Chapter 19

The Blood
Learning Objectives
By the end of this chapter you should be able to:
 Describe the functions and constituents of the blood
 Describe the origin and process of formation of blood components
 Describe the structure, function, life cycle and production of red
blood cells and white blood cells
 List and explain the mechanisms that contribute to hemostasis and
factors that promote or inhibit clotting
 Differentiate between ABO and Rh blood groups and why matching
donor and recipients is important
 The Blood

 The cardiovascular system consists of three

interrelated components: Blood, the heart, and
blood vessels. The focus of this chapter is blood;
the next two chapters will examine the heart and
blood vessels
 Hematology is the branch of science concerned
with the study of blood, blood-forming tissues and
the disorders associated with them
 Components of Blood
 Blood is a liquid connective tissue consisting of cells surrounded by a liquid extracellular matrix ( called blood
plasma) suspends various cells and cell fragments.
-Blood transports oxygen from the lungs and nutrients from the
gastrointestinal tract, which diffuse from the blood into the interstitial
fluid and then into body cells. Carbon dioxide and other
wastes move in the reverse direction, 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.
If a tube of anticoagulated blood is allowed to sit for a period of time, the cellular portion
will precipitate out of
solution and form a heavier
sediment below the
straw-colored liquid
plasma
 Used for determining a
persons hydration level
 The Blood
Blood has three functions:
1. Transportation - respiratory gasses (oxygen and carbon dioxide),
nutrients and wastes, heat, and hormones to and from your body's cells.
2. Regulation - It helps regulate body pH and temperature, and blood
osmotic pressure influences water content in cells-It makes sure we
have enough water in individual tissues sure, So we don't get dehydration
of blood cells or shrinkage, or swelling.
3. Protection – against excessive loss by clotting mechanisms( blood can
clot becomes gel like and protects against excessive loss from
cardiovascular system after an injury). and immune defenses against
infection by white blood cells.
 Components of Blood
 Males have a blood volume of approximately 5-6 liters and
females approximately 4-5 liters
 Composed of CT cells (45%) suspended in a salt-water-and-
protein solution called blood plasma (55%)
• It is viscous (thick) and more

dense than water and has a

slightly alkaline pH (7.35-7.45)
Components of Blood
Substances in Blood Plasma
 Formed Elements
Red blood cells (RBCs) make up the bulk of the blood cells, with
many fewer white blood cells (WBCs) interspersed in among them
• The normal RBC mass is between 38–46% by volume for the

average adult
female and 40-54%
for the average
male – this is called
the hematocrit (Hct the
Percentage of total blood
Volume occupied by RBC)
 Formed Elements
• RBCs outnumber WBCs by about 700:1

• There are 5 different types of WBCs, all with varying functions

 Formed Elements
Platelets are more numerous than WBCs, but they have a
short life span (5 to 9 days) and they are remnants of cells.
They don't have much mass. They appear as little specks (no
nucleus) interspersed among the many red cells
• Their granules

contain chemicals that,

once released, promote
blood clotting
 Hematopoiesis
 the formation of blood elements is called hemopoiesis
(hematopoiesis).
 Occurs in the embryo yolk sac, then the liver, spleen, and thymus of a
fetus
 It occurs in the red bone marrow just before birth and throughout
life means once we are born we only have RBM and then
throughout life we form WBC and platelets.
 Red bone marrow – highly vascularized connective tissue between
trabeculae in spongy bone. From red bone marrow we can form all
type of cells including WBC, RBE and platelets.
 found in bones of axial skeleton, pectoral and pelvic girdles and the
 Erythropoiesis
Erythropoiesis is the part of hematopoiesis that deals with the
production of RBCs. There has to be some type of signaling in order for it
to produce RBC. Erythropoiesis increases when states of hypoxia (O2
deficiency) stimulates the kidneys to release the hormone.
When body needs the production of RBC,
There is a stimulation of the kidneys to release
A hormone called erythropoietin (EPO)
• EPO circulates in the blood until it gets

• to the red marrow and speeds up

the maturation of cells and release of

immature red blood cells
 Red Blood Cells
 Red blood cells (aka erythrocytes) are bi-concave discs.
 Mature RBCs don't have a nucleus or any protein making machinery and
are destined to die in about 120 days. After they die, they are recycled
again.
 In a sense they are not really cells, but
remnants of cells with a very specific
purpose – to carry O2 to the tissues of
the body. Destruction and production of
the cells are in balance. If the RBC that
are destroyed more than produces, this
is a disorder, and we usually have
release Erythropoietin to increase our
RBc by maturing more RBC.
 Reticulocytes
The rate of erythropoiesis is measured by the number of immature
RBCs (called reticulocytes or “retics”) in the peripheral circulation.
Immature RBc takes them 1 to 2 days to become mature.
• A low reticulocyte count (<.5%) indicates a low rate of

