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Chapter 19

The Cardiovascular System: The


Blood

Lecture Outline
1
Chapter 19 The
Cardiovascular System:
The Blood

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Physiology, 11e
Fluids of the Body
• Cells of the body are serviced by 2
fluids
– blood
• composed of plasma and a variety of cells
• transports nutrients and wastes
– interstitial fluid
• bathes the cells of the body
• Nutrients and oxygen diffuse from
the blood into the interstitial fluid &
then into the cells
• Wastes move in the reverse direction
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Functions of Blood
• Transportation
– O2, CO2, metabolic wastes, nutrients, heat
& hormones
• Regulation
– helps regulate pH through buffers
– helps regulate body temperature
• vasodilatation of surface vessels dump heat
– helps regulate water content of cells by
interactions with dissolved ions and
proteins
• Protection from disease & loss of blood
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Physical Characteristics of
Blood
• Thicker (more viscous) than water and
flows more slowly than water
• Temperature of 100.4 degrees F
• pH 7.4 (7.35-7.45)
• 8 % of total body weight
• Blood volume
– 5 to 6 liters in average male
– 4 to 5 liters in average female
– hormonal negative feedback systems
maintain constant blood
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Techniques of Blood Sampling
• Venipuncture
– sample taken from vein with
hypodermic needle & syringe
– median cubital vein: Anterior to the
elbow. Common site for venipuncture
(see page 717)
– why not stick an artery?
• less pressure in veins
• closer to the surface thus easier to
sample
• Finger or heel stick
– common technique for diabetics to
monitor daily blood
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COMPONENTS OF BLOOD
• Blood consists of 55% plasma and
45% formed elements (Figure 19.1).
• Blood plasma consists of 91.5% water
and 8.5% solutes.
• Principal solutes include proteins
(albumins, globulins, fibrinogen),
nutrients, enzymes, hormones,
respiratory gases, electrolytes, and
waste products.
• Table 19.1 summarizes the
chemical composition of
plasma. Principles of Human Anatomy and
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Components of Blood
Hematocrit: Is the
percentage of total blood
volume occupied by RBCs
– 55% plasma
– 45% cells
• 99% RBCs
• < 1% WBCs and platelets

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Blood Plasma
• 0ver 90% water
• 7% plasma proteins
• created in liver
• confined to bloodstream
– albumin
• maintain blood osmotic pressure
– globulins (immunoglobulins)
• antibodies bind to foreign
substances called antigens
• form antigen-antibody complexes
– fibrinogen
• for clotting
• 2% other substances
– electrolytes, nutrients, hormones, gases, waste products

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Formed Elements of Blood
• Red blood cells ( erythrocytes )
• White blood cells ( leukocytes )
– granular leukocytes
• neutrophils, eosinophils, basophils
– agranular leukocytes
• lymphocytes = T cells, B cells, and natural killer
cells
• monocytes
• Platelets (special cell fragments)

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FORMATION OF BLOOD
CELLS
• Blood cells are formed from
pluripotent hematopoietic stem
cells (Figure 19.3).
• Originating from the pluripotent stem
cells are the myeloid stem cells
and lymphoid stem cells.

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Hematocrit
• Percentage of blood occupied by RBCs
– female normal range
• 38 - 46% (average of 42%)
– male normal range
• 40 - 54% (average of 46%)
• Testosterone higher in males stimulates production of
Erythropoietin (EPO) in kidneys which stimulates RBC
production
• Anemia
– not enough RBCs or not enough hemoglobin
• Polycythemia
– too many RBCs (over 65%)
– dehydration, tissue hypoxia, blood doping in athletes

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Formation of Blood Cells
• Most blood cells types need to be continually
replaced
– die within hours, days or weeks
– process of blood cells formation is hematopoiesis or
hemopoiesis
• In the embryo
– occurs in yolk sac, liver, spleen, thymus, lymph
nodes & red bone marrow
• In adult
– occurs only in red marrow of flat bones like sternum,
ribs, skull & pelvis and ends of long bones

