THE CARDIOVASCULAR SYSTEM
against disease
BLOOD
 the “river of life”
 it functionally connects the different
body organ systems
HEMATOLOGY
 branch of science concerned with the
study of blood, blood-forming tissues &
the disorders associated with them
FUNCTIONS OF BLOOD
1. TRANSPORTATION
o Delivers O2 from the lungs to the
cells
o Moves CO2 from the cells to the
lungs
o Carries nutrients, waste products,
hormones & other substances to
various destinations.
2. REGULATION
o Helps to maintain a steady PH (7.35-
7.45)of body fluids
3. TEMPERATURE
o Distributes heat, thereby adjusting
body temperature
1. Blood Vessel Dilates
(VASODILATION)
2. Heat Loss across the
epidermis increases
3. Blood Vessel Constricts
(VASOCONSTRICTION)
4. Heat loss across the epidermis
decreases.
4. PROTECTION
o In response to injury, it coagulates or
forms seals called clots, thereby
preventing blood loss & maintaining
cardiovascular function.
o Its WBCS protect against disease by
ingesting invading bacteria &producing
antibodies
o Also contains proteins that protect
CHARACTERISTICS OF BLOOD
1. Amount
 Ave. Volume: 4 to 6 l [varies
depending on person’s size, with
males having a higher blood
volume than females]
 Constitutes 20% of the ecf
 Approx. 8% of one’s body wt.
 Varies depending on amt. Of o2
2. Color
 Scarlet or bright red = arterial
blood (oxygen-rich)
 Dull red = venous blood (oxygen-
poor)
3. Ph
 Slightly alkaline
 7.35 to 7.45 = normal ph of blood
 Venous blood = is normally more
acidic (lower ph) than arterial
blood
4. Viscosity
 3 to 5 times denser/thicker than
water
 Viscosity = refers to the thickness
or stickiness of a substance
 The lesser the plasma/water
content, the more viscous blood
becomes
5. Temperature
 38°C = about 1°C warmer than
your core body temp.
COMPONENTS OF BLOOD
1. PLASMA
 makes up 55% of blood
 the liquid component
2. FORMED ELEMENTS
 the cellular elements
  make up 45% of blood
Comprise the following:
a) Red blood cells (RBC)
b) Buffy coat
 A thin, gray layer between the
Plasma and RBC
 Contains white blood cells (WBCs)
& platelets (PLTs)
c) PLASMA
 Color: pale yellow (straw-colored)
 Consistency: sticky
Consists of:
i. 91% water;
ii. 7% plasma proteins; &
iii. 2% other solutes
PLASMA
Components of Plasma
1. WATER
 acts as a solvent where different
substances are dissolved
2. PLASMA PROTEIN
a) Albumin
o The white of the egg
o Also synthesized in human
liver
o Most abundant plasma
protein
 Contributes to the colloid osmotic
pressure of blood, which pulls fluid
from the tissues to the blood in the
capillaries,thereby maintaining
normal blood volume & blood
pressure
b) Globulins
o are synthesized by the liver
o have various functions
depending on specific type
Types of Globulin:
 Alpha & beta globulins
 are synthesized by the liver
 have various functions
depending on specific type
HEMOPOIESIS
 Gamma globulins
also called “antibodies” or
“immunoglobulins”;
produced by the
LYMPHOCYTES; initiate the
destruction of pathogens &
provide us with immunity
c) Fibrinogen
d) Also synthesized by the liver
e) A clotting factor (plays an
essential role in blood
coagulation)
3. Other Solutes
o Electrolytes(Na+, K+, Cl–)
o Nutrients(products of digestion
such as amino acids, glucose,
fatty acids, vitamins & minerals)
o Respiratory gases (O2, CO2)
o Regulatory
substances(hormones, enzymes)
o Waste products(urea, uric acid,
creatinine, bilirubin, ammonia)
FORMED ELEMENTS
• collective term for the RBCs, WBCs &
PLTs
• specific breakdown is as follows:
• RBCs or erythrocytes
• PLTs or thrombocytes
• WBCs or leukocytes
(have various types; they are ordered
from most abundant to least abundant)
 Neutrophils(Granulocyte)
 Lymphocytes(Agranulocyte)
 monocytes(Agranulocyte)
 eosinophils(Granulocyte)
 basophils (Granulocyte)
• FORMED ELEMENTS are all created in
the red bone marrow & are derived
from a single population of stem cells.
 • also called “hematopoiesis”
• the process of the formation &
development of the formed elements of
blood
Hemocytoblast :
• or “hemopoietic stem cell”
• resides in the red bone marrow
• it has the capacity to differentiate
into many different types of
blood cells
• the primary stem cell where all
the formed elements arise
• also divides into similar daughter
cells to ensure its steady supply
throughout our lifespan
Red bone marrow :
• a highly vascularized tissue
located in the microscopic spaces
between the trabeculae of spongy
bone tissue
GROWTH FACTORS
• are several hormones w/c regulate the
proliferation & differentiation of
particular blood cells
• example: erythropoietin
Steps In Hemopoieses :
1. In response to growth factors,
hemocytoblasts produce two
secondary stem cells namely myeloid
stem cells & lymphoid stem cells
2. Myeloid stem cells begin their
development in red bone marrow &
give rise to immature cells. Growth
factors influence their maturation.
Once they mature, they then exit the
bone marrow & become rbcs, plts,
monocytes, neutrophils, eosinophils,
& basophils
3. Lymphoid stem cells begin their
development in red bone marrow
but complete it in lymphatic tissues;
they give rise to mature
lymphocytes.
RED BLOOD CELLS (RBCs)
• or erythrocytes
• the most abundant formed element in
the blood
• n° RBC count: 4.5 to 6 million cells per
cubic millimeter (mm3 or μL) of blood
Hematocrit (Hct):
• refers to the percentage occupied by
RBCs in the blood relative to plasma
• n° range: 38% to 48%
 an elevated Hct, w/c can occur
when one is dehydrated,
indicates  percentage of
RBCs due to the  plasma
volume
 since RBCs primarily
determine the viscosity of
blood, an increased Hct
increases blood viscosity
Structure Of Mature Rbcs:
o shape: biconcave disc or flattened w/ a
depressed center [this shape increases
the cell’s surface area making it suitable
for gas exchange]
o their plasma membrane is smooth &
