Chapter 19
The Cardiovascular System: The Blood
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
Hematology is study of blood and blood disorders
Functions of Blood
Transportation
O2, CO2, metabolic
wastes, nutrients, heat & hormones
Regulation
helps regulate pH through buffers
helps regulate body temperature
coolant properties of water
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
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
volume and osmotic pressure
Techniques of Blood Sampling
Venipuncture
sample taken from vein with hypodermic needle & syringe
median cubital vein (see page 717)
why not stick an artery?
less pressure
closer to the surface
Finger or heel stick
common technique for diabetics to monitor daily blood sugar
method used for infants
Components of Blood
Hematocrit
55% plasma
45% cells
99% RBCs
< 1% WBCs and platelets
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
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)
Hematocrit
Percentage of blood occupied by cells
female normal range
38 - 46% (average of 42%)
male normal range
40 - 54% (average of 46%)
testosterone
Anemia
not enough RBCs or not enough hemoglobin
Polycythemia
too many RBCs (over 65%)
dehydration, tissue hypoxia, blood doping in athletes
Blood Doping
Injecting previously stored RBC’s before an athletic event
more cells available to deliver oxygen to tissues
Dangerous
increases blood viscosity
forces heart to work harder
Banned by Olympic committee
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
Hematopoiesis
Medical Uses of Growth Factors
Available through recombinant DNA technology
recombinant erythropoietin (EPO) very effective in treating
decreased RBC production of end-stage kidney disease
other products given to stimulate WBC formation in cancer
patients receiving chemotherapy which kills bone marrow
granulocyte-macrophage colony-stimulating factor
granulocyte colony stimulating factor
thrombopoietin helps prevent platelet depletion during
chemotherapy
Red Blood Cells or Erythrocytes
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 ---- female 4.8 million/drop
new RBCs enter circulation at 2 million/second
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
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
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 reticulocytes
WBC Anatomy and Types
All WBCs (leukocytes) have a nucleus and no hemoglobin
Granular or agranular classification based on presence
of cytoplasmic granules made visible by
staining
granulocytes are neutrophils, eosinophils or basophils
agranulocytes are monocyes or lymphocytes
Neutrophils (Granulocyte)
Polymorphonuclear Leukocytes or Polys
Nuclei = 2 to 5 lobes connected by thin strands
older cells have more lobes
young cells called band cells because of horseshoe shaped
nucleus (band)
Fine, pale lilac practically invisible granules
Diameter is 10-12 microns
60 to 70% of circulating WBCs
Eosinophils (Granulocyte)
Nucleus with 2 or 3 lobes connected by a thin strand
Large, uniform-sized granules stain orange-red with acidic
dyes
do not obscure the nucleus
Diameter is 10 to 12 microns
2 to 4% of circulating WBCs
Basophils (Granulocyte)
Large, dark purple, variable-sized granules stain with basic
dyes
obscure the nucleus
Irregular, s-shaped, bilobed nuclei
Diameter is 8 to 10 microns
Less than 1% of circulating WBCs
Lymphocyte (Agranulocyte)
Dark, oval to round nucleus
Cytoplasm sky blue in color
amount varies from
rim of blue to normal amount
Small cells 6 - 9 microns in diameter
Large cells 10 - 14 microns in diameter
increase in number during viral infections
20 to 25% of circulating WBCs
Monocyte (Agranulocyte)
Nucleus is kidney or horse-shoe shaped
Largest WBC in circulating blood
does not remain in blood long before migrating to the
tissues
differentiate into macrophages
fixed group found in specific tissues
alveolar macrophages in lungs
kupffer cells in liver
wandering group gathers at sites of infection
Diameter is 12 - 20 microns
Cytoplasm is a foamy blue-gray
3 to 8% o circulating WBCs
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
rest is in lymphatic fluid, skin, lungs, lymph nodes &
spleen
Emigration & Phagocytosis in WBCs
WBCs roll along endothelium, stick to it & squeeze
between cells.
