Physiology of Blood
I.
Components, Characteristics, Functions of Blood
A.
Major Components of Blood
1. formed elements - the actual cellular components
of blood (special connective tissue)
a.
b.
c.
erythrocytes - red blood cells
leukocytes - white blood cells
platelets - cell fragments for clotting
2. blood plasma - complex non-cellular fluid
surrounding formed elements; protein & electrolytes
B.
Separation of Components in a Centrifuge
VOLUME
1.
clear/yellowish PLASMA
55%
2.
thin/whitish buffy coat
middle
with LEUKOCYTES & PLATELETS
<1%
3.
reddish mass - ERYTHROCYTES
bottom
LAYER
top
45%
hematocrit - percentage by VOLUME of erythrocytes when
blood is centrifuged (normal = 45%)
C.
Characteristics of Blood
1.
2.
3.
4.
5.
6.
7.
8.
bright red (oxygenated)
dark red/purplish (unoxygenated)
much more dense than pure water
pH range from 7.35 to 7.45 (slightly alkaline)
slightly warmer than body temperature 100.4 F
typical volume in adult male 5-6 liters
typical volume in adult female 4-5 liters
typically 8% of body weight
1
D.
Major Functions of Blood
1.
Distribution & Transport
a.
oxygen from lungs to body cells
b.
carbon dioxide from body cells to lungs
c.
nutrients from GI tract to body cells
d.
nitrogenous wastes from body cells to
kidneys
e.
hormones from glands to body cells
2.
Regulation (maintenance of homeostasis)
a. maintenance of normal body pH
i.
blood proteins (albumin) & bicarbonate
b. maintenance of circulatory/interstitial fluid
i.
electrolytes aid blood proteins
(albumin)
c. maintenance of temperature (blushed skin)
3.
Protection
a.
platelets and proteins "seal" vessel damage
b.
protection from foreign material &
infections
i. leukocytes, antibodies, complement
proteins
2
II.
Erythrocytes (red blood ells; RBCs)
A.
Structure
1.
7.5 micron diameter; 2.0 micron thick
2.
biconcave disk shape; ideal for gas exchange
i. spectrin - elastic protein; allows shape
change
3.
mature cells are anucleate (no nucleus)
3.
very few organelles; mainly a hemoglobin carrier
i. hemoglobin – 33% of cell mass; carries oxygen
5.
no mitochondria; only anaerobic respiration
6.
ratio erythrocytes:leukocytes = 800:1
7.
red blood cell count: # cells per cubic
millimeter
i. normal male count - 5.1 to 5.8 million
ii. normal female count - 4.3 to 5.2 million
B.
Functions (oxygen & carbon dioxide transport)
1.
hemoglobin - large molecules with globin and
hemes
a.
globin - complex protein with 4 polypeptides
(2 alpha and 2 beta polypeptides)
b.
heme group - IRON containing pigment part of
hemoglobin to which oxygen binds
i. each polypeptide has one heme group;each
heme carries one O2
c. normal hemoglobin levels (grams/l00 ml blood)
i.
infants
14-20 grams/l00 ml
ii
adult female 12-16 grams/100 ml
iii adult male 13-18 grams/l00 ml
2.
states of hemoglobin
a.
oxyhemoglobin - when oxygen is bound to IRON
b.
deoxyhemoglobin - no oxygen bound to IRON
c.
carbaminohemoglobin - when carbon dioxide
bound (to polypeptide chain)
C.
Hematopoiesis and Erythropoiesis
1. hematopoiesis (hemopoiesis) - the maturation,
development and formation of blood cells
a.
red bone marrow (myeloid tissue) - location
of hematopoiesis; in blood sinusoids which
connect with capillaries; mainly in axial
skeleton and heads of femur & humerus
b.
hemocytoblast (stem cell) - the mitotic
precursor to blood cells before
differentiation
3
2.
i. differentiation - maturing cell becomes
"committed" to being certain type blood cell
erythropoiesis - the maturation, development, and
formation of Red Blood Cells (erythrocytes)
hemocytoblast ->proerythroblast -> early
(basophilic) erythroblast -> late (polychromatophilic)
erythroblast -> (hemoglobin) normoblast -> (nucleus
ejected when enough hemoglobin)reticulocyte ->
(retaining some endoplasmic reticulum) ERYTHROCYTE
hemocytoblast -> reticulocyte
reticulocyte -> ERYTHROCYTE
3-5 DAYS
2 DAYS (in
blood)
ERYTHROCYTE lifespan
100-120 DAYS
(primarily destroyed by macrophages in the spleen)
3.
Regulation of Erythropoiesis
a.
hormonal controls - erythropoietin is the
hormone that stimulates RBC production
DECREASED oxygen level in blood causes KIDNEYS to
increase release of erythropoietin
1.
2.
Less RBCs from bleeding
Less RBCs from excess RBC destruction
4
3.
4.
Low oxygen levels (high altitude,
illness)
Increased oxygen demand (exercise)
Eythropoietin now genetically engineered and
synthesized by AMGEN of Thousand Oaks.
Testosterone can also mildly stimulate production of
RBCs in humans
b.
Iron - essential for hemoglobin to carry
oxygen
i.
65% of Fe in body is in hemoglobin
ii. liver and spleen store most excess Fe
bound to ferritin and hemosiderin
iii. Fe in blood bound to transferrin
iv. daily Fe loss: 0.9 mg men/l.7 mg women
v.
women also lose Fe during menstrual
flow
c.
B-complex Vitamins - Vitamin B12 and Folic
Acid essential for DNA synthesis in early mitotic
divisions leading to erythrocytes
D.
Erythrocyte Disorders (Anemias & Polycythemias)
1.
Anemias - a symptom that results when blood has
lower than normal ability to carry oxygen
a.
