HEMOPOIESIS
HEMOPOIESIS
Hemopoiesis - the formation of blood cells in the living body .
Also referred to as hematogenesis,hematopoiesis.
• FETAL LIFE:
• YOLK SAC
• LIVER + SPLEEN
• BONE MARROW 5 TO 7 MONTHS
• ADULT:
• AXIAL SKELETON
BLOOD FORMATION
• EMBRYONIC VISCERAL MESODERM ANGIOBLASTIC
TISSUE BLOOD CELLS 3rd week of IUL
• 1st TRIMESTER - YOLK SAC
• 2nd TRIMESTER - LIVER AND SPLEEN
• 3rd TRIMESTER – CENTRAL + PERIPHERAL SKELETON
• ADULT - AXIAL SKELETON
• “ Hematopoiesis expands to fetal sites in times of
hematological stress.”
HEMOPOIESIS 4
• Blood cells in the adult: formed in red bone marrow
• red cells
• granulocytes
• monocytes
• platelets
• Lymphocytes formed in the red bone marrow, and in the
lymphatic tissues
• The bone marrow consists of two
compartments:
(1) the marrow stromal compartment and
(2) the hematopoietic cell compartment.
The marrow stromal compartment is a
framework of adipose cells, fibroblasts, stromal
cells, vascular endothelial is a framework of
adipose cells, fibroblasts, stromal cells, vascular
endothelial cells, macrophages, and blood
vessels interspersed within trabecular bone
BONE MARROW SINUSOIDS
• LINED BY FLAT ENDOTHELIAL CELLS
• DISCONTINUOUS BASEMENT MEMBRANE
• IN SOME AREAS ONLY THIN CELL
MEMBRANES OF ENDOTHELIAL CELLS
EXIST
• SERVE AS BINDING SITES FOR YOUNG
CELLS BEFORE ENTERING INTO
CIRCULATION
SINUSOID SUPPORT CELLS
• FIBROBLAST COVER 50% OF THE OUTER
SURFACE OF SINUSOID
• SECRETE
• RETICULIN FIBERS
• FORM A MESHWORK TO SUPPORT CELLS
• ECM
• GROWTH FACTORS
• TRANSFORM INTO ADIPOCYTES
• MACROPHAGES STORE IRON
Blood Cell Lifelines 13
• RBC:
• 7-8 days maturation in marrow
• 120 days in circulation
• Lymphocyte T cell:
• 2-3 days maturation in marrow
• Days to decades in circulation
• Monocytes:
• 2-3 days maturation in marrow
• Most 16 hours; some years in circulation
Blood Cell Lifelines cont. 14
• Neutrophils:
• About 2 weeks maturation in marrow
• 6-8 hours in circulation
• Eosinophils:
• About 2 weeks maturation in marrow
• 8-12 hours in circulation
• Basophils:
• About 2 weeks maturation in marrow
• 9-18 months in circulation
• Platelets:
• 5 days maturation in marrow
• 10 days in circulation
Hemopoiesis 15
• HSCs differentiation to lineage - restricted progenitor cells
• Is dependent on the presence of surface receptors on
progenitor cells
• Surface receptors interact with specific cytokines and
growth factors, including CSFs
• Proliferation and maturation then occurs into a specific
lineage
Hemopoiesis 17
Development of erythrocytes (Erythropoiesis)
- CMP cells become MEP cells under the influence of
ERYTHROPOIETIN, IL-3 and IL-4
-
Erythropoiesis
• Proerythroblast
• Basophilic erythroblast
• Polychromatophilic erythroblast
• Orthochromatophilic erythroblast
(normoblast)
• Polychromatophilic erythrocyte
(reticulocyte)
• Mature RBC
(erythrocyte)
Proerythroblasts .
BASOPHILIC ERYTHROBLAST
POLYCHROMATOPHILIC ERYTHROBLAST
• POLYCHROMATOPHILIC
ERYTHROBLAST
- cytoplasm displays
eosinophilia and basophilia
- overall gray or lilac color to
cytoplasm
- distinct pink and purple
regions may also be noted in
cytoplasm
- nucleus smaller than in
basophilic erythroblast
- heterochromatin forms
checkerboard pattern
• helps identify this
stage
• ORTHOCHROMATOPHILIC
ERYTHROBLAST
- small compact densely
stained nucleus
- cytoplasm is acidophilic
• due to large amount of hemoglobin
- is only slightly larger than
mature RBC
- cannot divide at this stage NORMOBLAST
• aka: NORMOBLAST RBC
• Orthochromatophilic erythroblast
then extrudes its nucleus
- ready to pass into blood
sinusoids of red bone marrow
- retains some polyribosomes
to synthesize hemoglobin
- polyribosomes impart a slight
basophilia to the eosinophilic
cytoplasm
- now called polychromatophilic
erythrocyte
• Special staining of the
polychromatophilic
erythrocyte reveals a reticular
network of the polyribosomes
• The cells are therefore also
known as RETICULOCYTES
• In normal blood reticulocytes
make up 1-2% of the total RBC
count
• any increase in this
percentage of reticulocytes
(reticulocytosis) could RETICULOCYTES in peripheral blood
therefore indicate blood loss
Mature erythrocytes and a
few platelets
Kinetics of Erythropoiesis
• Mitoses occur in
• proerythroblasts
• basophilic erythroblasts
• polychromatophilic erythroblasts
• At each of the above stages the erythroblast divides several
times
• Approx 1 week required for the progeny of a basophilic
erythroblast to reach bloodstream
• RBCs are released into circulation soon after being formed
• RBCs are not stored in the bone marrow
Kinetics of Erythropoiesis
• RBC formation and
release controlled by the
glycoprotein hormone
ERYTHROPOIETIN
- synthesized and
secreted by kidney
- responds to ↓ levels
of O2 in the blood
- acts on specific
surface receptors of ErP
Kinetics of Erythropoiesis
• RBCs have life span of 120 days
• At 4 months of age RBCs become senescent (old)
• Macrophage system of spleen, liver and bone
marrow
- phagocytosis and degredation of
senescent RBCs
Hemoglobin breakdown
• Hemoglobin heme and globin.