adhesion molecules (selectins) help WBCs stick to
endothelium
displayed near site of injury
molecules (integrins) found on neutrophils assist in
movement through wall
Neutrophils & macrophages phagocytize bacteria &
debris
chemotaxis of both
kinins from injury
site & toxins
Neutrophil Function
Fastest response of all WBC to bacteria
Direct actions against bacteria
release lysozymes which destroy/digest bacteria
release defensin proteins that act like antibiotics &
poke holes in bacterial cell walls destroying them
release strong oxidants (bleach-like, strong chemicals )
that destroy bacteria
Monocyte Function
Take longer to get to site of infection, but arrive in
larger numbers
Become wandering macrophages, once they leave the
capillaries
Destroy microbes and clean up dead tissue following an
infection
Basophil Function
Involved in inflammatory and allergy reactions
Leave capillaries & enter connective tissue as mast
cells
Release heparin, histamine & serotonin
heighten the inflammatory response and account for
hypersensitivity (allergic) reaction
Eosinophil Function
Leave capillaries to enter tissue fluid
Release histaminase
slows down inflammation caused by basophils
Attack parasitic
worms
Phagocytize antibody-antigen complexes
Lymphocyte Functions
B cells
destroy bacteria and their toxins
turn into plasma cells that produces antibodies
T cells
attack viruses, fungi, transplanted organs, cancer cells
& some bacteria
Natural killer cells
attack many different microbes & some tumor cells
destroy foreign invaders by direct attack
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)
eosinophil 2 -- 4 %
(up if parasite or allergy reaction)
basophil <1% (up
if allergy reaction or hypothyroid)
Bone Marrow Transplant
Intravenous transfer of healthy bone marrow
Procedure
destroy sick bone marrow with radiation & chemotherapy
donor matches surface antigens on WBC
put sample of donor marrow into patient's vein for reseeding
of bone marrow
success depends on histocompatibility of donor &
recipient
Treatment for leukemia, sickle-cell, breast, ovarian or
testicular cancer, lymphoma or aplastic anemia
Platelet (Thrombocyte) Anatomy
Disc-shaped, 2 - 4 micron cell fragment with no nucleus
Normal platelet count is 150,000-400,000/drop of blood
Other blood cell counts
5 million red &
5-10,000 white blood cells
Platelets--Life History
Platelets form in bone marrow by following steps:
myeloid stem cells to megakaryocyte-colony forming cells to
megakaryoblast to megakaryocytes whose cell fragments form platelets
Short life span (5 to 9 days in bloodstream)
formed in bone marrow
few days in circulating blood
aged ones removed by fixed macrophages in liver and spleen
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 of blood
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)
Vascular Spasm
Damage to blood vessel produces stimulates pain receptors
Reflex contraction of smooth muscle of small blood vessels
Can reduce blood loss for several hours until other
mechanisms can take over
Only for small blood vessel or arteriole
Platelet Plug Formation
Platelets store a lot of chemicals in granules needed for
platelet plug formation
alpha granules
clotting factors
platelet-derived growth factor
cause proliferation of vascular endothelial cells, smooth
muscle & fibroblasts to repair damaged vessels
dense granules
ADP, ATP, Ca+2, serotonin, fibrin-stabilizing factor, &
enzymes that produce thromboxane A2
Steps in the process
(1) platelet adhesion
(2) platelet release reaction (3) platelet aggregation
Platelet Adhesion
Platelets stick to exposed collagen underlying damaged
endothelial cells in vessel wall
Platelet Release Reaction
Platelets activated by adhesion
Extend projections to make contact with each other
Release thromboxane A2 & ADP activating other platelets
Serotonin & thromboxane A2 are vasoconstrictors
decreasing blood flow through the injured vessel
Platelet Aggregation
Activated platelets stick together and activate new
platelets to form a mass called a platelet plug
Plug reinforced by fibrin threads formed during clotting
process
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
Clotting is a cascade of reactions in which each clotting
factor activates the next in a fixed sequence resulting in the formation of
fibrin threads
prothrombinase & Ca+2 convert prothrombin into thrombin
thrombin converts fibrinogen into fibrin threads
Overview of the Clotting Cascade
Prothrombinase is formed by either the intrinsic or
extrinsic pathway
Final common pathway produces fibrin threads
Extrinsic Pathway
Damaged tissues leak tissue factor (thromboplastin) into
bloodstream
Prothrombinase forms in seconds
In the presence of Ca+2, clotting factor X combines with V
to form prothrombinase
Intrinsic Pathway
Activation occurs
endothelium is damaged & platelets come in contact with
collagen of blood vessel wall
platelets damaged & release phospholipids
Requires several minutes for reaction to occur
Substances involved: Ca+2 and clotting factors XII, X and V
Final Common Pathway
Prothrombinase and Ca+2
catalyze the conversion of prothrombin to thrombin
Thrombin
in the presence of Ca+2 converts soluble fibrinogen to
insoluble fibrin threads
activates fibrin stabilizing factor XIII
positive feedback effects of thrombin
accelerates formation of prothrombinase
activates platelets to release phospholipids
Clot Retraction & Blood Vessel Repair
Clot plugs ruptured area of blood vessel
Platelets pull on fibrin threads causing clot retraction