Insufficient erythrocyte count
i.
hemorrhagic anemia - loss of blood from
bleeding (wound, ulcer, etc.)
ii. hemolytic anemia - erythrocytes rupture
(hemoglobin/transfusion problems,
infection)
iii. aplastic anemia - red marrow problems
(cancer treatment, marrow disease,
etc.)
b.
Decrease in Hemoglobin
i.
iron-deficiency anemia - low Iron
levels (diet; absorption, bleeding,
etc.)
ii. pernicious anemia - low Vitamin B12
(diet, intrinsic factor for Vit B
absorption)
c.
Abnormal Hemoglobin (usually genetic)
i.
thalassemia - easily ruptured RBCs
(Greek & Italian genetic link)
5
ii.
2.
sickle-cell anemia - sickle-shaped RBCs
(genetic Africa, Asia, southern Europe
link)
Polycythemia - excess RBC count, causes thick
blood
a.
polycythemia vera - bone marrow problem;
hematocrit may jump to 80%
b.
secondary polycythemia - high altitude
(normal); or too much erythropoietin release
c.
blood doping in athletes - RBCs previously
withdrawn are transfused before an event;
more RBCs, more oxygen delivery to the body
III. Leukocytes (white blood cells; WBCs)
A.
General Structure and Function
1.
protection from microbes, parasites, toxins,
cancer
2.
1% of blood volume; 4-11,000 per cubic mm blood
3.
diapedesis - can "slip between" capillary wall
4.
amoeboid motion - movement through the body
5.
chemotaxis - moving in direction of a chemical
6.
leukocytosis - increased "white blood cell count"
in response to bacterial/viral infection
7.
granulocytes - contain membrane-bound granules
(neutrophils, eosinophils, basophils)
8.
agranulocytes - NO membrane-bound granules
(lymphocytes, monocytes)
B.
Granulocytes - granules in cytoplasm can be stained with
Wright's Stain; bilobar nuclei; 10-14
micron diameter; all are phagocytic cells (engulf material)
1.
neutrophils - destroy and ingest bacteria & fungi
(polymorphonuclear leuks.; "polys")
a.
most numerous WBC
b.
basophilic (blue) & acidophilic (red)
c.
defensins - antibiotic-like proteins
(granules)
d.
polymorphonuclear - many-lobed nuclei
e.
causes lysis of infecting bacteria/fungi
f.
HIGH poly count --> likely infection
2.
eosinophils - lead attack against parasitic worms
a.
only 1-4% of all leukocytes
b.
two-lobed, purplish nucleus
6
c.
d.
e.
3.
basophils - releases Histamine which causes
inflammation, vasodilation, attraction of WBCs
a.
b.
c.
d.
e.
f.
C.
acidophilic (red) granules with digest
enzymes
phagocytose antigens & antigen/antibody
complex
inactivate chemicals released during
allergies
RAREST of all leukocytes (0.5%)
deep purple U or S shaped nucleus
basophilic (blue) granules with HISTAMINE
related to "mast cells" of connective tissue
BOTH release Histamine with "IgE" signal
antihistamine - blocks the action of
Histamine in response to infection or
allergic antigen
Agranulocytes - WBCs without granules in cytoplasm
1. lymphocytes - two types of lymphocytes
a.
b.
c.
d.
e.
f.
2.
D.
T lymphocytes - (thymus) respond against
virus infected cells and tumor cells
B lymphocytes - (bone) differentiate into
different "plasma cells" which each produce
antibodies against different antigens
lymphocytes primarily in lymphoid tissues
very large basophilic (purple) nucleus
small lymphocytes in blood (5-8 microns)
larger lymphocytes in lymph organs (10-17
mic)
monocytes - differentiate to become macrophages;
serious appetites for infectious microbes
a.
largest of all leukocytes (18 microns)
b.
dark purple, kidney shaped nucleus
Leukopoiesis and Colony Stimulating Factors (CSFs)
1.
2.
leukopoiesis - the production, differentiation,
and development of white blood cells
colony stimulating factors (CSF) - hematopoietic
hormones that promote leukopoiesis
a.
produced by Macrophages and T lymphocytes
i.
macrophage-monocyte CSF (M-CSF)
7
ii.
iii.
iv.
v.
3.
E.
IV.
granulocyte CSF (G-CSF)
granulocyte-macrophage CSF (GM-CSF)
multi CSF (multiple lymphocyte action)
interleukin 3 (IL-3) (general
lymphocytes)
leukopoiesis - all cells derived from
hemocytoblast
Disorders of Leukocytes
1.
leukopenia - abnormally low WBC count
a. HIV infection, glucocorticoids, chemotherapy
2.
leukemia - cancerous condition of "line" of WBCs
a.
myelocytic leukemia (myelocytes)
b.
lymphocytic leukemia (lymphocytes)
c.
acute leukemia - cancer spreads rapidly
d.
chronic leukemia - cancer progresses slowly
e.
anemia, fever, weight loss, bone pain
f.
death from internal hemorrhage or infection
g.
chemotherapy & radiation therapy used to
treat
3.
infectious mononucleosis - caused by Epstein-Barr
virus, excessive monocytes and lymphocytes;
fatigue, sore throat, fever; 3 week course
Platelets (thrombocytes - "clotting")
A.
General Characteristics
1.
2.
3.
4.
B.
very small, 2-4 microns in diameter
approximately 250-500,000 per cubic millimeter
essential for clotting of damaged vasculature
thrombopoietin - regulates platelet production
Formation of Platelets
hemocytoblast-> myeloid stem cell->megakaryoblast->
promegakaryocyte->megakaryocyte-> (large multilobed
nucleus) platelets (anucleated parts of megakaryocyte
cytoplasm)
V.
Plasma (the liquid part of blood)
8
A.
General Characteristics
1.
2.