flexible w/c allows them to deform w/o
rupturing as they squeeze through
narrow capillaries
o they are ANUCLEATE (do not have a
nucleus) & have no organelles
o they can neither divide nor carry out
extensive metabolic activities [thus, they
do not use up the O2 they carry making
them efficient O2 transporters]
o their cytoplasm is packed with
o HEMOGLOBIN- they stain pink or
orange-pink in a blood smear since their
hemoglobin attract the eosin dye found
in Wright’s stain
HEMOGLOBIN (HGB):
• the red pigment w/c occupies the
cytosol of RBCs & gives their color
• an iron-based protein that binds most of
the O2& a small portion of the CO2&
allows the RBCs to transport these gases
through the blood
• n° range: 12-18 grams per dL or
per 100 mL of blood
•  HGB levels indicate  O2-
carrying capacity of the blood
a) oxyhemoglobin: formed when HGB is
exposed to O2esp when RBCs pick up O2
in the pulmonary capillaries from the
lungs; gives arterial blood a bright red
appearance
b) carboxyhemoglobin: formed when HGB
is exposed to CO2esp when RBCs pick up
CO2 in the systemic capillaries from the
tissues; since little or no O2 molecules
are bound to it, that’s why venous blood
appears dull red
ABNORMALITIES:
ANEMIA
• medical term for a deficiency of
mature RBCs &/or HGB in circulating
blood
• lab tests reveal a RBC count, HGB
&/or Hct
POLYCYTHEMIA
• medical term for elevated RBCs in
circulating blood
• lab tests reveal an RBC count,
HGB &/or Hct
RED BLOOD FORMATION
ERYTHROPOIESIS
o The process of forming & developing
rbcsfrom hemocytoblasts (stem cells/
unspecialized cells) which differentiate
into erythrocytes (specialized cells) in
response to hemopoietic growth factors
o Involves the transformation of
hemocytoblasts into different
developmental stages of immature
rbcsin the red bone marrow
o Duration of erythropoiesis: 5-9 days
Immature RBCs
 are precursors of erythrocytes w/c
possess cellular organelles & thus have
the ability to divide & synthesize
proteins such as HGB
 lose their cellular organelles as they
move to each stage of RBC development
Reticulocyte
 a young erythrocyte w/c exits the bone
marrow & enters the circulation to begin
its role of O2 transport
 becomes a mature erythrocyte within 1
to 2 days after its release from the bone
marrow
Erythrocyte
 formed when the reticulocyte’s
cytoplasm is totally occupied by HGB
molecules & loses its remaining cellular
organelles
 the mature RBC
Erythropoietin
 the hemopoietic growth factor released
by the kidneys w/c stimulates the
maturation of proerythroblasts into
reticulocytes
 renal failure can thus cause anemia
a) Duration of erythropoiesis: 5-9 days
b) A young erythrocyte w/c exits the bone
marrow & enters the circulation to begin its
role of o2 transport
c) Becomes a mature erythrocyte within 1 to 2
days after its release from the bone marrow
Folic acid & vitamin B12 :
 Are nutrients derived from the diet w/c
are required for DNA synthesis & thus,
for erythropoiesis
 Deficiency of these nutrients results in
anemia
Intrinsic factor :
 A chemical produced by the cells of the
stomach lining
 Binds with vit. B12 in food to promote
vit. B12 absorption in the small intestine
Pernicious anemia :
 A type of anemia w/c results either from
lack of vit. B12 in the diet or from
intrinsic factor deficiency.
Formation of Hemoglobin
During erythropoiesis, HGB is formed
when RBCs are still immature.
HGB synthesis is still possible in
immature RBCs since they still possess
nuclei, mitochondria & rough ER
As HGB molecules occupy the cytoplasm
of the RBCs, cellular organelles are
slowly ejected out of the immature RBC.
The RBC continues to synthesize HGB
until all the cellular organelles are lost
(until the reticulocyte stage of RBC
development)
HGB is formed from the combination of heme
& globin
Amino Acids :
are needed to synthesize globin
Iron:
a mineral needed to synthesize heme
sources of iron for HGB synthesis:
stored iron in the human liver
decomposed HGB from worn-out &
destroyed RBCs
diet (iron-rich foods include organ meats,
egg yolk & legumes)
transferrin:
a plasma protein, specifically an iron-
binding beta globulin, w/c facilitates the
transport of iron to the bone marrow for
HGB synthesis or to the liver for storage
ferritin:
 iron-storage protein found primarily in
the liver; stores iron for future use; when
the quantity of iron falls in the plasma,
iron is removed from ferritin & is once
again transported by transferrin
The RBC Life Cycle
Since mature RBCs do not have nuclei,
they could not divide nor repair
themselves
Plasma membrane of RBCs eventually
become fragile with age & are likely
burst due to wear & tear
ave. lifespan of RBCs: 120 days
Spleen =
the graveyard of RBCs; the site where
worn-out RBCs are destroyed &
sequestered/removed from the
circulation
after removal from the circulation,
worn-out RBCs are broken down & their
breakdown products are recycled &
used in numerous metabolic processes,
including the formation of new RBCs
Regulation of RBC Production
Usually, the rate of RBC production equals the
rate of RBC destruction.
To maintain normal numbers of RBCs, new
mature cells must enter the bloodstream at a
rate of at least 2 million per second.
However, if hypoxia occurs, then RBC
production is stimulated at a rate faster than its
destruction.
Hypoxia
 refers to below normal O2 levels in the
body w/c can be due to:
 high altitude (the higher land is from sea
level, the lower the O2 in the air)
 high  O2 demand (e.g. physiologic
stress)
 Low O2 supply (e.g. chronic respiratory
disease)
stimulates the kidneys to  its secretion of
erythropoietin
 erythropoietin  RBC production &
HGB synthesis  O2 levels in the body
Testosterone
the hormone in males w/c stimulate the
release of erythropoietin
the reason why males have higher Hct
as well as RBC & HGB counts than