• Globin amino acids which are reused
• Heme releases Fe, which enters Fe storage pool in the spleen as
hemosiderin or ferritin, which is reused for Hb synthesis
• Heme is also degraded to bilirubin
• Bilirubin binds to albumin and travels to the liver via the blood
• In the liver
• - bilirubin is conjugated
• with glucuronic acid
• - excretion occurs in
• the bile as bilirubin
• diglucuronide
Hemoglobin breakdown
DEVELOPMENT OF THROMBOCYTES
(Thrombopoiesis)
• MEP megakaryocyte committed progenitor
(MKP) cell megakaryoblast
• Successsive endomitoses under stimultion by
thrombopoietin results in a megakaryocyte
platelets
Hemopoiesis
Thrombopoiesis 36
• On TEM note
peripheral
cytoplasm of
megakaryocyte
with
platelet
demarcation
channels
Hemopoiesis
Thrombopoiesis
• Note more platelet
demarcation
channels
Thrombopoiesis
• Note:
• megakaryocyte
(arrow) in bone
marrow forming
platelets
Hemopoiesis
Development of Granulocytes
(Granulopoiesis) 39
• From the neutrophil,
eosinophil and basophil
progenitor cells
• 5/6 morphological stages occur
(influenced by cytokines)
• Myeloblasts, promyelocytes,
myelocytes, metamyelocytes,
band cells
mature neutrophils or
eosinophils or basophils.
Hemopoiesis
Myeloblast.
Promyelocyte.
Myelocyte.
Metamylocyte.
Band Form
Kinetics of Granulopoiesis
• Takes 2 weeks in the bone marrow
- 1 week for mitotic /proliferative phase
- 1 week for post mitotic /differentiation phase
(from metamyelocyte to mature granulocyte)
- ½ of the PMNs leave the peripheral blood in 6-8 hours
- 1-2 days in CT, then destroyed by apoptosis and
engulfed by macrophages
- Large numbers of PMNs also lost into the lumen of the GI
tract and feces
Kinetics of Granulopoiesis 46
• Large reserve pool of PMNs present in bone marrow
• Reserve pool in blood vessels also
- freely circulating pool
- marginated pool in small blood vessels can be
recruited quickly; in dynamic equilibrium with the
circulating pool
Hemopoiesis
Kinetics of Granulopoiesis 47
• Fate of hemopoietic cells and stages of hemopoiesis
regulated by
- transcription factors
- signalling molecules
- erythropoietin and thrombopoietin
- colony-stimulatng factors (CSFs)
- cytokines
- interleukiins
Hemopoiesis
Development of Monocytes
48
• CMP stem cell GMP stem cell monocyte-progenitor (MoP)
cell
• MoP cell (bone marrow) to monocyte (blood) takes approx 55
hours
• Monocyte remains in circulation for 16 hours before emigrating
and differentiating to a tissue macrophage.
(interleukins, CSFs and transcription factors control this
proliferation and differentiation process)
Hemopoiesis
Attn :
• HSC: hematopoietic stem cell,
• CLP: common lymphoid progenitor,
• CMP: common myeloid progenitor,
• MEP: Megakaryocyte/erythrocyte progenitor, GMP:
granulocyte/macrophage progenitor, MkP: Megakaryocyte
progenitor,
• EP: erythrocyte progenitor,
• GP: granulocyte progenitor,
• MacP: macrophage progenitor,
• DC: dendritic cell,
• NK: natural killer, Lin: lineage markers.
Development of Lymphocytes (Lymphopoiesis)
• HSC CLP : dependent on transcription factors
• Main site for lymphopoiesis is the bone marrow
• continuous proliferation occurs in the peripheral lymphatic
organs
• CLP cells express the GATA -3 transcription factor
• pre T lymphocytes form, which leave the bone marrow and
enter the THYMUS.
• Long-lived small T lymphocytes then enter the circulation
Hemopoiesis
Development of Lymphocytes 52
(Lymphopoiesis)
• CLP cells also express the Pax5 transcription factor,
which activates specific CLP cells bone marrow, gut-
associated lymphatic tissue and the spleen
• B lymphocytes further develop in these bursa-
equivalent organs
Hemopoiesis
Development of Lymphocytes
(Lymphopoiesis) 53
• CLP Pre-NK cell in bone marrow
• NK cells probably develop under the influence
of IL-2 and IL-15
• Development may also occur in the fetal
thymus and lymph node
Hemopoiesis
