Hematopoietic system:

Peripheral blood and Bone marrow

Ibrahim A.
Department of Anatomy
Faculty of Basic Medical Sciences
University of Ilorin

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 Lecture expectations
n At the end of the lecture, students should be able to:
1. Describe the composition of normal peripheral blood, including the
relative quantities of the blood cells.
2. Identify normal peripheral blood cells.
3. Describe the function and "life cycle" of normal peripheral blood cells.
4. List the components of the CBC (complete blood count).
5. List the types of hematopoietic tissues.
6. Describe the development of hematopoiesis throughout the life of the
individual.
7. Describe the developmental stages of erythroid and myeloid cells.
8. Identify the other types of cells in the bone marrow,
9. Describe the factors which control hematopoiesis, e.g. growth factors
such as erythropoietin, GMCSF. 2-2
 1. Peripheral blood
n Blood is a fluid connective tissue constituting about 7% of
our total body weight (about 5 liters in the human).
n The primary components of blood are:
A. Plasma: The liquid in which peripheral blood cells are suspended.
n Composed of water, electrolytes such as Na+ and Cl, (0.9%), 7%
plasma proteins (such as albumin, fibrinogen, globulins), hormones,
fats, amino acids, vitamins carbohydrates, lipoproteins as well as other
substances.
n The normal plasma volume is 40 ml/kg of body weight.
B. Formed Elements (blood cells):
1. Erythrocytes (red blood cells or rbc): occupy about 40-45% of the
total blood volume or 30ml/kg body weight.
2. Leukocytes (white blood cells or wbc) and Platelets: together
make up about 1-2% of the total blood volume.
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2-4
Blood smear: Wright or Giemsa stain methods

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 Blood Cells
Morphology and function

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 A. Erythrocytes (Mature red blood cells)

n Normal number:
n (4.2-5.5)X1012/L in male
n (3.5-5.0)X1012/L in female
n Structure:
n biconcave discs in shape
n 7.5-8.5 µm in diameter and 1-2 µm
thick
n no nucleus and organelles
n filled with hemoglobin, Hb (about
1/3)
n normal number:

n 120-150g/L in male
n 105-135g/L in female 2-7
 Erythrocytes (Mature red blood cells)
n Erythrocyte membrane skeleton:
n change shape
n main component is spectrin and actin
n Blood type antigen: A, B:
n membrane protein
n ABO blood type
n hemolysis→erythrocyte ghost
n Life span:
n approximately 120 days in the
circulation.
n As red blood cells age, the surface
area decreases relative to cytoplasmic
volume. 2-8
 Erythrocytes (Mature red blood cells)
n Hematocrit: a measure of the total volume of the erythrocytes relative
to the total volume of whole blood in a sample.
n The result is a proportion, often expressed as a percent.
n Normal range is 37-47% for women, and 42-52% for men.
n Anemia: is defined as a significant reduction in the total body
erythrocyte mass, measured as a reduction in the RBC count, the
hemoglobin, and the hematocrit.
n Anemia exists when the hemoglobin is less than 120 g/L or the hematocrit
is less than 37%.
n Classification
n cytometric schemes (microcytic, macrocytic, or normocytic),
n erythrokinetic schemes (those that take into account the rates of RBC
production and destruction), and
n biochemical/molecular schemes (those that consider the etiology of the
anemia at the molecular level).
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 Reticulocyte (immature erythrocyte)
n Reticulocytes are red blood cells
released from the bone marrow into
the peripheral circulation are
considered reticulocytes for about 2
days.
n Slightly larger than the older RBCs and
have slightly more RNA, giving them a
slightly bluish staining quality (referred
to as polychromasia).
n Can be identified by staining with a
supravital dye that stains the RNA.
n 0.5-1% of total erythrocyte population
or 3-6% in neonate
n will disappear after 1-3 days
n life span: 120 days
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B. Leucocytes: (White blood cells)
n A group of large cells with nucleus.
n Involve in defense and immune reaction.
n Normal number: (4.0-10) X109/L
n Classification:
n Granulocytes (Polymorphonulcear leucocytes):
n neutrophil
n Eosinophil
n Basophil
n Agranulocytes (mononuclear leucocytes):
n monocyte
n lympocyte