females aside from the females having
their regular menstruation
WHITE BLOOD CELLS (WBCs)
or leukocytes (“leuko” means white)
less numerous than RBCs
n° WBC count: 5,000 to 10,000 cells per
cubic millimeter (mm3 or μL) of blood
like the RBCs, they also arise from
hemocytoblasts in red bone marrow
depending on each type, they
differentiate from the myeloid or
lymphoid stem cells
however, their development is
stimulated by 2 diff. hemopoietic growth
factors: (a) interleukins& (b) colony-
stimulating factors
functions of mature WBCs:
protects the body by engulfing invading
microbes, releasing chemicals that
initiate immune responses, or
producing antibodies
removes dead cells & debris from the
tissues by phagocytosis
leukocytosis :
medical term for high overall WBC
count (>10,000/μL)
a normal, protective response to
stresses such as invading microbes,
strenuous exercise, anesthesia, &
surgery
leukopenia :
medical term for an abnormally low
WBC count (<5,000/ μL)
is never beneficial & indicates that one
is immunocompromised (at risk for
infection)
causes include radiation &
chemotherapy
characteristics of mature WBCs:
the only formed element of blood that
is a “complete” cell (is nucleated & has
several organelles)
do not contain hemoglobin
characteristics of mature WBCs:
are capable of self-locomotion
diapedesis =
the process in w/c WBCs (unlike RBCs)
can leave the capillaries by squeezing
bet. epithelial cells of capillary walls &
migrate or travel from the blood to the
interstitial fluid of invaded tissue
chemotaxis =
the ability of WBCs to migrate to
invaded tissues in response to
chemicals released by the attacked
tissues & toxins produced by microbes
 human leukocyte antigens (HLA):
 are membrane proteins in the WBCs w/c
are representative of the antigens
present on all cells of an individual
are cell-identity markers w/c recognize
“self” from “non-self”
Classification of WBCs
1. Granulocytes
o are WBCs with visible cytoplasmic
granules when stained
 Neutrophils (NEU)
o also called polymorphonuclear
o n° neutrophil count: 55% to 70% of
one’s total WBC
o their levels usually increase during
acute bacterial infections
attracted by bacterial products, they
are the first to arrive at the site of
invasion since they migrate quickly
functions:
o being phagocytes, they engulf
microorganisms especially bacteria
secrete chemicals that promote
inflammation
o release bacteria-destroying
substances (e.g. lysozymes) into the
surrounding of the infected tissue
segmenters =
 or “segs”; specific name for the mature
neutrophils; first to increase when there
is an infection but they have shorter life
spans & die quickly in an infection
bands =
 specific name for the immature
neutrophils; their levels increase when
segmenters die rapidly esp. during a
severe infection; since they are
immature, they are less efficient
phagocytes
pus =
 an accumulation of cell debris, & fluid at
sites of infection; a normal response
especially to bacterial infections but
sometimes, if in excess, need to be
evacuated for antibiotic treatment to
penetrate infected tissues
 Leukocytes (pmns)
o the most abundant WBC
 Basophils (BAS)
o the least abundant & rarest of the
WBCs
o n° basophil count: 0.5% to 1% of
one’s total WBC
o their cytoplasmic granules contain a
variety of substances
their levels increase during allergic
reactions & parasitic infections
o substances secreted:
histamine =
 mediates inflammation; makes
capillaries more permeable,
allowing tissue fluid in the
damaged area & makes tissue
swollen (as in an allergy)
heparin =
o an anticoagulant that helps
prevent abnormal clotting w/in
blood vessels
 Eosinophils (EOS)
o n° eosinophil count: 1% to 3% of
one’s total WBC
o their cytoplasmic granules contain a
variety of digestive enzymes that
function during allergic reactions &
parasitic infections.
o functions:
o release chemicals that kill
parasitic worms
2. Agranulocytes
 are WBCs with no visible cytoplasmic
granules when stained
 Lymphocytes (LYM)
o smallest of the WBCs
the 2nd most abundant WBC
n° lymphocyte count: 20% to
40% of one’s total WBC
o mostly reside in lymphatic
tissue (hence, their name)
o are effective in fighting
infectious organisms because
each lymphocyte recognizes &
acts against an antigen
o usually increase during acute
viral infections
antigen =
 any specific “non-self” or foreign
molecule that induces a response
from a lymphocyte
 has 3 types:
T cells =
help recognize antigens &
may directly destroy some
antigens
B cells =
become plasma cells that
produce antibodies w/c
bind to antigens
natural killer (NK) cells =
destroy foreign cells by
chemically rupturing their
membranes
o functions:
o regulate immunity
o contribute to allergic reaction
o reject grafts or donated
organs
o control tumors
 Monocytes (MON)
o largest of the WBCs
n° monocyte count: 3% to 8% of
one’s total WBC
o when they leave the bloodstream,
they enlarge & differentiate into
macrophages
o their numbers usually increase
during a chronic infection
macrophages =
 like the neutrophils, they
phagocytize bacteria, dead cells
& any other debris w/in the
tissues; although they take
longer to reach a site of
infection than neutrophils, they
are more efficient phagocytes
fixed macrophages =
 type of macrophage which
reside in a particular tissue;
examples include alveolar
macrophages in the lungs &
macrophages in the spleen
wandering macrophages =
 type of macrophage which roam
the tissues & gather at sites of
infection or inflammation
PLATELETS (PLTs)
o or thrombocytes
o n° PLT count: 140,000 to 440,000 cells
per cubic millimeter (mm3 or μL) of
blood
o are not true cells but are cellular
fragments that are remnants of bone
marrow cells called megakaryocytes
megakaryocytes =
 immature cells that give rise to
PLTs; differentiate from
hemocytoblasts in red bone
marrow