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Hematopoiesis

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Hemopoietic Growth Factors
• Regulate differentiation & proliferation
• Erythropoietin (EPO)
– produced by the kidneys increase RBC
precursors
• Thrombopoietin (TPO)
– hormone from liver stimulates platelet
formation
• Cytokines are local hormones of
bone marrow
– produced by some marrow cells to
stimulate proliferation in other marrow15
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Blood Cells
• Myeloid stem cells give rise to RBCs,
platelets, and all WBCs except for
lymphocytes.
• Lymphoid stem cells give rise to
lymphocytes.
• Myeloid stem cells differentiate into
progenitor cells or precursor cells
(blast cells) which will develop into
the actual formed elements of blood.
• Lymphoid stem cells differentiate into
pre-B and prothymocytes which
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develop into B-lymphocytes and T-
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Red Blood Cells or Erythrocytes

(Figure 19.4a)
Contain oxygen-carrying protein hemoglobin that gives
blood its red color
– 1/3 of cell’s weight is hemoglobin
• Biconcave disk 8 microns in diameter
– increased surface area/volume ratio
– flexible shape for narrow passages
– no nucleus or other organelles
• no cell division or mitochondrial ATP formation
• Normal RBC count
– male 5.4 million/drop (cubic mm) ---- female 4.8
million/drop
– new RBCs enter circulation at 2 million/second

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Hemoglobin

• Globin protein consisting of 4 polypeptide chains


• One heme pigment attached to each polypeptide chain
– each heme contains an iron ion (Fe+2) that can combine
reversibly with one oxygen molecule
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Transport of O2, CO2 and Nitric Oxide
• Each hemoglobin molecule can carry 4
oxygen molecules from lungs to
tissue cells
• Hemoglobin transports 23% of total
CO2 waste from tissue cells to lungs
for release
– combines with amino acids in globin
portion of Hb
• Hemoglobin transports nitric oxide &
super nitric oxide helping to
regulate BP
– iron ions pickPrinciples
up nitric oxide (NO) & super
of Human Anatomy and
nitric oxide (SNO)& transport
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RBCs
• Production of abnormal hemoglobin
can result in serious blood disorders
such as thalassemia and sickle
cell anemia. (Figure 19.15)

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RBC Life Cycle

• RBCs live only 120 days


– wear out from bending to fit through capillaries
– no repair possible due to lack of organelles
• Worn out cells removed by fixed macrophages in
spleen & liver
• Breakdown products are recycled

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Fate of Components of
Heme
• Iron(Fe+3)
– transported in blood attached to transferrin
protein
– stored in liver, muscle or spleen
• attached to ferritin or hemosiderin protein
– in bone marrow being used for hemoglobin
synthesis
• Biliverdin (green) converted to
bilirubin (yellow)
– bilirubin secreted by liver into bile
• converted to urobilinogen then stercobilin
(brown pigment in feces) by bacteria of large
intestine Principles of Human Anatomy and
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• if reabsorbed from intestines into blood is
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Erythropoiesis: Production
• of RBCs
Erythrocyte formation, called erythropoiesis,
occurs in adult red bone marrow of certain
bones (Figure 19.3).
• The main stimulus for erythropoiesis is hypoxia
(Figure 19.6).