3.
plasma makes up 55% of normal blood by volume
water is 90% of the plasma by volume
many different SOLUTES in the plasma
a.
albumin - pH buffer & osmotic pressure
b.
globulins - binding proteins & antibodies
c.
clotting proteins - prothrombin & fibrinogen
d.
other proteins - enzymes, hormones, others
e.
nutrients - glucose, fatty acids, amino
acids, cholesterol, vitamins
f.
electrolytes - Na+, K+, Ca++, Mg++, Cl-,
phosphate, sulfate, bicarbonate, others
VI.
Hemostasis (stoppage of blood flow after damage)
A.
General Characteristics
1.
vascular spasms (vasoconstriction at injured
site)
2.
platelet plug formation (plugging the hole)
3.
coagulation (blood clotting - complex mechanism)
B.
Vascular Spasms
1.
first response to vascular injury VASOCONSTRICTION is stimulated by:
a.
b.
c.
C.
compression of vessel by escaping blood
injury "chemicals" released by injured cells
reflexes from adjacent pain receptors
Formation of a
1.
damage to
2.
platelets
3.
platelets
Platelet Plug
endothelium of vessel
become spiky and sticky in response
attach to damaged vessel wall to plug
it
4.
platelets produce thromboxane A2 - granule
release
5.
serotonin release enhances vascular spasm
6.
ADP - attracts and stimulates platelets at site
7.
prostacylin - inhibits aggregation at other sites
VII. Coagulation (blood clotting)
A.
General Events in Clotting
platelet cells activated by damage->
PF3 and/or Tissue Factor produced by platelet cells->
Factor X activated->
9
prothrombin activator (enzyme) produced->
prothrombin conversion
-> thrombin (another enzyme)
thrombin stimulates: fibrinogen----> fibrin mesh
1.
2.
anticoagulant - chemical that inhibits clotting
procoagulant - chemical that promotes clotting
3.
intrinsic pathway - within the damaged vessel
a. more procoagulants needed (I-XIII) toward PF3
and Factor X
b. allows more "scrutiny" before clotting occurs
4.
extrinsic pathway - in outer tissues around
vessel
a. tissue thromboplastin (Tissue Factor) - skips
intrinsic steps straight to PF3 and Fac X
b. allows rapid response to bleeding out of
vessel
(clot can form in 10 to 15 seconds)
5.
After activation of Factor X, common pathway:
Factor X, PF3 (thromboplastin), Factor V, Ca++ -->
prothrombin activator ->
prothrombin converted -> thrombin (active enzyme)
thrombin stimulates: fibrinogen -> fibrin
(meshwork)
Ca++ & thrombin -> Factor XIII (fibrin stabilizer)
B.
Clot Retraction (shrinking of clot)
1.
2.
3.
actomyosin - causes contraction of platelets
blood serum - plasma WITHOUT clotting Factors
platelet-derived growth factor (PDGF) stimulates fibroblast migration and endothelial
growth
C.
Clot Eradication (Fibrinolysis)
1.
healing occurs over 2 - 10 days
2.
tissue plasminogen activator (TPA) - causes the
activation of plasminogen
3.
plasminogen--> plasmin
4.
plasmin degrades proteins within the clot
D.
Factors Limiting Growth and Formation of Clots
1.
Limiting Normal Clot Growth
a.
blood moves too fast to allow procoagulants
10
b.
factors interfere with normal clotting
i.
prothrombin III - deactivates thrombin
ii. protein C - inhibits clotting Factors
iii. heparin - inhibits thrombin; prevents
adherence of platelets to injured site
VII. Disorders of Hemostasis
A.
Thromboembolytic Disorders (undesirable clotting)
1.
thrombus - blood clot in normal blood vessel
2.
embolus -blood clot/gas bubble floating in blood
a.
TPA, streptokinase - can dissolve a clot
b.
aspirin - inhibits Thromboxane formation
c.
heparin - inhibits thrombin & platelet
deposit
d.
dicumarol - anticoagulant, blocks Vitamin K
B.
Bleeding Disorders
1.
thrombocytopenia - reduced platelet count;
generally below 50,000 per cubic millimeter; can
cause excessive bleeding from vascular injury
2.
impaired liver function - lack of procoagulants
(Clotting Factors) that are made in liver a.
vitamin K - essential for liver to make Clotting
Factors for coagulation
3.
hemophilias - hereditary bleeding disorders that
occur almost exclusively in males
a.
hemophilia A - defective Factor VIII (83%)
b.
hemophilia B - defective Factor IX (10%)
c.
Genentech. Inc. - now produces genetically
engineered TPA and Factor VIII; patients do not need
transfusions as often
VIII.
A.
B.
Blood Transfusions and Blood Typing
Transfusion of Blood
1.
whole blood transfusion - all cells and plasma;
anticoagulants (citrate and oxalate salts) used
2.
packed red blood cells - most of the plasma has
been removed prior to transfusion
Human Blood Groups
1.
agglutinogens - glycoproteins on the surface of
blood cells; causes "agglutination" (clumping)
2.
ABO Blood Groups - determined by presence or
absence of Type A and Type B agglutinogen
proteins on cell membrane
11
3.
agglutinins - antibodies against either A or B
agglutinogen (whichever is not present) a.
transfusion reaction - patient's antibodies
attack the donor blood
i.
A (anti-B) receives A,O (not B)
ii. B (anti-A) receives B,O (not A)
iii. AB (none) receives A, B, AB, O
universal recipient
iv. O (anti-A,anti-B) receives O universal
donor
b.
agglutination - when incorrect blood
transfused, antibodies will "clump" new
blood
c.
hemolysis - after clumping, RBCs may
rupture, releasing hemoglobin, harming
kidney
i. dilute hemoglobin, administer diuretics
4.
Rh factor - a different group of agglutinogens
a.
