BLOCK IV: MODULE I: HEMETOPOIETIC

SYSTEM

HOW COMPLETE IS A CBC?

HEMATOPOIESIS formation, development and
specialization of all functional blood cells.

COMPONENTS OF BLOOD:

BLOOD

1.

a connective tissue composed of a liquid

extracellular matrix called blood plasma that
dissolves and suspends various cells and cell
fragments.
It contributes to homeostasis by transporting O2,
CO2, nutrients and hormones to and from the
bodys cells. Blood transports O2 from the lungs
and nutrients from the GIT. The O2 and nutrients
diffuse from the blood into the interstitial fluid and
then into body cells. CO2 and other wastes move
from body cells to interstitial fluid to blood. Blood
then transports the wastes to various organs the
lungs, kidneys and skin for elimination from the
body.
It helps regulate body pH and temperature, and
provides protection against disease through
phagocytosis and the production of antibodies.

2.

TRANSPORTATION. Blood transports O2 from the

lungs to the cells of the body and CO2 from the
body cells to the lungs for exhalation. It carries
nutrients from the GIT to body cells and hormones
from endocrine glands to other body cells. Blood
also transports heat and waste products to various
organs for elimination from the body.
REGULATION. Circulating blood helps maintain
homeostasis of all body fluids. Blood helps regulate
pH through the use of buffers. It also helps adjust
body temperature through heat absorbing and
coolant properties of water in blood plasma and its
variable rate of flow through the skin, where excess
heat can be lost from the blood to the
environment. Blood osmotic pressure influences
the water content of cells, mainly through
interactions of dissolved ions and proteins.
PROTECTION. Blood can clot, which protects
against its excessive loss from the cardiovascular
system after an injury. Its white blood cells protect
against disease by carrying on phagocytosis. Blood
proteins, such as antibodies, interferons, and
complement, also help protect against disease.

About 91.5% water and 8.5% solutes (mostly

proteins)
Plasma proteins proteins confined to the blood.
These proteins maintain proper blood osmotic
pressure, which is an important factor in the
exchange of fluids across capillary walls.
Hepatocytes (liver cells) synthesize most of the
plasma proteins, which include albumin (54%),
globulin (38%), and fibrinogen (7%).
Antibodies or Immunoglobulins foreign
substances (antigens) such as bacteria and viruses
stimulate the production of these during immune
responses and enables the invading antigen.
Other solutes in plasma include electrolytes,
nutrients, regulatory substances such as enzymes,
hormones, gases and waste products such as urea,
uric acid, creatinine, ammonia and bilirubin.

CONSTITUENTS
Water (91.5%)

Plasma Proteins
(7.0%)

Albumins

PHYSICAL PROPERTIES:

Blood Plasma watery liquid extracellular matrix

that contains dissolved substances
Formed elements cells and cell fragments
If blood is centrifuged, cells sink to the bottom of
the tube while the lighter-weight plasma forms a
layer on top.

BLOOD PLASMA

FUNCTIONS OF BLOOD:

Blood volume is 5-6 liters (1.5 gal) in an averagesized adult male and 4-5 liters (1.2 gal) in an
average-sized adult female.
Several hormones, regulated by negative feedback,
ensure blood volume and osmotic pressure remain
relatively constant. Especially aldosterone, ADH
and atrial natriuretic peptide, which regulate how
much water is excreted in the urine.

Globulins
and Globulins

Denser and more viscous than water and feels

slightly sticky
Temperature 38oC (100.4oF), 1oC higher that oral
or rectal body temp.
pH slightly alkaline from 7.35 7.45
constitutes about 20% of extracellular fluid,
amounting to 8% of total body mass.

Globulin

DESCRIPTION
Liquid portion of blood. Acts
as solvent & suspending
medium for components of
blood; absorbs, transports &
releases heat.
Exert colloid osmotic
pressure, w/c helps maintain
water balance between
blood& tissues and
regulates blood volume.
Smallest & most numerous
blood plasma proteins;
produced by liver. Function
as transport proteins for
several steroids hormones
and for fatty acids.
Produced by liver. Alpha &
beta globulins transport
iron, lipids, and fat-soluble
vitamins.
Antibodies of immune
defense. Antibodies help
attack viruses and bacteria.
Produced by plasma cells,
which develop from B
lymphocytes.