• Proerythroblast starts to produce


hemoglobin
• Many steps later, nucleus is ejected & a
reticulocyte is formed
– orange in color with traces of visible rough ER
• Reticulocytes escape from bone marrow into
the blood
• In 1-2 days, they eject the remaining
organelles to become a mature
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RBC 23
Feedback Control of RBC
Production
• Tissue hypoxia (cells not
getting enough O2)
– high altitude since air has
less O2
– anemia
• RBC production falls below
RBC destruction
– circulatory problems
• Kidney response to
hypoxia
– release erythropoietin
– speeds up development of
proerythroblasts into
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WHITE BLOOD CELLS
• Leukocytes (white blood cells or
WBCs) are nucleated cells and do not
contain hemoglobin.
• Leukocytes have surface proteins, as
do erythrocytes. They are called
major histocompatibility antigens
(MHC), are unique for each person
(except for identical siblings), and
can be used to identify a tissue.
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WBC Physiology
• Less numerous than RBCs
– 5000 to 10,000 cells per drop of blood
– 1 WBC for every 700 RBC
• Leukocytosis is a high white blood cell
count
– microbes, strenuous exercise, anesthesia or
surgery
• Leukopenia is low white blood cell
count
– radiation, shock or chemotherapy
• Only 2% of total WBC population is in
circulating blood at any given time
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Function
• Different WBCs combat of inflammation
WBCs and
infection in different ways.
– Neutrophils and wandering or fixed
macrophages (which develop from
monocytes) do so through phagocytosis.
– Eosinophils combat the effects of histamine in
allergic reactions, phagocytize antigen-
antibody complexes, and combat parasitic
worms.
– Basophils develop into mast cells that liberate
heparin, histamine, and serotonin in allergic
reactions that intensify the inflammatory
response.
– B lymphocytes, in response to the presence of
foreign substances called antigens,
differentiate into tissue plasma cells that
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Function of WBCs
• WBCs leave the blood stream by
emigration (Figure 19.8).
• Some WBCs, particularly neutrophils
and macrophages, are active in
phagocytosis.
• The chemical attraction of WBCs to a
disease or injury site is termed
chemotaxis.

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WBC examination
• A differential white blood cell count
is a diagnostic test in which specific
white blood cells are enumerated.
Because each type of WBC plays a
different role, determining the
percentage of each type in the blood
assists in diagnosing the condition.
• Table 19.2 shows the significance of
elevated or depressed counts of the
various WBCs.
• Bone marrow transplants may be used
to treat several types of anemia,
leukemia, and numerous other blood
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Complete Blood Count
• Screens for anemia and
infection
• Total RBC, WBC & platelet counts;
differential WBC; hematocrit and
hemoglobin measurements
• Normal hemoglobin range
– infants have 14 to 20 g/100mL of
blood
– adult females have 12 to 16 g/100mL
of blood
– adult males have 13.5 to 18g/100mL
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Differential WBC Count
• Detection of changes in numbers of
circulating WBCs (percentages of each
type)
– indicates infection, poisoning, leukemia,
chemotherapy, parasites or allergy reaction
• Normal WBC counts
– neutrophils 60-70% (up if bacterial
infection)
– lymphocyte 20-25% (up if viral infection)
– monocytes 3 -- 8 % (up if fungal/viral
infection) Principles of Human Anatomy and
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PLATELETS
• Thrombopoietin stimulates myeloid stem cells to produce
platelets.
• Myeloid stem cells develop into megakaryocyte-colony-
forming cells that develop into megakaryoblasts (Figure
19.2).
• Megakaryoblasts transform into megakaryocytes which
fragment.
• Each fragment, enclosed by a piece of cell membrane, is a
platelet (thrombocyte).
• Normal blood contains 250,000 to 400,000
platelets/mm3. Platelets have a life span of only 5 to 9
days; aged and dead platelets are removed by fixed
macrophages in the spleen and liver.

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HEMOSTASIS
• A clot is a gel consisting of a network of
insoluble protein fibers (fibrin) in which
formed elements of blood are trapped (Figure
19.10).
• The chemicals involved in clotting are known as
coagulation (clotting) factors; most are in blood
plasma, some are released by platelets, and
one is released from damaged tissue cells
(SeeTable 19.4).
• Blood clotting involves a cascade of reactions
that may be divided into three stages:
formation of prothrombinase (prothrombin
activator), conversion of prothrombin into
thrombin, and conversion of soluble
fibrinogen intoPrinciples
insoluble fibrin (Figure
of Human Anatomy and
19.11). Physiology, 11e
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Hemostasis
Extrinsic pathway:
• Initiated by cells outside of
blood vessels such as cells of
damaged tissue.
• Fewer steps are involved and
occurs rapidly within a matter of
seconds.
• Extrinsic cells release a protein
called the Tissue Factor (TF) aka
Thromboplastin into the blood.
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Hemostasis
Intrinsic Pathway:
• More complex than extrinsic and
occurs more slowly, usually
several minutes.
• The activators are either in
direct contact with blood or
present inside blood.