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 Granulocytes: neutrophil
n Normal percentage: 50-70% of total
leukocyte population
n Function: phagocytose bacterium;
n specific granule kill bacteria
n azurophilic granule digest bacteria
n Life span:
n In blood 6-8 hours,
n In connective tissue 2-3 days
n Structure (LM):
n round, 10-12 µm in diameter
n rob-liked or poly morphous nucleus, 2-
5 lobes
n fine neutrophilic granules-pink
cytoplasm 2-12
 Granulocytes: neutrophil
n Structure (EM)
n Granules: Cytoplasm contains two major
types of granules:
n Specific granules (80%)
n small, 0.3-0.4 µm
n ovoid or irregular in shape
n contain: collagenase, lactoferrin,
bacteriocidal, lysozyme, phagocytin
(defensin),
n Stain pinkish
n azurophilic granule (20%)
n large, round or ovoid , 0.6-0.7µm
n electron dense
n lysosome: acid phosphatase,
peroxidase, acidic hydrolase
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n Stain reddish purple
 Granulocytes: eosinophil
n Normal percentage: 0.5-3% of total
leukocyte population
n function:
n counteract the infection of parasite
n reduce allergic reaction
n Life span:
n in blood 6-8 hour,
n in connective tissue 8-12 days
n Structure (LM):
n round,10-15µm in diameter
n 2 lobes nucleus
n rough bright red granules-acidophilic
granules
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 Granulocytes: eosinophil
n Structure (EM):
n Granules:

n round or ovoid
n with cube-liked electron
dense crystal
n contain:
n ACPase
n Histaminase
n peroxidase

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 Granulocytes: basophil
n Normal percentage: 0-1% of total
leukocyte population
n Function: involve in allergic reaction
n Life span: 10-15 days
n Structure (LM):
n less, round 10-12 µm
n lobe, “S” shaped or irregular nucleus
n Basophilic granule: contains heparin,
histamine and acidophil chemotactic
factor
n cytoplasm: contain leukotriene

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 Agranulocytes: monocyte
n Normal percentage: 3-8% of total leukocyte
population
n function: actively mobile and chemotaxis
n Life span: in blood 1-5 days, in CT which become
into macrophage- mononuclear phagocytic system,
MPS
n Structure (LM):
n large round, 14-20 µm
n nucleus appear as kidney, horse-shoe or ovoid in
shape
n cytoplasm: gray-blue in color, contain fine azurophilic
granules.
n Structure (EM):
n azurophilic granule: lysosome- contain peroxidase,
ACPase,non-spacial esterase and lysozyme
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n cell membrane has many finger-like microvilli.
 Agranulocytes: lymphocyte
n normal percentage: 20-30% of total
leukocyte population
n function: involve in immune response
n Structure (LM):
n round, small lymphocyte 6-8 µm,
medium-sized lymphocyte 9-12 µm,
large lymphocyte 13-20 µm in
diameter
n round nucleus with indentation,
chromatin appears as spot-liked and
electron-dense
n cytoplasm: bright blue in color, less
azurophilic granule

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 Agranulocytes: lymphocyte
n Structure (EM): free ribosome, mitochondrial, RER
n Classification: T-lymphocytes, B-lymphocyte, Large
granular cell (killer cells and natural killer cells)
n T-lymphocytes: thymus dependent lymphocyte, 75%,
involve in cellular immune reaction and regulate immune
response.
n Participate in cell-mediated immunity (such as graft
rejection)
n Some T-cells (cytotoxic) can elaborate cytotoxic agents.
n They can make lymphokines (including interferon,
macrophage migration inhibitor factor, chemotactic factors
for basophils).
n There are also memory T-cells that survive for years or
decades.