Rh positive (Rh+) - an Rh factor is present
b.
Rh negative (Rh-) - NO Rh factor
c.
transfusion reaction - delayed and less
severe than in ABO confrontation
d.
erythroblastosis fetalis - Rh- mother
antibodies attack Rh+ of older newborn;
results in anemia and low oxygen levels
(hypoxia)
i.
RhoGAM - serum with anti-Rh agglutinins
which will clump the Rh factor,
blocking the reaction of mothers
antibodies
ii. exchange transfusion - directly from
the mother (Rh-) to the newborn (Rh+)
5.
Blood Typing - mixing Donors Blood with Recipient
Antibodies (Anti-A, Anti-B,
anti-Rh)
in order to identify agglutination
Expanding Blood Volume to Avoid Shock
a.
pure plasma without antibodies
b.
plasma expanders - purified human serum
albumin, plasminate, dextran
6.
12
c.
7.
isotonic saline - normal electrolyte
solution isotonic to blood plasma (Ringer's
Solution)
Diagnostic Blood Tests
a.
anemia - low hematocrit (below 35%)
b
lipidemia - high in fat; yellowish plasma
c.
diabetes - blood glucose level
d.
infection - generally higher WBC count
e.
leukemia - significantly higher WBC count
f.
differential WBC count - counts % of each of
the different leukocytes (helps diagnose)
g.
prothrombin time - time for clotting to
occur
h.
platelet count - diagnose thrombocytopenia
i.
complete blood count - overall blood review
13
Heart Physiology
I. Cardiac Muscle (compare to Skeletal Muscle)
light "endomysium"
Cardiac Muscle Cells
medium vasculature
less mitochondria (2%)
fairly short
aerobic & anaerobic
semi-spindle shape
myofibers not fused
branched, interconnected
T tubules at A/I spot
connected (intercalated
discs)
electrical link (gap
junction)
common contraction
(syncytium)
1 or 2 central nuclei
dense "endomysium"
high vasculature
MANY mitochondria (25%
space)
almost all AEROBIC
(oxygen)
myofibers fuse at ends
T tubules wider, fewer
Skeletal Muscle Cells
very long
cylindrical shape
side-by-side
no tight binding
no gap junctions
independent contract
multinucleated
14
II. Mechanism of Contraction of Contractile Cardiac Muscle
Fibers
1.
Na+ influx from extracellular space, causes positive
feedback opening of voltage-gated Na+ channels;
membrane potential quickly depolarizes (-90 to +30
mV); Na+ channels close within 3 ms of opening.
2.
Depolarization causes release of Ca++ from sarcoplasmic
reticulum (as in skeletal muscle), allowing sliding
actin and myosin to proceed.
3.
Depolarization ALSO causes opening of slow Ca++
channels on the membrane (special to cardiac muscle),
further increasing Ca++ influx and activation of
filaments. This causes more prolonged depolarization
than in skeletal muscle, resulting in a plateau action
potential, rather than a "spiked" action potential (as
in skeletal muscle cells).
Differences Between Skeletal & Cardiac MUSCLE Contraction
1.
All-or-None Law - Gap junctions allow all cardiac muscle
cells to be linked electrochemically, so that activation of
a small group of cells spreads like a wave throughout the
entire heart. This is essential for "synchronistic"
contraction of the heart as opposed to skeletal muscle.
2.
Automicity (Autorhythmicity) - some cardiac muscle cells
are "self-excitable" allowing for rhythmic waves of
contraction to adjacent cells throughout the heart.
Skeletal muscle cells must be stimulated by independent
motor neurons as part of a motor unit.
3.
Length of Absolute Refractory Period - The absolute
refractory period of cardiac muscle cells is much longer
than skeletal muscle cells (250 ms vs. 2-3 ms), preventing
wave summation and tetanic contractions which would cause
the heart to stop pumping rhythmically.
III. Internal Conduction (Stimulation)
System of the Heart
A.
General Properties of Conduction
1.
heart can beat rhythmically
without nervous input
15
2.
3.
B.
nodal system (cardiac conduction system) special autorhythmic cells of heart that initiate
impulses for wave-like contraction of entire
heart (no nervous stimulation needed for these)
gap junctions - electrically couple all cardiac
muscle cells so that depolarization sweeps across
heart in sequential fashion from atria to
ventricles
"Pacemaker" Features of Autorhythmic Cells
1.
pacemaker potentials - "autorhythmic cells" of
heart muscle create action potentials in rhythmic
fashion; this is due to unstable resting
potentials which slowly drift back toward
threshold voltage after repolarization from a
previous cycle.
Theoretical Mechanism of Pacemaker Potential:
a.
K+ leak channels allow K+ OUT of the cell more slowly
than in skeletal muscle
b.
Na+ slowly leaks into cell, causing membrane potential
to slowly drift up to the threshold to trigger Ca++
influx from outside (-40 mV)
c.
when threshold for voltage-gated Ca++ channels is
reached (-40 mV), fast calcium channels open,
permitting explosive entry of Ca++ from of the cell,
causing sharp rise in level of depolarization
d.
when peak depolarization is achieved, voltage-gated K+
channels open, causing repolarization to the "unstable
resting potential"
e.
cycle begins again at step a.
C.
Anatomical Sequence of Excitation of the Heart
1. Autorhythmic Cell Location & Order of Impulses
(right atrium) sinoatrial node (SA) -> (right AV
valve)
atrioventricular node (AV) >atrioventricular bundle (bundle of His) ->right &
left bundle of His branches -> Purkinje fibers of
ventricular walls
16
(from SA through complete heart contraction = 220 ms =
0.22 s)
D.
a.
sinoatrial node (SA node) "the pacemaker" - has the
fastest autorhythmic rate (70-80 per minute), and sets
the pace for the entire heart; this rhythm is called
the sinus rhythm; located in right atrial wall, just
inferior to the superior vena cava
b.
atrioventricular node (AV node) - impulses pass from
SA via gap junctions in about 40 ms.; impulses are
delayed about 100 ms to allow completion of the
contraction of both atria; located just above
tricuspid valve (between right atrium & ventricle)
c.
atrioventricular bundle (bundle of His) - in the
interATRIAL septum (connects L and R atria)
d.