thrombopoietin =
 a hormone/hemopoietic
growth factor produced by
the liver that increases the
rate of PLT production by
stimulating the
differentiation of myeloid
stem cells to
megakaryocytes
characteristics of PLTs:
 shape: irregularly disc-shaped
 no nucleus
 have a short life span (5-9 days)
 its main function is for blood clotting
thrombocytopenia =
 the medical term for an
abnormally low PLT count
w/c indicates an risk for
bleeding
HEMOSTASIS
 not to be confused w/ “homeostasis”
 stimulated in response to rupture or damage to
blood vessels
Hemorrhage
 refers to the loss of a large amount of blood
from the blood vessels
 can be prevented if hemostasis is successful
 if too extensive, it needs medical intervention
Mechanisms of Hemostasis
1. Vascular spasm
 blood vessel damaged in traumatized
tissue  PLTs in the area of the rupture
release serotonin  smooth muscle in
blood vessel wall contracts
vasoconstriction & spasm  low
blood flow to ruptured vessel
 this process occurs immediately once
blood vessel is damaged
2. Platelet Plug Formation
 this process occurs within seconds from
damage to the blood vessel
 first, PLTs contact & stick to parts of the
damaged blood vessel (this process is
called, platelet adhesion)
 second, PLTs are activated & release
thromboxane A2 & ADP (this process is
called, platelet release reaction)
Thromboxane A2 & ADP activate nearby
PLTs.