Clotting Proteins
Fibrinogen,
Prothrombin,
Accelerator
Globulin
Complement
Proteins
C1 to C9
Plasma lipoproteins
Chylomicrons
Very low-density
lipoproteins (VLDL)
Low-density
lipoproteins (LDL)
Other Solutes
(1.5%)
Electrolytes

Nutrients

Gases

Regulatory
Substances

Waste Products

Produced by liver. Plays

essential role in blood
clotting by formation of
fibrin threads.

Produced by liver. Its

function is for destruction of
microorganisms and
initiation of inflammation.
Produced by the intestinal
epithelial cells and
transports triglycerides to
the liver.
Produced by the liver and
transports triglycerides from
liver to body cells.
Produced by the liver and
transports cholesterol from
liver to body cells.

Inorganic salts. Positively

charged ions (cations)
include Na+, K+, Ca2+, Mg2+;
negatively charges ions
(anions) include Cl-, HPO42-,
SO42-, and HCO3-. Help
maintain osmotic pressure
and play essential roles in
the function of cells.
Products of digestion pass
into blood for distribution to
all body cells. Include amino
acids (from proteins),
glucose (from carbs), fatty
acids and glycerol (from
triglycerides), vitamins and
minerals.
O2, CO2, and N2. More O2 is
associated with hemoglobin
inside RBCs; more CO2 is
dissolved in plasma. N2 is
present but no known
function in body.
Enzymes, produced by body
cells, catalyze chemical
reactions. Hormones,
produced by endocrine
glands, regulate
metabolism, growth and
development. Vitamins are
cofactors for enzymatic
reactions.
Most are breakdown
products of protein
metabolism and are carried
by blood to organs of
excretion. Include urea, uric
acid, creatine, Creatinine,
bilirubin and ammonia.

HEMATOPOIETIC DEVELOPMENT
3 phases:
MESOBLASTIC PERIOD

Only erythroblasts develop from yolk sac and that

hematopoietic stem cells arise from an
intraembryonic source near the aorta.
Hematopoietic stem cells seed the fetal liver at 5
weeks of gestation.
The early hematopoiesis is transient, ceasing at 6-8
weeks of gestation.
Measurable hematopoietic products at this time
include Portland, Gower 1, and Gower 2
Hemoglobins.

HEPATIC PERIOD

FORMED ELEMENTS

Red Blood cells, White Blood cells and platelets.

RBCs & WBCs are whole cells; platelets are cell
fragments.
HEMATOCRIT percentage of total blood volume
occupied by RBCs. (N.V. females: 38 46%;
males: 40 54% )
Testosterone, present in much higher concentration
in males, stimulates synthesis of erythropoietin,
the hormone that in turn stimulates the production
of RBCs.
Lower values in women during reproductive years
also may be due to excessive loss of blood during
mens.
Significant drop in hematocrit indicates anemia
while abnormally high percentage of RBCs
indicates polycythemia. This raises the viscosity of
blood, which increases resistance to flow and
makes the blood more difficult for the heart to
pump.
Increased viscosity of blood leads to high blood
pressure and increased risk of stroke.
Causes of polycythemia increased RBC
production, tissue hypoxia, dehydration, and blood
doping or use of EPO by athletes.

3 Principal components:

At gestational weeks 4-5, clusters of erythroblasts,

granulocytes, and monocytes appear in the fetal
liver.
The liver remains the major site of hematopoiesis
during getal life, retaining activity until 1-2 weeks
after birth.
By the third month of embryonic development, the
liver reaches its peak in both erythropoiesis and
granulopoiesis.
During this stage of intrauterine life, RBCs are
present in all forms of maturity erythropoiesis.
Erythrocytes arise from endothelial cells lining the
sinusoids and from the erythroblasts associated
with them. By the end of third month, these
primitive cells have disappeared entirely.
Megakaryocytic development together with splenic
activity involving erythropoiesis, granulopoiesis,
and lymphopoiesis is observed.
Hematopoietic activity has begun in the lymph
nodes and the thymus.

Splenic activity gradually decreases, terminating

granulopoiesis.
The thymus is the first organ of the lymphatic
system to develop fully in the fetus. It continues to
grow and enlarge involving itself solely with
lymphocyte specialization.
Measurable products in the hepatic period include
primitive erythroblasts, definitive erythroblasts,
granulocytes, monocytes, lymphocytes,
megakaryocytes, and Hemglobins F, A, and A2.