trapped platelets release factor XIII stabilizing the fibrin
threads
Edges of damaged vessel are pulled together
Fibroblasts & endothelial cells repair the blood vessel
Role of Vitamin K in Clotting
Normal clotting requires adequate vitamin K
fat soluble vitamin absorbed if lipids are present
absorption slowed if bile release is insufficient
Required for synthesis of 4 clotting factors by hepatocytes
factors II (prothrombin), VII, IX and X
Produced by bacteria in large intestine
Hemostatic Control Mechanisms
Fibrinolytic system dissolves small, inappropriate clots
& clots at a site of a completed repair
fibrinolysis is dissolution of a clot
Inactive plasminogen is incorporated into the clot
activation occurs because of factor XII and thrombin
plasminogen becomes plasmin (fibrinolysin) which digests
fibrin threads
Clot formation remains localized
fibrin absorbs thrombin
blood disperses clotting factors
endothelial cells & WBC produce prostacyclin that
opposes thromboxane A2 (platelet adhesion & release)
Anticoagulants present in blood & produced by mast cells
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 thromboxane A2 &
reduces inappropriate clot formation
strokes, TIAs and myocardial infarctions
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
directly or indirectly activate plasminogen
streptokinase or
tissue plasminogen activator (t-PA)
Blood Groups and Blood Types
RBC surfaces are marked by genetically determined
glycoproteins & glycolipids
agglutinogens or isoantigens
distinguishes at least 24 different blood groups
ABO, Rh, Lewis, Kell, Kidd and Duffy systems
ABO Blood Groups
Based on 2 glycolipid isoantigens called A and B found on
the surface of RBCs
display only antigen A -- blood type A
display only antigen B -- blood type B
display both antigens A & B -- blood type AB
display neither antigen -- blood type O
Plasma contains isoantibodies or agglutinins to the A or B
antigens not found in your blood
anti-A antibody reacts with antigen A
anti-B antibody reacts with antigen B
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
during a pregnancy with a positive blood type fetus
Transfusion reaction upon 2nd exposure to the antigen
results in hemolysis of the RBCs in the donated blood
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
Transfusion and Transfusion Reactions
Transfer of whole blood, cells or plasma into the
bloodstream of recipient
used to treat anemia or severe blood loss
Incompatible blood
transfusions
antigen-antibody complexes form between plasma antibodies
& “foreign proteins” on donated RBC's (agglutination)
donated RBCs become leaky (complement proteins) & burst
loose hemoglobin causes kidney damage
Problems caused by incompatibility between donor’s cells and
recipient’s plasma
Donor plasma is too diluted to cause problems
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
theoretically can be given to anyone
Typing and Cross-Matching Blood
Mixing of incompatible blood causes agglutination (visible
clumping)
formation of antigen-antibody complex that sticks cells
together
not the same as blood clotting
Typing involves testing blood with known antisera that
contain antibodies A, B or Rh+
Cross-matching is to test by mixing donor cells with
recipient’s serum
Screening is to test recipient’s serum against known RBC’s
having known antigens
Anemia = Not Enough RBCs
Symptoms
oxygen-carrying capacity of blood is reduced
fatigue, cold intolerance & paleness
lack of O2 for ATP & heat production
Types of anemia
iron-deficiency =lack of absorption or loss of iron
pernicious = lack of intrinsic factor for B12 absorption
hemorrhagic = loss of RBCs due to bleeding (ulcer)
hemolytic = defects in cell membranes cause rupture
thalassemia = hereditary deficiency of hemoglobin
aplastic = destruction of bone marrow (radiation/toxins)
Sickle-cell Anemia (SCA)
Genetic defect in hemoglobin molecule (Hb-S) that changes 2
amino acids
at low very O2 levels, RBC is deformed by changes in
hemoglobin molecule within the RBC
sickle-shaped cells rupture easily = causing anemia &
clots
Found among populations in malaria belt
Mediterranean Europe, sub-Saharan Africa & Asia
Person with only one sickle cell gene
increased resistance to malaria because RBC membranes leak
K+ & lowered levels of K+ kill the parasite infecting the red blood cells
Hemophilia
Inherited deficiency of clotting factors
bleeding spontaneously or after minor trauma
subcutaneous & intramuscular hemorrhaging
nosebleeds, blood in urine, articular bleeding & pain
Hemophilia A lacks factor VIII (males only)
most common
Hemophilia B lacks factor IX (males only)
Hemophilia C (males & females)
less severe because alternate clotting activator exists
Treatment is transfusions of fresh plasma or concentrates of
the missing clotting factor
Disseminated Intravascular Clotting
Life threatening paradoxical presence of blood clotting and
bleeding at the same time throughout the whole body
so many clotting factors are removed by widespread clotting
that too few remain to permit normal clotting
Associated with infections, hypoxia, low blood flow rates,
trauma, hypotension & hemolysis
Clots cause ischemia and necrosis leading to multisystem
organ failure
Leukemia
Acute leukemia
uncontrolled production of immature leukocytes
crowding out of normal red bone marrow cells by production
of immature WBC
prevents production of RBC & platelets
Chronic leukemia
accumulation of mature WBC in bloodstream because they do
not die
classified by type of WBC that is predominant---monocytic,
lymphocytic.