,
monocytes, and megakaryocytes
o Quantity of cytoplasm
 Cytoplasm increases as age increase
o Vacuolization
 Vacuoles increases as age increase
 Artifacts produce id blood is stored for a
longer-than-acceptable period
o Inclusion bodies