RED MARROW

MEDULLARY (MYELOID) PHASE

5TH Month of fetal development, mesenchymal cells

begin to differentiate into blood cells of all types.
Medullary production begins with ossification and
development of marrow within the core of the
bone.
The clavicle is the first bone to demonstrate
marrow hematopoietic activity. This is followed by
rapid ossification of the entire skeleton with
subsequent development of active marrow.
Bone marrow activity increases resulting in
extremely hyperplastic red marrow.
By the 6th month, the marrow has become the
primary site of hematopoiesis.
Measurable products include all mature cells,
erythropoietin (EPO), fetal and adult hemoglobins.

ADULT HEMATOPOIETIC TISSUE

BONE MARROW

In times of excessive loss of blood or destruction of

red marrow by chemicals or irradiation, the
mesenchymal cells, having retained their potential
to transform and revert to red marrow, engage in
hematopoiesis.
Since this hematopoiesis occurs outside the bone
marrow, it is referred to as extramedullary
hematopoiesis.

Early in bone formation, a space is left at the

center by the resorption first of cartilage and then
of endosteal bone.
This space is invaded by the mesenchyme, which
develops into an organ entity.
The mesenchyme develops into 3 types of cells
that gives rise to reticular tissue, adipose tissue,
and hematopoietic tissue.
Some of the reticular cells in the bone marrow are
positioned on the outside surface of the venous
sinuses, their long narrow branches extending into
the perivascular space, thus providing support for
the developing hematopoietic cells, macrophages
and mast cells.
During childhood, the marrow remains exclusively
red. By ages 5-7 years, fat appears in the long
bones in the areas previously occupied by red
marrow.
Retrogression occurs, and thus active red marrow
is restricted to the flat bones, sternum, vertebra,
pelvis, ribs, skull, and proximal portions of the long
bones.
Hematopoietic cells gradually disappear from
specific areas, leaving only reticular tissue and fat
cells, which constitute yellow marrow.
Yellow marrow proper is an admixture of fat cells
and undifferentiated mesenchymal cells and
macrophages, scattered throughout the red
marrow.
The yellow marrow serves as a storage organ (fat)
and as a reserve of hematopoietic tissue.

The arrangement of the red marrow consists of

extravascular cords composed of all developing
blood cell lines, stem cells, adventitial cells, and
macrophages. This area is separated from the
lumen of the sinusoids by endothelium and
adventitial cells.
The erythrocytes are localized to small clusters
against the outer surfaces of the vascular sinuses,
some are characteristically found surrounding ironladen macrophages.
The megakaryocytes are directly outside the
vascular walls of the sinusoids; this location
facilitates release of their platelets into the lumen
of the sinusoids.
The granulocytic cells are situated deeper in the
cords until the maturation of the metamyelocyte,
at which time they move closer to the vascular
sinuses.
All cells leaving the marrow penetrate the
sinusoidal wall by passing between adventitial cells
and egressing through spaces in the endothelial
lining.

FORMATION OF BLOOD CELLS

Negative feedback systems regulate the total

number of RBCs and platelets in circulation, and
their numbers remain steady.
The abundance of the different types of WBCs
however, varies in response to the challenges by
invading pathogens and other foreign antigens.
The process by which the formed elements of the
blood develop is called HEMOPOIESIS or
HEMATOPOIESIS.
Before birth, Hematopoiesis first occurs in the yolk
sac of an embryo and later in the liver, spleen,
thymus and lymph nodes of a fetus.
Red Bone Marrow becomes the primary site of
hematopoiesis in the last three months before
birth, and continues as the main source of blood
cells after birth and throughout life.
Red Bone Marrow is a highly vascularized
connective tissue located between the trabeculae
of spongy bone tissue. It is present chiefly in bones
of the axial skeleton, pectoral and pelvic girdles,
and the proximal epiphyses of the humerus and
femur.
About 0.05 0.1% of red bone marrow cells are
derived from mesenchymal cells called
PLURIPOTENT STEM CELLS or HEMOCYTOBLASTS.
These cells have the capacity to develop into
several different types of cells.