L and R bundle of His branches - within the
interVENTRICULAR septum (between L and R ventricles)
e.
Purkinje fibers - within the lateral walls of both the
L and R ventricles; since left ventricle much larger,
Purkinjes more elaborate here; Purkinje fibers
innervate “papillary muscles” before ventricle walls
so AV can valves prevent backflow
Special Considerations of Wave of Excitation
1.
2.
3.
4.
5.
6.
7.
initial SA node excitation causes contraction of both
the R and L atria
contraction of R and L ventricles begins at APEX of
heart (inferior point), ejecting blood superiorly to
aorta and pulmonary artery
the bundle of His is the ONLY link between atrial
contraction and ventricular contraction; AV node and
bundle must work for ventricular contractions
since cells in the SA node has the fastest
autorhythmic rate (70-80 per minute), it drives all
other autorhythmic centers in a normal heart
arrhythmias - uncoordinated heart contractions
fibrillation - rapid and irregular contractions of the
heart chambers; reduces efficiency of heart
defibrillation - application of electric shock to
heart in attempt to retain normal SA node rate
17
8.
9.
10.
11.
E.
ectopic focus - autorhythmic cells other than SA node
take over heart rhythm
nodal rhythm - when AV node takes over pacemaker
function (40-60 per minute)
extrasystole - when outside influence (such as drugs)
leads to premature contraction
heart block - when AV node or bundle of His is not
transmitting sinus rhythm to ventricles
External Innervation Regulating Heart Function
1.
2.
heart can beat without external innervation
external innervation is from AUTONOMIC SYSTEM
parasympathetic - (acetylcholine) DECREASES rate of
contractions
cardioinhibitory center (medulla) -> vagus nerve
(cranial X) -> heart
sympathetic - (norepinephrine) INCREASES rate of
contractions
cardioacceleratory center (medulla) -> lateral horn of
spinal cord to preganglionics Tl-T5 -> postganlionics
cervical/thoracic ganglia -> heart
IV.
Electrocardiography: Electrical Activity of the Heart
A.
Deflection Waves of ECG
1.
P wave - initial wave, demonstrates the
depolarization from SA Node through both ATRIA;
the ATRIA contract about 0.1 s after start of P
Wave
2.
QRS complex - next series of deflections,
demonstrates the depolarization of AV node
through both ventricles; the ventricles contract
throughout the period of the QRS complex, with a
short delay after the end of atrial contraction;
repolarization of atria also obscured
3.
T Wave - repolarization of the ventricles (0.16
s)
18
V.
4.
PR (PQ) Interval - time period from beginning of
atrial contraction to beginning of ventricular
contraction (0.16 s)
5.
QT Interval the time of ventricular contraction
(about 0.36 s); from beginning of ventricular
depolarization to end of repolarization
The Normal Cardiac Cycle
A.
General Concepts
1.
2.
3.
B.
systole - period of chamber contraction
diastole - period of chamber relaxation
cardiac cycle - all events of systole and
diastole during one heart flow cycle
Events of Cardiac Cycle
1.
mid-to-late ventricular diastole: ventricles
filled
*
the AV valves are open
*
pressure: LOW in chambers; HIGH in
aorta/pulmonary trunk
*
aortic/pulmonary semilunar valves CLOSED
*
blood flows from vena cavas/pulmonary vein INTO
atria
*
blood flows through AV valves INTO ventricles
(70%)
*
atrial systole propels more blood > ventricles
(30%)
*
atrial diastole returns through end of cycle
2.
ventricular systole: blood ejected from heart
*
filled ventricles begin to contract, AV valves
CLOSE
isovolumetric contraction phase - ventricles
CLOSED
contraction of closed ventricles increases
pressure
ventricular ejection phase - blood forced out
semilunar valves open, blood -> aorta & pulmonary
trunk
*
*
*
*
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3.
isovolumetric relaxation: early ventricular
diastole
*
ventricles relax, ventricular pressure becomes
LOW
semilunar valves close, aorta & pulmonary trunk
backflow
dicrotic notch - brief increase in aortic
pressure
*
*
TOTAL CARDIAC CYCLE TIME
(normal 70 beats/minute)
=
0.8 second
atrial systole (contraction)
ventricular systole (contraction)
quiescent period (relaxation)
=
=
=
0.1 second
0.3 second
0.4 second
20
VI.
Heart Sounds: Stethoscope Listening
A.
Overview of Heart Sounds
1.
2.
3.
4.
lub-dub, - , lub, dub, lub - closure of AV valves, onset of ventricular
systole
dub - closure of semilunar valves, onset of
diastole
pause - quiescent period of cardiac cycle
21
5.
B.
tricuspid valve (lub) - RT 5th intercostal,
medial
6.
mitral valve (lub) - LT 5th intercostal, lateral
7.
aortic semilunar valve (dub) - RT 2nd intercostal
8.
pulmonary semilunar valve (dub) - LT 2nd
intercostal
Heart Murmurs
1.
2.
3.
murmur - sounds other than the typical "lub-dub";
typically caused by disruptions in flow
incompetent valve - swishing sound just AFTER the
normal "lub" or "dub"; valve does not completely
close, some regurgitation of blood
stenotic valve - high pitched swishing sound when
blood should be flowing through valve; narrowing
of outlet in the open state
VII. Cardiac Output - Blood Pumping of the Heart
A.