 o most of them are manufactured in the liver
o many of them require vitamin K for their
synthesis (factors X, IX, VII & II)
o vitamin K = produced by the bacteria inhabiting
the large intestine & stored in the liver
o they are designated by Roman numerals & are
numbered in the order of their discovery

Number Names
 I Fibrinogen
 third, the release of ADP & thromboxane A2
II Prothrombin
makes other PLTs in the area sticky, & the
III Tissue thromboplastin
stickiness of these PLTs causes them to adhere IV Calcium ions
to the originally activated PLTs (this gathering V Labile factor
of PLTs is called, platelet aggregation) VII Stable factor
o
Number Names
VIII Antihemophilic factor
IX Christmas factor
X Stuart-Prower factor
XI Plasma thromboplastin antecedent
XII Hageman factor
o XIII Fibrin stabilizing factor

 platelet aggregation then promotes the

Sum m ary of
formation of a platelet plug Clotting
 this process, however, is usually only effective Cascade
for damage to small blood vessels

3. Blood clotting
 also called blood coagulation
 is a series of chemical reactions that
culminates in formation of fibrin threads
involves several substances known as
clotting factors
 is thus a complex cascade of enzymatic
reactions in which each clotting factor o
activates many molecules of the next one in
a fixed sequence Fibrin Form ation
 the clot begins to develop within 15-20
seconds if the trauma is severe & about 1-2
minutes if the trauma is minor

clot =
a network of insoluble protein fibers called
fibrin in w/c the formed elements of blood
are trapped