In Newborns, all bone marrow is red and thus

active in blood cell production.
As an individual grows into adulthood, the rate of
blood cell formation decreases; the red bone
marrow in the medullary cavity of long bones
becomes inactive and is replaced by the yellow
bone marrow, which is largely fat cells.
Under certain conditions such as severe bleeding,
yellow bone marrow can revert to bone marrow by
extension of red bone marrow into yellow bone
marrow and repopulation of yellow bone marrow by
pluripotent stem cells.
Stem cells in the red bone marrow reproduce
themselves, proliferate and differentiate into cells
that give rise to blood cells, macrophages, reticular
cells, mast cells and adipocytes.
Some of the stem cells can also form osteoblasts,
chondroblasts, and muscle cells and someday may
be used as a source of bone, cartilage, and
muscular tissue for tissue and organ replacement.
The reticular cells produce reticular fibers, which
form the stroma that supports red bone marrow
cells.
Once blood cells are produced in red bone marrow,
they enter the blood stream through sinusoids,
enlarged and leaky capillaries that surround the red
bone marrow cells and fibers. With the exception of
the lymphocytes, formed elements do not divide
once they leave red bone marrow.
In order to form blood cells, pluripotent stem cells
in red bone marrow produce two further types of
stem cells, called MYELOID STEM CELLS and
LYMPHOID STEM CELLS.
MYELOID STEM CELLS begin their development in
red bone marrow and give rise to RBCs, platelets,
monocytes, neutrophils, eosinophils, and basophils.
LYMPHOID STEM CELLS begin their development in
the red bone marrow but complete it in lymphatic
tissues; they give rise to lymphocytes.
During hematopoiesis, some of the myeloid stem
cells differentiate into PROGENITOR CELLS. Other
myeloid stem cells and the lymphoid stem cells
develop directly into precursor cells.
PROGENITOR CELLS are no longer capable of
reproducing themselves and are committed to
giving rise to more specific elements of blood.
Some progenitor cells are known as COLONYFORMING UNITS (CFUs).
CFU-E produces erythrocytes (RBCs)
CFU-Meg produces megakaryocytes, source of
platelets
CFU-GM produces granulocytes and monocytes.
In the next generation, the cells are called
PRECURSOR CELLS, also known as BLASTS. Over
several divisions, they develop into the actual
formed elements of blood. Ex: Monoblasts develop
into monocytes, eosinophilic myeloblasts develop
into eosinophils, etc. Precursor cells have
recognizable microscopic appearances.
Several hormones called HEMOPOIETIC GROWTH
FACTORS regulate the differentiation and
proliferation of particular progenitor cells.
ERYTHROPOIETIN or EPO increases the number of
RBC precursors. EPO is produced primarily by cells

in the kidneys that lie between the kidney tubules

(peritubular interstitial cells). With renal failure,
EPO release slows and RBC production is
inadequate.
THROMBOPOIETIN or TPO is a hormone produced
by the liver that stimulates the formation of
platelets (thrombocytes) from megakaryocytes.
Several different cytokines regulate development
of different blood cell types. CYTOKINES are small
glycoproteins that are typically produced by cells
such as red bone marrow cells, leukocytes,
macrophages, fibroblasts, and endothelial cells.
They act as local hormones. They stimulate
proliferation of progenitor cells in red bone marrow
and regulate the activities of cells involved in nonspecific defenses (such as phagocytes) and
immune responses (such as B cells and T cells).
Two important families of cytokines that stimulate
white blood cell formation are COLONY
STIMULATING FACTORS (CSFs) and INTERLEUKINS.

ERYTHROCYTE PRODUCTION
GROWTH FACTOR: erythropoietin
NORMOBLASTIC MATURATION
A. PRONORMOBLAST or RUBRIBLAST earliest
recognizable erythroid precursor
Size: 14-19 micrometers in diameter; largest of
the erythroid precursor
Nucleus: has fine, uniform chromatin pattern,
and more distinct & intensely stained than that of
the myeloblast. It usually occupies more than 80%
of the cell and is round to slightly oval.
Nuclear Membrane: prominent
Nucleoli: 3-5
Cytoplasm: heterogenous in quality, & intensely
basophilic; no granules present; has highest RNA
content
The pronormoblast undergoes mitosis and forms
two basophilic normoblasts.
B. BASOPHILIC NORMOBLAST or
PRORUBRICYTE
Size: somewhat smaller than rubriblast; 12-17
micrometers in diameter
N/C ratio: moderate; about of the total cell
area is cytoplasm
Nucleus: round
Nuclear Chromatin: slightly coarser chromatin
which stains intensely; chromatin maybe partially
clumped & the pattern may suggests a wheel with
broad spokes. Parachromatin (non-chromatin
part of the nucleus) is distinct and stains pink.
Nucleoli: present but not often visible
Cytoplasm: deeply basophilic owing to
abundance of RNA. The cell borders of early
normoblasts are made irregular; has a highest
RNA content.
The basophilic normoblast undergoes mitosis &
gives rise to polychromatophilic normoblast.
C. POLYCHROMATOPHILIC NORMOBLAST or
RUBRICYTE

