Blood Cells

Blood cells are

formed in the bone
marrow.
All blood cells arise from
the same bone marrow stem
cells.
Stem cells are immortal,
meaning they never die (at
least not until you do).
Stem cells are also
undifferentiated. meaning
they have not yet developed
into a particular cell type.
Furthermore, stem cells are
pluripotent, meaning they
have the potential to become
any type of blood cell.
These immortal,
undifferentiated,
pluripotent stem cells give
rise to erythrocytes,
leukocytes and platelets.
The diagram below
illustrates the different
types of blood cells.
Leukocytes, also known as
white blood cells, are a
group of related cell types
that involved in immune
function. Leukocytes
include neutrophils,
eosinophils, basophils,
lymphocytes and
monocytes.
Erythrocytes
Erythrocytes,
also known as
red blood cells
(RBCs),
function to
transport
oxygen in the
blood. The
shape of
erythrocytes is
ideal for this
function. Seen
from the top,
erythrocytes
appear to be
circular, but a
side view
shows that
they are
actually
biconcaved
discs. This
shape
increases the
surface area-
to-volume
ratio of the
cell, thus
increasing the
efficiency of
diffusion of
oxygen and
carbon dioxide
into and out of
the cell.
Erythrocytes
also have a
flexible plasma
membrane.
This feature
allows
erythrocytes,
which have a
7m diameter,
to squeeze
through
capillaries as
small as 3m
wide.
Erythrocytes
contain
tremendous
amounts of
hemoglobin,
the protein
that binds
oxygen. In
order to make
room for more
hemoglobin to
carry more
oxygen,
erythrocytes
loose their
nucleus and
other
organelles as
they develop in
the bone
marrow.
Because they
lack a nucleus
and other
cellular
machinery,
erythrocytes
cannot repair
themselves
when
damaged,
consequently
they have a
limited life
span of about
120 days. The
removal of old
and dying
erythrocytes is
carryied out
by the spleen.
Erythrocytes,
which
represent the
most
numerous cell
type in the
body die at a
rapid rate, 2-3
million
erythrocytes
die every
second.
Erythrocyte
production
must equal
erythrocyte
death or the
cell population
would decline.
Erythrocytes
are produced
through a
process called
erythropoesis.

Erythropoesis
The body must have a way
to assess the concentration
of erythrocytes in the blood
such that erythrocytes are
produced at a rate that
matches the body's needs.
The regulation and
production of RBCs is called
erythropoesis. The
mechanism of erythropoesis
occurs in the following way.
The kidney monitors the
level of oxygen in the blood.
If oxygen levels are low then
the kidney secretes a
hormone called
erythropoetin.
Erythropoetin enters the
blood stream and travels
throughout the body. All
cells are exposed to
erythropoetin, but only red
bone marrow cells, which
have erythropoetin
receptors, respond to the
hormone. Erythropoetin
stimulates the production of
erythrocytes in the bone
marrow. These erythrocytes
leave the bone marrow and
move into the blood stream.
As the erythrocyte
population increases, the
oxygen carrying capacity of
the blood increases. When
the kidney senses that
oxygen levels are adequate,
it responds by slowing the
secretion of erythropoetin.
This negative feedback loop
ensures that the size of the
erythrocyte population
remains relatively constant
and that the oxygen carrying
capacity of the blood is
always sufficient to meet the
needs of the body.
The gene encoding
erythropoetin was recently
cloned by a local biotech
company (Amgen).Through
recombinant DNA
technology erythropoetin is
now produced in large
quantities and is available
for clinical use.
Clinical uses of recombinant
erythropoetin include:
1. It is used to boost
erythrocyte production
prior to surgery as a way
to decrease the volume of
 transfused donor blood
required.
2. Its is used to boost
erythrocyte production
following chemotherapy
for cancer.
Chemotherapy targets
fast growing cells.
Cancer cells are fast-
growing and therefore
die, but erythrocytes,
which are also fast
growing cells, suffer
decline following
chemotherapy.
Hematocrit
Whole blood is
composed of
plasma (liquid),
cells and platelets.
If whole blood is
placed into a tube
and centrifuged,
the cells and the
plasma will
separate. The
erythrocytes,
which are heavy,
will pack into the
bottom of the
tube, the plasma
will be at the top
of the tube, and
the leukocytes
and platelets will
form a thin layer
(buffy coat)
between the
erythrocytes and
the plasma. The
hematocrit is
defined as the
percentage of
whole blood made
up of
erythrocytes. This
value is
determined by
dividing the
height of the
erythrocytes by
the total height of
the blood in the
tube and
multiplying by
100.
Hematocrits vary depending
on sex and environmental
conditions, but there is a
range of values that is
considered normal. Average
hematocrit values are:
 males.......... 40-50%
 females....... 38-45%
 athletes........ > 50%
Any activity or condition
that consistently lowers
oxygen levels in the blood
will cause an increase in
erythropoesis and a
subsequent rise in the
hematocrit.
Factors that will raise the
hematocrit include:
 Exercise. During aerobic
exercise blood oxygen
levels are lowered due to
rapid consumption of
 oxygen by active skeletal
muscle. This stimulates
an increase in
erythropoesis, which
increases hematocrit,
which increases the
oxygen carrying capacity
of the blood. Thus
regular aerobic exercise
raises the hematocrit.
 Living at high altitude.
The air is thinner at
higher altitude, therefore
fewer molecules of
oxygen enter the lungs
with each breath. Oxygen
levels in the blood are
lower when breathing
such thin air. A person
that moves from Santa
Barbara, which is at sea
 level, to Denver,
Colorado, which has an
altitude of 5000', will
experience a rise in
hematocrit as
compensatory response
to the thin air.
 Injection of
recombinant
erythropoetin. Some
endurance athletes use
erythropoetin (illegally)
to increase their
hematocrit as a way to
increase stamina.