erythropoiesis which is a low rate of producing RBC – due to

problems with EPO production or deficiency of red bone marrow
• An elevated rate (>2%) indicates a high rate of erythropoiesis –

often the result of blood replacement, iron therapy or EPO

injections
 Red Blood Cells
 Regulation of RBC production
through negative feedback
 Disruption resulting from
decreased oxygen delivery
stimulates the increase in
circulating reticulocytes
 More oxygen delivery to
tissues stops higher than
normal production
 Red Blood Cells
 The characteristic RBC shape increases the cell surface area and
gives them a high oxygen carrying capacity.
 Lack a nucleus so when mature are unable to divide( Mature
RDB cells don't have a nucleus so they can't divide).
 Because they lack mitochondria, they don't use any of the
oxygen they carry to make AtP – they produce ATP anaerobically
• Their shape also allows them to deform and fit in small

capillary beds and squeeze through narrow channels in the

spleen and capillaries
 Hemoglobin
Hemoglobin (Hgb) is a protein molecule adapted to carry O2 (and CO2 as well),
and each RBC contains 280 million molecules of Hgb
• A Hgb molecule consists of 4 large globin proteins (2 alpha and 2 beta
chains), each embedding an iron-containing
heme center.

Mature RBC are still

Call Eukaryotic
Even if they don’t
have a nucleus
because precursor
Cells immature cells
still have a nucleus
 Red Blood Cells
 Hemoglobin is involved in regulating blood flow and blood
pressure via the release of nitric oxide (NO)
• NO causes vasodilation, which improves blood flow and
enhances oxygen delivery
 Red blood cells also contain carbonic anhydrase, which
catalyzes the conversion of carbon dioxide and water to
carbonic acid
• Carbonic acid transports about 70% of carbon dioxide in the
plasma
 Abnormalities of Erythropoiesis
 Anemia is a condition of reduced oxygen carrying capacity of the
blood. Due to insufficient RBC’s or hemoglobin (quality or quantity)
• It is most often the result of low iron intake( Iron is attached to

hemoglobin), hemolysis( bursting of RBC), autoimmune disease,

blood loss, or lack of production in the bone marrow
 Polycythemia is a condition of excess number of RBCs
• It occurs in response to hypoxia (natural “blood doping” is

training at high altitude), shots of EPO (illegal “doping”), smoking

(COPD), or dehydration. More mature rBC are produced.
 Anemias
 Iron deficiency anemia is the most common anemia in the
U.S., and affects primarily menstruating women
• In the United States, 20% of all women of childbearing

age have iron deficiency anemia, compared with only 2%

of adult men
 Hemorrhagic anemia is the result of precipitous blood
loss, and results in an equal decrease in Hct, Hgb content,
and RBC count
 Anemias
Sickle-cell disease (SCD), also called sickle-cell anemia, is an autosomal recessive disorder. A
genetic defect in the primary DNA sequence leads to production of a faulty Hgb and RBCs
that take on a rigid, sickle-shape( It has to do with that your DNA having incorrect nucleotide,
you have incorrect AA in hemoglobin protein, and that results in less oxygen and results
in wrong shape of cell
 Sickling decreases the cells' flexibility

 increasing the chance of rupture.

 Erythropoiesis

cannot keep up with hemolysis,

leading to anemia( Sickle cells they can stuck
easily , can easily clot , there is less stability of
the cell; they can't make their way to vessels ,
and you get more breaking down of cells that
producing
 RBC Life Cycle
RBCs live only about 120 days. To maintain normal numbers,
new mature cells must enter the circulation at the rate of at
least 2 million/second, a pace that balances the equally high
rate of RBC destruction
• Ruptured RBCs are removed from circulation and destroyed
by macrophages( type of white blood cells) in the spleen
and liver and red bone marrow—the breakdown products
are recycled and used in numerous metabolic processes,
including the formation of new RBCs
 from transferrin and transferred to Ferritin
in liver.. Once we need we get that iron
attached to transferrin again and transferred
to Red bone marrow. When it’s incorporated
into a new RBC. . Then we have
erythropoiesis in red bone marrow and the
release of iron as a new RBc entering the
circulation
 Leukocytes
Unlike RBCs, white blood cells (WBCs) or leukocytes have
nuclei and a full complement of other organelles - but they
do not contain the
protein Hgb
 WBC Indices
For diagnostic purposes, physicians measure the total number of
circulating WBCs
• A leukocytosis is any WBC count > 10,000/micro litre( above the
limit), and usually indicate an infection, surgery or strenuous
exercise( something that causes stress on the body). It's prompting
our immune system to reponds
• A leukopenia is any WBC count < 5,000/micro litre( something
causing your immune system not responding properly, and they
can't function properly), and usually indicates a severe disease
(AIDS, bone marrow failure, severe malnutrition, or chemotherapy)
 WBC Indices
To enhance the diagnostic value of a WBC count, the
percentages of each of the 5 types of WBCs is determined
by using a machine to do a statistical analysis of the blood
sample. This is called the WBC differential
 WBC Indices
Shifts in the normal percentages of circulating WBCs will often
point towards a bacterial infection (elevated percentage of
neutrophils) or a viral infection (elevated percentage of
lymphocytes
• In this peripheral blood smear