There is continuing Hemoglobin production &

becomes visible in the cytoplasm of the 2
daughter cells as polychromasia (mixture of redstaining of hemoglobin with the blue of the RNA in
varying shades of gray).
Size: slightly smaller than basophilic normoblast;
12-15 micrometers in diameter
Nucleus: occupies about half of the area of the
cell; round & may be eccentric
Nuclear Chromatin: stains intensely & has
moderately condensed chromatin & which is
sharply distinct from the pink parachromatin.
Cytoplasm: shows polychromasia; RNA
production starts to decline.
The polychromatophilic normoblast undergoes
one or two mitotic divisions.

D. ORTHOCHROMATIC NORMOBLAST or
METARUBRICYTE
After mitosis the nucleus becomes small & dense
and after this mitosis is no longer possible.
This is the last nucleated erythrocyte stage.
Size: cell is smaller than polychromatophilic
normoblast; 8-12 micrometers in diameter
N/C ratio: lower than polychromatophilic
normoblast
Nucleus: pyknotic
Cytoplasm: contains more abundant hemoglobin
& fewer polyribosomes and paler & remains
slightly polychromatophilic (blue-gray-violet to
pinkish).
Finally, accompanied by cytoplasmic
contractions & undulations, the nucleus & a
small rim of cytoplasm are ejected from the
orthochromatic normoblast forming the
reticulocyte. This is after 3-4 mitosis (3 days)
and forms 16 reticulocytes.

Normally, reticulocytes remain as such, slowly

synthesizing hemoglobin, for one day in the marrow
and one day in the blood. The mature erythrocytes
circulate for about 120 days. During this time, they
gradually age, certain enzymatic activities diminish
and are finally destroyed within phagocytic cells of the
RES.

E. RETICULOCYTE or DIFFUSELY BASOPHILIC

ERYTHROCYTE
Anucleated cell, which stains on air-dried films
with Romanowsky stains
Size: larger than mature red cells and are sticky;
7-8 micrometers in diameter. Remain in the
marrow for 1-2 days before released into the
blood.
Cytoplasm: stains polychromatophilic due to
retention of RNA. RNA synthesis stops, yet the
residual RNA that is left remains for a few days
and protein & heme synthesis continues in the
reticulocyte until the cell loses its RNA &
mitochondria. May have irregular cytoplasmic
borders.

MEGALOBLASTIC MATURATION

In the marrow, reticulocytes are slightly greater in

number than the reticulocytes in the circulating blood.
If sufficiently severe hypoxia is present, the marrow
pool of reticulocytes can be released. This
approximately doubles the number of circulating
reticulocytes.
F.

The most numerous cells of blood, and are

responsible for the transport of O2 and CO2 to and
from the tissues of the body.
Resembles biconcave-shaped disk 7.5
micrometers in diameter, 2.0 micrometers
thick at its center. This shape provides the
cell with a large surface area relative to its
volume, thus enhancing its capability for
gaseous exchange. It has a life span of 120
days.
RBCs plasma membrane is strong and
flexible which allows them to deform without
rupturing as they squeeze through narrow
capillaries.
The cytosol of RBCs contain hemoglobin
molecules.
Although erythrocyte precursor cells within
the bone marrow possess nuclei, during
development and maturation the precursor
cells of erythrocytes expel not only their
nuclei but also all of their organelles before
entering the circulation. Thus, mature
erythrocytes have no nuclei.
RBCs have a salmon-pink color when stained with
Wrights stain.
Males have more RBCs than females. Males 5M;
females 4.5M per mm3). People living at higher
altitudes have more RBCs than residents living at
lower altitudes.

Abnormal maturation of erythroid precursors that

occurs in Vit. B12 deficiency or folic acid
deficiency is known as megaloblastic, and the
abnormal erythroid cells are called megaloblasts.
Mechanism: coz of impaired ability of the cells to
synthesize DNA, the intermitotic phase as well as
the mitotic phase is prolonged. This results in
enlarged cells, with nuclear maturation lagging
behind cytoplasmic maturation (cytonuclear
dissociation).
Morphology: nuclear chromatin pattern is more
delicate & more open with prominent
parachromatin. Kayorrhexis and Howell-Jolly
bodies are frequently noted.
Megaloblastic development parallels normoblastic
maturation with recognition of the following
stages: promegaloblast, basophilic megaloblast,
polychromatophilic megaloblast, orthochromatic
megaloblast.