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 Agranulocytes: lymphocyte
n B-lymphocyte: bone marrow dependent lymphocytes, 10-15%,
n become into plasma cell in tissue: Plasma cells produce antibodies
(immunoglobulins).
n involve in humoral immune response
n these cells play a central role in humoral or antibody-mediated immunity.
n Some divide and differentiate into plasma cells in tissue. Some are memory
cells.
n They are immunologically characterized by immunoglobulin on their cell
membrane.
n Large granular cell: KC (killer cell) and NKC (nature killer cell), 10%.
n NK cells lack the surface antigens of T and B cells and do not require prior
stimulation to attack virus-infected cells or tumor cells

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 C. Blood Platelet
n Derived from bone marrow
megakaryocytes.
n normal number: 100-300X109/L
n Life span is 7-10 days.
n The platelet count is typically reported
with the CBC or FBC
n Structure (LM):
n Non-nucleated flat,
n biconvex,
n round or ovoid disks (2-5 µm diameter)
n irregular in shape
n Contain hyalomere and granulomere

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 C. Blood Platelet
n Structure (EM):
n cell coat:
n glycosaminoglycan and glycoprotein
n tubular systems:
n opening tubule system- increasing the exchange area, facilitate
the intaking and releasing
n dense tubule system- SER, collecting Ca2+ and synthesizing
prostaglandin
n granules:
n specific granule:
n mediate electron density, with dense core, contains clotting factor,
fibrinogen, acidic hydrolase
n dense granule:
n electron dense, contains serotonin(5-hydroxytryptamine),
ADP,ATP, Ca2+ and adrenalin 2-22
C. Blood Platelet
n Function:
n involve in clotting and stopping
the bleed:
n Aggregation
n release components of granule,
make thrombinogen become
into thrombin, then later make
fibrinogen become into fibrin
n protecting endothelium and take
part in repairing of endothelium

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 2. Bone marrow and hemetopoiesis
n Bone marrow is a richly vascularized connective tissue which
specializes in production of all the formed elements of blood. Bone
marrow is the most rapidly replicative tissue in the body.
n The different blood cells have finite and often brief life spans and
must be renewed to maintain appropriate circulating levels.
n The process of renewal is known as hematopoiesis (hemopoiesis).
n Influences on hematopoiesis
n Infection, hemorrhage, tumors and other factors may induce increases or
decreases in the level of hematopoiesis in one or more of the blood cell
lines
n Several growth factors and other products affect the proliferation and
differentiation of hematopoietic cells. Different factors are involved in
erythropoiesis, granulopoeisis, etc.
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 Hematopoietic tissues
n Tissues which actively or potentially produce blood
cells are hematopoietic tissues.
n Types of hematopoietic tissues
A. Myeloid tissues
n Blood forming tissues identified as the "red marrow" of bones.
The amount and location of red marrow is different in the fetus
and the adult.
B. Lymphoid tissues
n Some lymphocytes of peripheral blood arise from proliferation
within lymphoid tissues.
n Lymphoid tissues are elements of the larger lymphatic system
(lymph nodes, tonsils, Peyer's patches, etc.)

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 Places for Hematopoiesis: Embryo
n Embryo and fetus (intrauterine development)
a) Mesoblastic phase
n Mesoblastic phase extends from two weeks to two months. Hematopoiesis
begins in the yolk sac wall where small nests of blood cell production can
be visualized. These nests are referred to as "blood islands".
b) Hepatic phase
n Islands of blood cell development occur within the liver parenchyma from 6
weeks to birth.
n Although the liver is the dominant site of hematopoiesis for the first half of
gestation, blood cell production also occurs at lesser intensity within the
spleen.
c) Myeloid phase
n Hematopoiesis within bone marrow begins in the clavicle at about 2 1/2
months. Myeloid hematopoiesis is centered in most bone marrow (red
marrow) during intrauterine life. 2-26
Places for Hematopoiesis: Birth & Adults
n Birth
n At birth, the myeloid phase predominates in hematopoiesis
and occurs in the medullary cavities of long bones.
n As a child grows, the long bones assume the weight bearing
function and the marrow becomes yellow. The site of
hematopoiesis subsequently shifts to the red marrow of the
axial skeleton.
n Adults
n Under normal conditions, hematopoiesis resides in red
marrow of the axial skeleton. However, under certain
conditions, the spleen, liver and yellow marrow (converts to
red) can resume hematopoietic activity in the adult.