a patient with lymphocytic

leukemia has a WBC >150,000
and 90% of the WBCs are
cancerous lymphocytes!( that
Lymphocytic leukemia.
means we have viral infection).
WBC Indices
Formed Elements of the Blood
Formed Elements of the Blood
 Hemostasis
Hemostasis is a sequence of responses that stops bleeding( blockage of any tube
system that has blood loss). The blood that's circulating in body should always be in
the tubing system)
• When blood vessels are damaged or ruptured, the hemostatic response must be
quick, localized to the region of damage, and carefully controlled in order to be
effective. When we have damage in blood vessels, we need to use medical
assistance or the body homeostasis can repair it and stops that leaking of blood
from happening.
• Three mechanisms reduce blood loss
1. Vascular spasm

2. Formation of a platelet plug ( temporary blockage of the gap that we lose

blood through).
3. Blood clotting (coagulation)
 Hemostasis
1. Vascular spasm occurs as damaged blood vessels constrict. If we have damage, this
is an immediate
response, it narrows
down the vessel to narrow
down the amount of
blood that's getting to the
space where there is a breakage

2-Platelets adhere to damaged

endothelium to form a
platelet plug( Because we have platelets
circulating in our blood, we get platelets
sticking to that damage inner layer epithelial
tissue. These platelets tat are sticking together
for a plug. When platelet encounters a place where
there is a breakage usually there is. These platelets
bridge that break down
Platelet Plug
Red blood cell

Platelet

Formation, platelets
secretes ions, and Collagen fibers
and damaged
endothelium

other substances to 11 Platelet adhesion

form a blockage for the

damaged vessel. Also
we have ADP to have Liberated ADP,
serotonin, and
thromboxane A2

more platelet. The

22 Platelet release reaction

blocking damaged of
blood vessel here is
temporary.
Platelet plug
 Hemostasis
3. Clotting (coagulation) is possible because of the presence of several clotting
proteins normally dissolved (soluble) in the blood. Coagulation occurs in a
cascading fashion whereby one activated clotting protein triggers the next
step in the process, which triggers the next, and so on - once activated,
the soluble clotting factors
become insoluble. It's a
perminant solution. So it becomes
gel like and mix with protein threads,
they form a mesh network and form a
block on the vessel breakage to
prevent blood leaking out.
• There are 2 pathways to
activate the system
 (a) Extrinsic pathway (b) Intrinsic pathway

Tissue trauma Blood trauma

Stages Damaged
endothelial cells
expose collagen
fibers

of Tissue
factor
(TF)

Clotting Damaged
platelets

. Also Ca2+
Activated XII

Ca2+
Activated
platelets

Calcium
+
Platelet
phospholipids

is V
Activated X Activated X

Ca2+ Ca2+
V +

importa
PROTHROMBINASE
(c) Common
pathway

Ca2+

nt for Prothrombin
(II)
THROMBIN
Ca2+
XIII
2

blood Fibrinogen
(I)
Loose fibrin
Activated XIII
STRENGTHENED 3
threads FIBRIN THREADS