MYELOID SERIES

MATURE ERYTHROCYTE
Biconcave disc with a central pale area that
gradually fades into reddish-pink cytoplasm.

NEUTROPHILS, EOSINOPHILS, BASOPHILS

RED BLOOD CELLS

Growth Factor: GM CSF (Granulocyte Monocyte

Colony Stimulating Factor)

G. NEUTROPHIL METAMYELOCYTE . From this

stage on, cytoplasmic changes are not significant.
Nucleus: indentation or flattening on one side
and begins to constrict, which is the chief
identification criterion; kidney or bean-shaped.
Nuclear Chromatin: condenses even more to
become coarsely clumped
Cytoplasm: uniformly pink with pinkish purple
secondary granules evenly distributed.
H. NEUTROPHIL BAND Partial constriction of the
nucleus occurs in this stage.
Nucleus: elongated, curved or sausage shaped
nucleus w/ no threadlike filament
Cytoplasm: stains light pink w/ numerous specific
granules that gives it a grainy appearance.
I. NEUTROPHIL SEGMENTED fine filament is
formed between two lobes. Cytoplasm contains 2x
as many specific granules than azurophil
granules.
Nucleus: segmented into 2-5 lobes connected by
a threadlike filament
Nuclear Chromatin: dark purple with densely
stained clumps
Cytoplasm: same as the band
J. EOSINOPHIL usually with bilobed nucleus with
moderately large, refractile cytoplasmic granules
that stain deep red or orange.
K. BASOPHIL shows large, coarse cytoplasmic
granules that stain deep blue; the granules may
be seen w/in the cytoplasm or overlying the large
irregular nucleus.
L. MAST CELLS are connective tissue of
mesenchymal origin that contains metachromatic
cytoplasmic granules. They are widely distributed
in the body (thymus, spleen, BM,etc) but not
normally seen in the blood. These are larger
basophils with low N/C ratio.

A. GM CFC: common progenitor cells for

granulocyte and monocyte & which under the
hormonal stimulation of GM-CSF divides and gives
rise to myeloblast.
B. MYELOBLAST earliest recognizable granulocyte
monocyte precursor
Size: 12-14 micrometers in diameter
Nucleus: high N/C ratio in which nucleus occupies
most of the cell leaving only a rim of cytoplasm;
nucleus is round & made up of smooth, delicate,
uniformly distributed chromatin patterns
Nuclear Chromatin: fine, uniform, delicate
Nucleoli: 2 or more nucleoli
Cytoplasm: pale, clear blue and without granules
The presence of azurophil granules in the
cytoplasm heralds the earliest promyelocyte
and indicates that the cell is to be a
neutrophil.
C. PROMYELOCYTE this stage of maturation
encompasses the entire period of production of
azurophil granules.
Size: cell slightly larger than myeloblast; 16-24
micrometers in diameter
Nucleus: nuclear chromatin begins to condense a
bit; N/C ratio decreases; round to oval in shape;
reddish blue
Nucleoli: less obvious & may not be visible
Cytoplasm: basophilic and begins to be filled
more & more by large, prominent, reddish purple
azurophil granules.
D. NEUTROPHIL MYELOCYTE begins with the
appearance of specific neutrophil granules; with
successive mitosis, the number of azurophil
granules diminished. Myelocytic stage is the last
stage capable of cell division.
Size of Neutrophil Myelocyte: 10-12
micrometers in diameter
Cytoplasm of Neutrophil: loses blue color and
shows pinkish-tan color
Nucleus of Neutrophil: round, becomes more
condensed and the chromatin pattern clumped
with 0-1 nucleoli.
Nucleus of Eosinophil: similar to neutrophils but
are larger with fewer nuclear lobes
Cytoplasm of Eosinophil: cytoplasmic granules
are large and take the basophilic stain in the early
stage. As the cell matures, the granules appear as
red-orange color.
Basophil: granules are larger than azurophil
granules of the promyelocyte stage and are often
irregular in shape. As the cell matures, the
granules become metachromatic (red-purple)
because of increasing acid mucopolysaccharide
content (heparin).
Nucleoli: usually absent
E. EARLY NEUTROPHIL MYELOCYTE has fine,
dispersed nuclear chromatin pattern; more
azurophil granules and fewer specific granules.
F. LATE NEUTROPHIL MYELOCYTE more
condensed chromatin pattern
Cytoplasm: more specific granules and fewer
azurophil granules