Clotting Factors
o include Ca++ ions, certain plasma proteins,
inactive enzymes and chemicals released by
PLTs & damaged tissues
o
Hemostatic Control Mechanisms
o are “brakes” which prevent abnormal blood
clotting
1. Fibrinolytic System
fibrinolysis =
 dissolution of a clot
this system prevents abnormal clotting
by dissolving small, inappropriate clots
its also dissolves clots at a site of
damage once the damage is repaired
plasminogen =
 an inactive plasma enzyme
incorporated into the clot when a clot is
formed
plasmin =
 or fibrinolysin; the active enzyme that
dissolves clots by digesting fibrin
threads & inactivating fibrinogen &
thrombin
tissue plasminogen activator (t-PA) =
 substance released by injured tissues
that activate plasminogen to plasmin
2. Surface of endothelium
o the smoothness of the endothelium
prevents the activation of the intrinsic
coagulation pathway
o when this smoothness is lost, it activates
factor XII & the PLTs
endothelium =
the simple squamous epithelium w/c forms the
inner lining of blood vessels
3. Natural anticoagulants
anticoagulant =
o a substance w/c delays, suppresses or
prevents blood clotting usually by
disrupting a chemical reaction in the
clotting cascade
antithrombin =
o a natural anticoagulant produced by the
liver w/c blocks the action of several
clotting factors including factor XII, X &
II
heparin =
o a natural anticoagulant produced by the
basophils; combines w/ antithrombin &
increases its effectiveness in blocking
thrombin
ABO Blood Group
 is based on the presence (or absence) of two
major protein antigens on RBC membranes -
antigen A & antigen B.
 Blood types & their antigens:
Type A = RBCs display only antigen A
Type B = display only antigen B
Type AB = both A & B antigens
Type O = have neither antigen A nor B on RBCs
 whenever antigen A is absent in RBCs, an
antibody called anti-A is produced, and
whenever antigen B is absent, an antibody
called anti-B is produced.
 thus, an antibody & its corresponding antigen
are not normally present in the same blood
specimen.
Blood type Antigen Antibody
A A Anti-B
B B Anti-A
AB A and B Neither anti-A nor anti-B
O Neither A nor B Both anti-A and anti-B
 when the antibody (e.g. anti-A) & its
corresponding antigen (e.g. antigen A) are
combined, agglutination results such as in
blood type mismatch during a blood transfusion
ABO blood typing
 the screening of one’s blood for the presence of
antibodies to determine ABO blood type
 single drops of blood are mixed with different
antisera, which are solutions that contain
antibodies
 One drop of blood is mixed with anti-A serum,
w/c contains anti-A antibodies that will
agglutinate RBCs that possess A antigens. Hem olytic Disease of the N ew born
 Another drop is mixed with anti-B serum, w/c
contains anti-B antibodies that will agglutinate
RBCs that possess B antigens.
 If the RBCs agglutinate only when mixed with
anti-A serum, the blood is type A. If the RBCs
agglutinate only when mixed with anti-B serum,
the blood is type B. The blood is type AB if both
drops agglutinate; if neither drop agglutinates,
the blood is type O.
Blood type
Characteristic
A B AB O
Compatible A, O B, O A, B, AB, O O
donor blood
types
(no hemolysis)
Incompatible B, AB A, AB none A, B, AB
donor blood
types
(hemolysis)

 Type “O”
known as the universal donor
they usually can give blood to the other
ABO blood types w/o causing an ABO
transfusion reaction.
 the donor’s RBCs have no ABO surface
antigens &, therefore, do not react w/ the
recipient’s anti-A or anti-B antibodies.

 Type “AB”
known as the universal recipient
the recipient’s plasma has no anti-A nor
anti-B antibodies & therefore, do not react
w/ the any ABO surface antigen on donor’s
RBCs

 so named because it was first studied in the

rhesus monkey
 also called "D antigen”

Human erythrocytes are classified as Rh positive or

Rh negative depending solely on the presence or
absence of the D antigen

Designated as either Rh(+) or Rh (-); if combined

with one’s ABO blood type, could be written as O+
or O- depending on Rh blood type

Rh incompatibility is responsible for the hemolytic

disease of the newborn (HDN) or erythroblastosis
fetalis which occurs in an Rh(-) mother which leads
to death of second born Rh(+) child