Primary
Polycythemia
Primary polycythemia is a
condition that is
characterized by an excess
of circulating erythrocytes
and an elevated hematocrit.
This condition is caused by a
tumor-like condition of the
bone marrow resulting in
over-stimulation of
erythropoesis. The
hematocrit raised as high as
high as 70-80%. The
increase in blood viscosity
assiciated with very high
hematocrits causes sluggish
circulation (lowering
delivery of oxygen to
tissues) and high blood
pressure.

Anemia
Anemia is a condition that is
characterized by a reduction
in the oxygen carrying
capacity of the blood. This
reduction is caused by
inadequate levels of
hemoglobin, inadequate
numbers of erythrocytes
(low hematocrit) or both.
Symptoms of anemia are
variable, but may include:
1. Fatigue. One of the
most common and
debilitating symptoms of
anemia is fatigue (lack of
energy), particularly with
exercise. Oxygen is
required to metabolize
fuel molecules (sugars,
fats and proteins) to
obtain energy. A person
with a low hematocrit
cannot carry enough
 oxygen in the blood to
meet their energy
demands.
2. Increased heart rate.
The body increases heart
rate to compensate for the
low oxygen carrying
capacity of the blood. If
more blood is moved
faster through the tissue
then tissues get more
oxygen per unit time.
3. Shortness of breath.
An anemic person may
feel short of breath and
then breath faster to
alleviate the feeling. This
is a compensation for the
poor delivery of oxygen
to the tissues.
4. Low blood pressure.
 The viscosity of the
blood drops as the
hematocrit decreases. A
decrease in blood
viscosity directly lowers
total peripheral resistance
(TPA) to the flow of
blood, thus lowering
mean arterial blood
pressure (MAP).
5. Pale Skin.
Hemoglobin is bright red
when oxygenated and
less red when
deoxygenated. Because
the redness of skin is due
to the redness of blood,
the skin of an anemic
person (who has less
oxygen in the blood) will
less red (paler) than the
 average person.
Causes of Anemia
As mentioned earlier,
anemia is characterized by
either low hemoglobin, low
hematocrit, or both. There
are several situations that
can lead to this state. The
causes of anemia include:
1. Dietary deficiencies
of iron, vitamin B12 or
folic acid.
2. Hemorrhage
3. Hemolysis
4. Bone marrow failure
5. Kidney disease
Dietary deficiencies
 Iron is required for the
production and function
of hemoglobin. In the
 absence of adequate iron,
hemoglobin production
slows down. Low
hemoglobin can lower
the hematocrit.
 Vitamin B12 and Folic
Acid are required for
DNA synthesis prior to
cell division. In the
absence of these nutrients
production of
erythrocytes is reduced.
The hematocrit is low
and many erythrocytes
are huge, fragile cells
called macrocysts. B12
deficiency can be caused
by a lack of intrinsic
factor, this is called
pernicious anemia.
Intrinsic factor, which is
 produced in the stomach,
is required for efficient
absorption of B12 out of
the small intestine and
into the blood.

Hemorrhage refers to a
significant loss of blood
through bleeding.
Hemorrhagic anemia is due
to blood loss that is greater
than the rate at which
erythrocytes can be replaced.
Blood loss may be due to
injury, donating blood,
ulcers, heavy menstruation,
etc.
Hemolysis refers to the lysis
(breaking) of erythrocytes.
Hemolytic anemia is due to
a high rate of erythrocyte
lysis in the blood stream.
Sickle cell anemia, which is
caused by defective
hemoglobin, is a genetic
form of hemolytic anemia.
Under conditions of low
oxygen (as during exercise)
the hemoglobin within
erythrocytes crystallizes.
This causes the RBCs to
adopt a sickled shape, which
makes them fragile and
easily lysed.
Bone marrow failure leads
to a reduction in the
production of erythrocytes.
This may be due to cancer or
toxic drugs.
Kidney disease can lead to a
reduction in the synthesis of
erythropoetin, resulting in a
low hematocrit.

(Revised Table of
October 11 contents Quiz
1999)