WHITE BLOOD CELLS

Leukocytes have nuclei and do not contain

hemoglobin.
N.V.: 6500 10,000 WBCs / mm3
When leukocytes reach their destination,
they leave the bloodstream by migrating
between the endothelial cells of the blood
vessels (DIAPEDESIS), enter the connective
tissue spaces, and perform their function.
Within the bloodstream, leukocytes are round; in
connective tissue, they are pleomorphic.
They generally defend the body against
foreign substances.
WBCs are classified as granulocytes which have
specific granules (neutrophils, eosinophils, and
basophils) and agranulocytes which lacks specific
granules (lymphocytes and monocytes). Both
granulocytes and agranulocytes possess nonspecific (azurophilic) granules, now known to be
lysosomes.
There are 3 types of granulocytes:
NEUTROPHILS, BASOPHILS & EOSINOPHILS
NEUTROPHILS a.k.a. Polymorphonuclear
leukocytes and the most numerous type of WBC;
they are avid phagocytes, destroying bacteria
that invade connective tissue spaces.

They are 9-12 micrometers in diameter and have a

multilobed nucleus. The lobes connected to each
other by slender chromatin threads, increase in
number with the age of the cell. In females, the
nucleus presents a characteristic small appendage,
the drumstick, which contains condensed,
inactive second X chromosome. It is also called the
BARR BODY or SEX CHROMOSOME but is not
always evident in every cell.

Cytoplasm: increasingly more pink than blue

Granules: great in number
D. MATURE MEGAKARYOCYTE giant cell
Nucleus: compact & highly lobulated with
multiple nuclei (up to 32) that usually remains
connected
Cytoplasm: abundant containing numerous
small, rather uniformly distributed granules with a
reddish-blue color
Chromatin pattern: linear & coarse with distinct
spaces between the strands
E. PLATELETS or thromboplastids; small, diskshaped, non-nucleated cell fragments derived
from megakaryocytes; dense blue to purple
particles with granules.
They display a peripheral clear region, the
hyalomere and a central darker region, the
granulomere.
Size: 2-4 micrometers in diameter
Plasmalemma: has numerous receptor
molecules as wells as a relatively thick glycocalyx
(15-20nm).
Life span: less than 14 days

SPECIFIC GRANULES Contains various

enzymes and pharmacological agents that aid the
neutrophil in performing its antimicrobial functions.
AZUROPHILIC GRANULES are lysosomes,
containing acid hydrolases, myeloperoxidase, the
antibacterial agent lysozyme, bactericidal
permeability-increasing (BPI) protein, cathepsin G,
elastase, and nonspecific collagenase.
TERTIARY GRANULES contain gelatinase and
cathepsins as well as glycoproteins that are
inserted into the plasmalemma.
MONOCYTES & MACROPHAGES

LYMPHOID SERIES

A. PROMONOCYTE The earliest recognizable cell

Nucleus: Oval, indented, fine with uniform
chromatin pattern
Nucleoli: 2-5 nucleoli
Cytoplasm: basophilic w/ ground glass
appearance; variable number of azurophil
granules.
B. MONOCYTE present in both blood & BM
Nucleus: large cell with slightly eccentric,
irregular and appears indented nucleus (kidneyshaped) & shows streaked chromatin patterns
Nucleoli: indistinct
N/C ratio: moderate to low
Cytoplasm: opaque with abundant fine
azurophilic granules

LYMPHOCYTES
Round cells but may be pleomorphic as they
migrate through connective tissue.
There are 3 types of lymphocytes:
T LYMPHOCYTES 80% of circulating lymphocytes
B LYMPHOCYTES 15% of circulating lymphocytes
NULL CELLS 5% of the circulating lymphocytes
A. LYMPHOBLAST
Nucleus: round, purple nucleus
Nucleoli: 1-2
Nuclear Chromatin: reveals delicate strands
that have a stippled or sieve-like appearance that
stains evenly and lightly
Cytoplasm: scant blue cytoplasm

MEGAKARYOCYTIC SERIES
B. LYMPHOCYTE
Size: somewhat larger than erythrocytes; 8-10
micrometers in diameter
Nucleus: slightly indented, round nucleus that
occupies most of the cell; is dense with a great
deal of hemachromatin and is accentrically
located.
Cytoplasm: peripherally situated and stains light
blue and contains a few azurophilic granules.