General Variables of Cardiac Output
1.
2.
3.
Cardiac Output (CO) - blood amount pumped per
minute
Stroke Volume (SV) - ventricle blood pumped per
beat
Heart Rate (HR) - cardiac cycles per minute
CO (ml/min) =
HR (beats/min)
X
SV (ml/beat)
normal CO = 75 beats/min X 70 ml/beat=5.25 L/min
B.
Regulation of Stroke Volume (SV)
1.
2.
end diastolic volume (EDV) - total blood
collected in ventricle at end of diastole;
determined by length of diastole and venous
pressure (~ 120 ml)
end systolic volume (ESV) - blood left over in
ventricle at end of contraction (not pumped out);
determined by force of ventricle contraction and
arterial blood pressure (~50 ml)
SV (ml/beat)
normal SV =
3.
=
EDV (ml/beat) ESV (ml/beat)
120 m1/beat-50 ml/beat = 70 ml/beat
Frank-Starling Law of the Heart - critical factor
for stroke volume is "degree of stretch of
22
cardiac muscle cells"; more stretch = more
contraction force
a.
increased EDV = more contraction force
i.
ii.
C.
slow heart rate = more time to fill
exercise = more venous blood return
Regulation of Heart Rate (Autonomic, Chemical, Other)
1.
Autonomic Regulation of Heart Rate (HR)
a.
b.
c.
d.
sympathetic - NOREPINEPHRINE (NE) increases
heart rate (maintains stroke volume which
leads to increased Cardiac Output)
parasympathetic - ACETYLCHOLINE (ACh)
decreases heart rate
vagal tone - parasympathetic inhibition of
inherent rate of SA node, allowing normal HR
baroreceptors, pressoreceptors - monitor
changes in blood pressure and allow reflex
activity with the autonomic nervous system
2.
Hormonal and Chemical Regulation of Heart Rate
(HR)
a.
b.
c.
*
*
*
*
*
3.
epinephrine - hormone released by adrenal
medulla during stress; increases heart rate
thyroxine - hormone released by thyroid;
increases heart rate in large quantities;
amplifies effect of epinephrine
Ca++, K+, and Na+ levels very important;
hyperkalemia - increased K+ level; KCl used
to stop heart on lethal injection
hypokalemia - lower K+ levels; leads to
abnormal heart rate rhythms
hypocalcemia - depresses heart function
hypercalcemia - increases contraction phase
hypernatremia - HIGH Na+ concentration; can
block Na+ transport & muscle contraction
Other Factors Effecting Heart Rate (HR)
a.
normal heart rate - fetus 140 - 160
beats/minute
female 72 - 80 beats/minute
23
b.
c.
d.
e.
f.
VIII.
A.
1.
male 64 - 72 beats/minute
exercise - lowers resting heart rate (40-60)
heat - increases heart rate significantly
cold - decreases heart rate significantly
tachycardia - HIGHER than normal resting
heart rate (over 100); may lead to
fibrillation
bradycardia - LOWER than normal resting
heart rate (below 60); parasympathetic drug
side effects; physical conditioning; sign of
pathology in non-healthy patient
Imbalance of Cardiac Output & Heart Pathologies
Imbalance of Cardiac Output
congestive heart failure - heart cannot pump
sufficiently to meet needs of the body
a.
coronary atherosclerosis - leads to gradual
occlusion of heart vessels, reducing oxygen
nutrient supply to cardiac muscle cells;
(fat & salt diet, smoking, stress)
b.
high blood pressure - when aortic pressure
gets too large, left ventricle cannot pump
properly, increasing ESV, and lowering SV
c.
myocardial infarct (MI) - "heart cell death"
due to numerous factors, including coronary
artery occlusion
d.
pulmonary congestion - failure of LEFT
heart; leads to buildup of blood in the
lungs
e.
peripheral congestion - failure of RIGHT
heart; pools in body, leading to edema
(fluid buildup in areas such as feet,
ankles, fingers)
B.
Heart Pathologies (Diseases of the Heart)
1.
congenital heart defects - heart problems that
are present at the time of birth
a.
patent ductus arteriosus - bypass hole
between pulmonary trunk and aorta does not
close
2.
sclerosis of AV valves - fatty deposits on
valves; particularly the mitral valve of LEFT
side; leads to heart murmur
3.
decline in cardiac reserve - heart efficiency
decreases with age
24
4.
fibrosis and conduction problems - nodes and
conduction fibers become scarred over time; may
lead to arrhythmias
25
Circulatory Physiology
I.
Factors Involved in Blood Circulation
A.
Blood Flow - the actual VOLUME of blood moving through
a particular site (vessel or organ) over a certain
TIME period (liter/hour, ml/min)
B.
Blood Pressure - the FORCE exerted on the wall of a
blood vessel by the blood contained within
(millimeters of Mercury; mm Hg)
blood pressure = the systemic arterial pressure of large vessels
of the body (mm Hg)
C.
Resistance to Flow (Peripheral Resistance) - the FORCE
resisting the flow of blood through a vessel (usually
from friction)
1.
viscosity - a measure of the "thickness" or
"stickiness" of a fluid flowing through a pipe
a.
b.
V water < V blood < V toothpaste
water flows easier than blood
2.
tube length - the longer the vessel, the greater
the drop in pressure due to friction
3.
friction
D.
tube diameter - smaller diameter = greater
Relation Between Blood Flow, Pressure, Resistance
difference in blood pressure ( P)
Blood Flow (F) =
peripheral resistance (R)
a.
b.
c.
d.
II.
increased
decreased
increased
flow
decreased
P -> increased flow
P -> decreased flow
R (vasoconstriction) -> DECREASED
R (vasodilation) -> INCREASED flow
Systemic Blood Pressure
A.