clotting.
 Hemostasis
 The extrinsic pathway has few steps
and occurs rapidly, often within
seconds, once the protein “tissue
factor” (TF) leaks into the blood
 The intrinsic pathway is more
complex and occurs more slowly in
response to damage to endothelial
cells or phospholipids released by
activated platelets
 Hemostasis
Both the extrinsic and intrinsic clotting pathways converge at
a common point (pathway) where factor X becomes
activated (Xa)
• In this second stage of
blood clotting prothrombin
is converted to thrombin
which in turn converts
soluble fibrinogen to
insoluble fibrin threads
 Hemostasis
 The mineral Ca2+ plays an important role throughout the clotting
system( activation of protiens), and many steps have positive or negative
feedback on various other steps to propagate the process, yet maintain control
 Clot retraction( happens after the clotting blood and the blocking of blood
leakage) is the consolidation of the fibrin clot. As the clot retracts as platelets
pull on the fibers, it pulls the edges of
the damaged vessel closer together,
decreasing the risk of further
damage – new endothelial cells can
then repair the vessel lining( complete
reforming of the vessels that had damage). Then clot will be broken down and
destroyed and vessel is
repaired completely..
 Fibrinolysis
Because blood clotting involves amplification and positive feedback
cycles, a clot has a tendency to enlarge, creating the potential for
impairment of blood flow through undamaged vessels ( the process
of breaking down the clots by enzymes, once repair has happened
and to encourage the blood continuation through that blood vessel)
• The fibrinolytic system dissolves small, inappropriate clots; it
also dissolves clots at a site of damage once the damage is
repaired
• Both body tissues and blood contain substances that can
activate plasminogen to become plasmin, (the enzyme that
actively dissolves clots)
 Intravascular Clotting
( Unexpected clots forming) Blood clots sometimes form
unexpectedly within the cardiovascular system. Clotting in an
unbroken blood vessel (usually a vein) is called thrombosis;
the clot itself, called a thrombus
• Such clots may be initiated by roughened endothelial
surfaces of a blood vessel resulting from atherosclerosis,
trauma, or
infection
 Intravascular Clotting
A thrombus may become dislodged and be swept away in the
blood. When a blood clot, air bubble, piece of fat or other
debris is transported by the bloodstream,
it is ga
blood vessel and cause ischemia to
the tissue beds distal to the obstruction
 Intravascular Clotting
 Intravascular clots may also form when blood flows too
slowly (stasis), allowing clotting factors to accumulate
locally and initiate the coagulation cascade
 Having an undamaged blood vessels with smooth surfaces,
good circulation, and non-sticky platelets are important
factors that inhibit thrombosis
• Administration of anticoagulants and platelet inhibiting

drugs (aspirin-like drugs) can also hinder thrombus

formation or reverse a thrombus that has formed
Hemostasis
 Blood Groups
Red cells (and all cells in the body) have proteins on their surface
which act as antigens or surface markers( those two help us
determining the characteristics of our blood).
• Even within the same species, the antigens of one individual
are not necessarily compatible with those of another. For this
reason, before donor blood cells can be transfused to another
person the major surface antigens must be determined
• The most significant of the 100 markers currently known to
exist on RBCs are the A and B antigens( Allow us to
determining our blood grouping ABO).
 Blood Groups
 In transfusion medicine the presence or absence of the
A and B red cell antigens forms the basis of the ABO blood
group system

Another major red cell antigen is the Rh antigen( RH + means

you have a surface antigen, and RH- means you don’t have),
which 85% of the population have, and comprises another
 Blood Groups
For reason that are not totally clear, serum contains anti-ABO
antibodies of a type opposite to the ABO antigen on the red
cell surface
• For instance, those with A antigens on their red cells
have anti-B antibodies in their serum
 Blood Groups
By knowing the status of the A antigen, B antigen, and Rh antigen,
most of the major blood incompatibility issues can be avoided
• Type AB individuals are “universal recipients” because they has

neither anti-A nor anti-B antibodies in their serum that would

destroy transfused RBCs( AB people can receives all type of
blood, A, B, O and AB).
• Type O individuals are “universal donors” because their RBCs

have no antigens on the cell surface that can potentially react

with the recipients serum( You won't get any clotting
happening).
 Blood Groups

Blood typing for ABO status is

done using single drops of blood
mixed with different antisera
• Agglutination with an antisera
indicates the presence of that
antigen on the RBC
 Transfusion Reactions

In a blood transfusion, if the recipient receives the wrong

blood type, antigen-antibody reactions will cause a rapid
destruction (hemolysis) of the donor red blood cells
• Giving the wrong type blood can cause the patient to
develop a fever, develop serious renal failure, or go into
shock. The most common cause is clerical error (i.e. the
wrong unit of blood being given to the patient)
 Rh Incompatibility
Normally, blood plasma does not contain anti-Rh antibodies.
Individuals whose RBCs have the Rh antigen are said to be Rh+
while those who lack the Rh antigen are Rh-
• Rh incompatibility can cause problems with any
blood transfusion, so it is screened just as carefully as the ABO
group( if a person with RH+ blood gives to a person with RH -,
then we will have RH antibody in this case but it's dangerous)
Perhaps the biggest problem with Rh incompatibility, however,
involves mother and child in pregnancy
 Rh Incompatibility
If blood from an Rh+ fetus sensitizes an Rh- mother during birth,
anti-Rh antibodies will form in the blood of that woman. ( usually
happens in the second pregnancy not the first) During her next
pregnancy those antibodies can cross the placenta to affect the
next baby if it is Rh+
• Hemolytic disease of the
newborn (HDN) results
when an Rh+ fetus
develops in the womb
of an Rh- woman
 Rh Incompatibility
To prevent HDN, mothers who are Rh- are given a injection
of RhoGAM - a commercially produced anti-Rh antibody –
at various points in her pregnancy (just before and after
delivery)
• The administered RhoGAM destroys any Rh+ antigens
from the baby before the mother's immune system can
become sensitized to them and produce her own anti-
Rh antibody. For this same reason, RhoGAM is given to
Rh- patients who have miscarriages