MEGAKARYOCYTES & PLATELETS

Platelets originate from the megakaryocytes, largest of
all the hematopoietic cells.
Growth Factor: MK CSF (Megakaryocyte Colony
stimulating Factor) which induces committed
progenitor cells to proliferate.
Thrombopoietin promotes differentiation and
maturation.

FUNCTIONS
ERYTHROCYTES responsible for the transport of
oxygen and Carbon dioxide to and from the tissues of
the body.

A. MEGAKARYOBLAST
Nucleus: compact (lobed)
Cytoplasm: stains basophilic
Granules: few are present
B. PROMEGAKARYOCYTE
Nucleus: horse-shoe shaped
Cytoplasm: has a pink center
Granules: starting to increase in number
C. GRANULAR MEGAKARYOCYTE
Nucleus: multi-lobed

NEUTROPHILS phagocytose and destroy bacteria

by using the contents of their various granules
(lysozymes, defensins, and strong oxidants such as
superoxide anion, H2O2, and hypochlorite anion).

EOSINOPHILS phagocytize antigen-antibody

complexes and to destroy parasitic infection; combat
effects of histamine in allergic reactions.

SIGNIFICANCE OF HIGH & LOW COUNT

BASOPHILS mediates in inflammatory responses

and involved in immediate hypersensitivity reaction.
Basophilic granules contains histamine, heparin,
peroxidase.

MONOCYTES Stay in the circulation for only a few

day then migrate through the endothelium of venules
and capillaries into the connective tissue, where they
differentiate into macrophages.

MACROPHAGES Phagocytose unwanted particular

matter, produce cytokines that are required for the
inflammatory and immune responses, and present
epitopes to T lymphocytes.

LYMPHOCYTES B cells which develop into plasma

cells are responsible for the Humoral-mediated
Immune system and secrete antibodies while T cells
are responsible for the Cell-mediated immune system
and attack invading viruses, cancer cells and
transplanted tissue cells. NK cells can kill some foreign
and virally altered cells without the influence of the T
cells.
PLATELETS releases chemicals that promote
vascular spasm and blood clotting; forms platelet plug
in hemostasis.
NORMAL VALUES
RBCs: Male 4.2 to 5.4 M cells / mm3

ERYTHROCYTOSIS increase RBC, Hct and Hgb;

decrease erythropoietin production
ERYTHREMIA decrease RBC, Hct & Hgb; increase
erythropoietin production
THROMBOCYTOPENIA decreased platelets and
leads to bleeding. Bleeding is generalized and
occurs from small vessels, resulting in purplish
splotches on the skin. This condition is believed to
be an autoimmune disease, in which Abs are formed
to ones own platelets and these Abs destroy the
platelets.
ANEMIA Decreased number of RBCs & Hgb
POLYCYTHEMIA increased number of RBCs & Hgb
INCREASED HEMOGLOBIN newborns, men,
people living at higher altitudes; polycythemia vera
and dehydration.
DECREASED HEMOGLOBIN adults, women,
people living at sea level, pregnancy; anemia and
leukemia.

WBC TYPE
NEUTROPHIL
S

HIGH COUNT
Bacterial
infection,
burns, stress,
inflammation,
appendicitis

LYMPHOCYTE
S

Viral infections
(mumps),
some
leukemias
Viral or fungal
infections, TB,
some
leukemias,
other chronic
diseases
Allergic
reactions,
parasitic
infections,
autoimmune
diseases,
asthma
Allergic
reactions,
leukemias
(chronic
granulocytic
leukemia),
cancers,
hypothyroidis
m

MONOCYTES

Female 3.6 to 5 M cells / mm3

HEMOGLOBIN: Male 13.5 to 18 g/dL
Female 12 to 16 g/dL
EOSINOPHILS

Infants 14 to 20 g/dL
WBCs: 5,000 to 10,000 cells / mm3
NEUTROPHIL SEGMENTED 60 to 70%
NEUTROPHIL BAND 2 to 6%

BASOPHILS

LYMPHOCYTES 20 to 25%
MONOCYTES 3 to 8%
EOSINOPHIL 2 to 4%
BASOPHIL 0 to 1%
PLATELETS 150,000 to 400,000 / ul

LOW COUNT
Radiation
exposure, drug
toxicity, Vit. B12
deficiency or SLE
(systemic lupus
erythromatosus)
Prolonged illness,
immunosuppress
ion, or treatment
w/ cortisol
Bone Marrow
suppression,
treatment w/
cortisol
Drug toxicity,
stress

Pregnancy,
ovulation, stress
or
hyperthyroidism