Blood Pressure Near the Heart
26
1.
2.
3.
4.
5.
HEART produces blood pressure by pumping the
blood
Blood pressure decreases with distance from Heart
systolic arterial blood pressure - pressure in
aorta (& major arteries) in middle of ventricular
contraction (120 mm Hg in healthy adult)
diastolic arterial blood pressure - pressure in
aorta (& major arteries) during ventricular
diastole, when semilunar valves are closed (80 mm
Hg in healthy adult)
mean arterial pressure (MAP) - the "average"
blood pressure produced by the heart (93 mm Hg in
healthy adult)
mean arterial pressure
1/3 pulse pressure
= diastolic pressure
+
**
6.
pulse pressure = systolic pressure diastolic pressure
blood pressure decreases throughout system
L ventricle
-->120 mm Hg
arteries
-->120 - 60 mm Hg
arterioles
-->60 - 40 mm Hg
capillaries
-->40 - 20 mm Hg
venous
-->20 - 10 mm Hg
R atrium -->10 0 mm Hg
7.
venous return - venous blood pressure is so low,
other factors contribute to venous blood flow
a. respiratory pump - breathing action of thorax
"squeezes" blood back toward the heart
b. muscular pump - contraction/relaxation of
skeletal muscles "milk" blood up veins to heart
III. Factors Affecting Blood Pressure
A.
Cardiac Output ( = stroke volume X heart rate)
CO
=SV (ml/beat) x HR (beats/min)
=70 ml/beat x 60 beats/min = 4200 ml/min
1.
2.
3.
increased cardiac output -> increased blood
pressure
increased stroke volume -> increased blood
pressure
increased heart rate
-> increased blood
pressure
27
B.
Peripheral Resistance
1.
2.
C.
IV.
arteriole constriction ---> increased blood
pressure
resistance inversely proportional to the "fourth
power" of the radius change
Blood Volume
1.
hemorrhage 2.
salt/fluid 3.
polycythemia
4.
RBC anemia -
decrease in blood pressure
increase in blood pressure
- increase in blood viscosity
decrease in blood viscosity
Regulation of Blood Pressure
A.
B.
C.
Nervous System Control
1.
control of arteriole diameter
2.
directs blood flow to proper organs and tissues
that need it
3.
REFLEX PATHWAY:
baroreceptors/chemoreceptors/brain --> afferent
nerve fibers
--> medulla (vasomotor center) -->
vasomotor (efferent) nerve fibers --> smooth muscle
of arterioles
Vasomotor Fibers to Smooth Muscle of Arterioles
1.
sympathetic fibers that release norepinephrine
(NE); cause vasoconstriction of arterioles
Vasomotor Center of the Medulla
1.
2.
3.
D.
sympathetic neuron cell bodies in the medulla
receive input from baroreceptors, chemoreceptors,
and brain
vasomotor tone - general constricted state of
arterioles set by vasomotor center
Baroreceptors
1.
2.
blood pressure receptors large arteries (carotid
sinuses, aortic arch, neck/thorax arteries)
send blood pressure information to vasomotor
center of medulla
increased pressure --> decreased pressure -->
inhibits vasomotor center
--> stimulates
vasomotor center -> vasodilation
vasoconstriction
28
E.
Chemoreceptors
1.
F.
G.
located in aortic arch and carotid arteries
a.
carotid and aortic bodies
2.
monitor OXYGEN and pH levels of the blood
low OXYGEN or low pH ------->
increase blood
pressure, return blood to lungs quickly
Higher Brain Centers Control on BP
1.
hypothalamus & cortex also effect vasomotor area
Chemical Controls of Blood Pressure
1.
2.
3.
4.
5.
H.
Renal (Kidney) Regulation
1.
direct regulation - fluid loss through urine
a.
low pressure/volume --> conserve water
b.
high pressure/volume --> release more water
2.
V.
hormones of adrenal medulla - "fight-or-flight"
response to fear; release of norepinephrine and
epinephrine from adrenal medulla; causes
vasoconstriction and increased BP
atrial natriuretic factor (ANF) - secreted by the
atria of the heart, promotes general decline in
blood pressure kidney releasing more Na+ and
water, reducing fluid volume
antidiuretic hormone (ADH) - released by the
hypothalamus, causes increase in blood pressure
by getting the kidneys to conserve water in the
body; e.g. during hypotensive situations
endothelium derived factors
a.
endothelin - strong vasoconstrictor
b.
endothelium derived relaxing factor vasodilation
alcohol - causes vasodilation
renin-angiotensin mechanism
low blood pressure --> release of renin -->
formation of angiotensin II--> vasoconstriction
Release of aldosterone --> Na+/water reabsorption
by kidney)
Variations in Blood Pressure
A.
Measuring Blood Pressure
29
1.
2.
vital signs - blood pressure, pulse, respiratory
rate, and body temperature
auscultory method of blood pressure measurement
a.
b.
c.
d.
B.
Hypotension (below normal blood pressure, < 100/60)
1.
2.
3.
C.
factors - age, physical conditioning, illness
orthostatic hypotension - generally in elderly,
drop in blood pressure during postural changes
chronic hypotension - ongoing low blood pressure
a.
low blood protein levels (nutrition)
b.
Addison’s disease (adrenal cortex
malfunction)
c.
hypothyroidism
d.
also sign of various types of cancer
Hypertension (above normal blood pressure at rest,
140/90)
1.
2.
secondary hypertension - identifiable
disorder
i.
kidney disorders
ii. endocrine (hormone) disorders
iii. arteriosclerosis
Blood Flow in the Body
A.
>
factors - weight, exercise, emotions, stress
chronic hypertension - ongoing high blood
pressure
a.
prevalent in obese and elderly
b.
leads to heart disease, renal failure,
stroke
c.
also leads to more arteriosclerosis
d.
primary hypertension - unidentified source
i.
high Na+, cholesterol, fat levels
ii. clear genetic component (in families)
iii. diuretics - promote water removal
iv. NE blockers - slow vasoconstriction
e.