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HEMOSTASIS
• The clotting cascade can be initiated
by either the extrinsic pathway or
the intrinsic pathway.
• Normal coagulation requires vitamin
K and also involves clot retraction
(tightening of the clot) and
fibrinolysis (dissolution of the clot).

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Hemostasis
• Stoppage of bleeding in a quick &
localized fashion when blood vessels
are damaged
• Prevents hemorrhage (loss of a large
amount of blood)
• Methods utilized
– vascular spasm
– platelet plug formation
– blood clotting (coagulation = formation of
fibrin threads)
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Blood Clotting
• Blood drawn from the body thickens into a
gel
– gel separates into liquid (serum) and a
clot of insoluble fibers (fibrin) in which the
cells are trapped
• If clotting occurs in an unbroken vessel
is called a thrombosis
• Substances required for clotting are
Ca+2, enzymes synthesized by liver
cells and substances released by
platelets or damaged tissues

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Intravascular Clotting
• Thrombosis
– clot (thrombus) forming in an unbroken
blood vessel
• forms on rough inner lining of BV
• if blood flows too slowly (stasis) allowing clotting
factors to build up locally & cause coagulation
– may dissolve spontaneously or dislodge &
travel
• Embolus
– clot, air bubble or fat from broken bone in
the blood
• pulmonary embolus is found in lungs
• Low dose aspirin blocks synthesis of
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Anticoagulants and Thrombolytic Agents

• Anticoagulants suppress or prevent


blood clotting
– heparin
• administered during hemodialysis and surgery
– warfarin (Coumadin)
• antagonist to vitamin K so blocks synthesis of
clotting factors
• slower than heparin
– stored blood in blood banks treated
with citrate phosphate dextrose (CPD)
that removes Ca+2
• Thrombolytic agents are injected to
dissolve clots Principles of Human Anatomy and
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ABO Group
• In the ABO system, agglutinogens
(antigens) A and B determine
blood types (Figure 19.12).
• Plasma contains agglutinins
(antibodies), designated as a and b,
that react with agglutinogens that
are foreign to the individual.
• Table 19.5 indicates the
incidence of ABO and Rh
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Blood Groups and Blood
Types

• RBC surfaces are marked by genetically


determined glycoproteins & glycolipids
– agglutinogens or isoantigens
– distinguishes at least 24 different
blood groupsPrinciples of Human Anatomy and
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RH blood groups
• Antigen was discovered in blood of
Rhesus monkey
• People with Rh agglutinogens on
RBC surface are Rh+. Normal
plasma contains no anti-Rh
antibodies
• Antibodies develop only in Rh- blood
type & only with exposure to the
antigen
– transfusion of positive blood
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Hemolytic Disease of
Newborn

• Rh negative mom and Rh+ fetus will have mixing of blood at birth
• Mom's body creates Rh antibodies unless she receives a RhoGam shot
soon after first delivery, miscarriage or abortion
– RhoGam binds to loose fetal blood and removes it from body
before she reacts
• In 2nd child, hemolytic disease of the newborn may develop causing
hemolysis of the fetal RBCs
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Universal Donors and
Recipients
• People with type AB blood
called “universal recipients”
since have no antibodies in
plasma
– only true if cross match the blood
for other antigens
• People with type O blood
cell called “universal
donors” since have no antigens
on their cells
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DISORDERS: HOMEOSTATIC
IMBALANCES
• Anemia
• Sickle-cell
• Hemophilia
• Disseminated
intravascular clotting
• Acute leukemia
• chronic leukemia

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