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 Structure of bone marrow
n Histology:
n Red marrow is composed of a
network of vascular sinuses
(specialized blood vessels) situated
throughout a sponge-like network of
hematopoietic cells.
n Sinuses are interposed between
arteries and veins and contain,
essentially, peripheral blood.
n Red marrow is organized into sacs
(alveoli) within which hematopoietic
cells develop in nests or foci.
n Reticular cells and reticular fibers
form a supportive framework for the
developing blood cells and sinuses
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 Structure of bone marrow
n Location
n In red marrow, cells of the RBC
line develop near the sinus wall.
n Each RBC nest has an
associated macrophage which
contains iron.
n Cells of the granulocyte series
(eosinophilic, neutrophilic, and
basophilic) develop away from
the sinus.
n Megakaryocytes (cells
producing platelets) also
develop next to sinuses

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 Developmental stages of Blood Cells
n Erythropoiesis (RBCs): Process of formation and differentiation of RBCs.
1. Proerythroblast - divides.
2. Basophilic erythroblast – divides
3. Polychromatophilic erythroblast - divides.
4. Orthochromic erythroblast - no division.
5. Reticulocyte - no division.
6. Erythrocyte - no division.
7. Control of erythropoiesis
n Development from a basophilic normoblast to a mature erythrocyte involves 16-32
cell divisions and takes approximately one week.
n RBC formation is under the control of a kidney produced hormone known as
erythropoietin.
n Dietary iron, Vitamin B12 and folic acid are required for the normal production of
RBCs. 2-30
Stages of Erythropoiesis (RBCs)

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 Developmental stages of Blood Cells
n Granulopoiesis: Process of formation and differentiation of
granulocytes.
1. Myeloblast - divides.
2. Promyelocyte - divides.
3. Neutrophilic, eosinophilic, or basophilic myelocyte - divides.
4. Neutrophilic, eosinophilic, or basophilic metamyelocyte - no
division.
5. Neutrophilic, eosinophilic, or basophilic band - no division.
6. Segmented neutrophil, eosinophil, or basophil - no division.

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Stages of granulopoiesis

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 Developmental stages of Blood Cells
n Thrombopoiesis: Process of formation of platelets.
1. Megakaryoblast - Large cell with a big nucleus (4n) situated close to
sinuses.
2. Promegakaryocyte – Larger than a megakaryoblast, this cell contains a
voluminous polyploid nucleus (8n). Develops platelet demarcation
channels.
3. Megakaryocyte - A giant cell with a large polyploid nucleus (32n-64n).
Platelet demarcation channels very distinct. A massive protrusion of the
cell penetrates a sinus and fragments into platelets.
4. Thrombocyte (platelet) -The final end product which circulates in the
peripheral blood. Responsible for primary hemostasis (clot formation).
5. Control of thrombopoiesis - A serum glycoprotein, known as
thrombopoietin, has been demonstrated. Thrombocytopenia stimulates
megakaryocytes and platelet production.
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Stages of Thrombopoiesis

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Pluripotent Stem cell

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Pluripotent Stem cell

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 Other red marrow cells
1. Macrophages
n These cells are the tissue counterparts of monocytes of the
peripheral blood.
n In the bone marrow, they function in phagocytosis and iron storage.
(Sometimes we refer to macrophages as histiocytes).
2. Structural cells
n These include fat cells (adipocytes), reticular cells, and endothelial
cells.
3. Lymphocytes
n A few lymphocytes and plasma cells are usually present in the bone
marrow.
4. Mast cells
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QUESTIONS?

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