VI.
“sphygmomanometer” wrapped around upper arm
inflate above systolic pressure of brachial
pressure released, first sounds - systolic
disappearance of sounds - diastolic pr.
General Features
30
1.
2.
3.
4.
5.
B.
delivery of oxygen and removal of carbon dioxide
gas exchange in the lungs
absorption and delivery of nutrients from GI
tract
processing/waste removal in the kidneys
normal blood flow at rest
abdominal organs
24%
skeletal muscle
20%
kidneys
20%
brain
13%
heart
4%
other
15%
Velocity of Blood Flow
1.
velocity directly related to the TOTAL crosssectional area of the vessel(s)
FASTEST
SLOWEST
aorta
arteries
arterioles
capillaries
40-50 cm/s
20-40 cm/s
1-20 cm/s
0.1-1 cm/s
C.
Local Regulation of Blood Flow
1.
autoregulation - regulation of blood flow by
altering arteriole diameter
a.
oxygen and carbon dioxide levels
b.
prostaglandins, histamines, kinins
c.
needy areas --> more blood flow
2.
myogenic response - change in flow through
arteriole in response to stretch of smooth muscle
3.
reactive hyperemia - increase in blood flow to
area where an occlusion has occurred
4.
increased vasculature - results from prolonged
lack of oxygen/nutrients to an area (eg. heart)
D.
Blood Flow to Skeletal Muscles
1.
E.
active (exercise) hyperemia - increased blood
flow to muscles during heavy activity
a.
decreased oxygen and increased lactic acid
b.
visceral organ blood flow is decreased
Blood Flow to The Brain
1.
2.
3.
MUST maintain constant blood flow (750 ml/min)
sensitive to low pH and high carbon dioxide
blood pressure tightly regulated in the brain
31
a.
b.
F.
fainting -> below 60 mm Hg
edema (brain swelling) -> above 180 mm Hg
Blood Flow to The Skin
1.
intimately involved in temperature regulation
increased body temperature -> hypothalamic inhibition
of vasomotor area -> vasodilation of vessels in skin > increased blood flow -> sweating -> (bradykinin ->
more vasodilation)
G.
Blood Flow to the Lungs
1.
2.
H.
short pathway from heart, less pressure required
low oxygen level --> vasoconstriction
Blood Flow to the Heart
1.
2.
blood to coronary arteries during diastole
vasodilation from ADP and carbon dioxide
VII. Blood Flow in the Capillaries
A.
Exchange of Gases and Nutrients
1.
2.
diffusion - all molecules move DOWN the
concentration gradient (from HIGH to LOW) into or
out of the blood
oxygen/nutrients (blood ----> body cells)
carbon dioxide/ wastes(body cells ----> blood)
B.
Fluid Movements
1.
hydrostatic pressure - force from the capillary
wall on the blood itself
a.
filtration pressure - the pressure forcing
fluid and solutes through capillary clefts
2.
osmotic pressure - force driving fluid in the
direction of HIGHER solute concentration
3.
movement out: Hydrostatic pressure > Osmotic
difference
movement in :
Hydrostatic pressure <
Osmotic difference
4.
normal fluid movement 1.5 ml/min in the entire
body
C.
Circulatory Shock
32
1.
2.
3.
4.
circulatory shock - blood pressure gets so low
that blood will not flow adequately
hypovolemic shock - circulatory shock resulting
from loss of fluid (bleeding, diarrhea, burn)
a.
heart rate increases rapidly
b.
general vasoconstriction of vessels
vascular shock - extreme vasodilation causes
sudden drop in blood pressure
a. snake and spider bites with NE blockers
b.
septicemia - bacterial infection
cardiogenic shock - heart is unable to provide
sufficient blood pressure
33
The Immune System: Innate and Adaptive Body Defenses
I. Innate Defenses
A. Surface Barriers: Skin and
Mucosae
1.
Skin, a highly keratinized
epithelial membrane, represents a
physical barrier to most
microorganisms and their enzymes and
toxins.
2.
Mucous membranes line all body
cavities open to the exterior and
function as an additional physical barrier.
3.
Secretions of the epithelial tissues include acidic
secretions, sebum, hydrochloric acid, saliva, and mucus.
B.
Internal Defenses: Cells and Chemicals
34
1.
Phagocytes confront microorganisms that breach the external
barriers.
a. Macrophages are the main phagocytes of the body.
b. Neutrophils are the first responders and become
phagocytic when they encounter infectious material.
c. Eosinophils are weakly phagocytic but are important in
defending the body against parasitic worms.
d. Mast cells have the ability to bind with, ingest, and
kill a wide range of bacteria.
2.
Natural killer cells are able to lyse and kill cancer cells
and virally infected cells before the adaptive immune system has
been activated.
35
Inflammation is a bodily response to cell damage (physical
trauma, intense heat, irritating chemicals, or infection by
viruses, fungi, or bacteria).
The four cardinal signs of inflammation, as described by the
Roman physician and science writer Celsus, are:

Rubor - redness
 Tumor - swelling
 Calor - heat
 Dolor - pain
The fifth sign, which is sometimes present, is loss of
function, or functio laesa - this was originally described and
added to the four signs described by Celsus by another Roman
physician and science writer, Galen, but was popularized in the
1800s by Rudolph Virchow, the "Father of Modern Pathology".
Functions:
 To destroy and remove pathogens and debris.
 To confine pathogens; prevent spread of infection.
 To repair or replace damaged tissue (sets stage for wound
repair).
The release of inflammatory chemicals causes vasodilation,
which increase blood flow to the area, increased vascular
permeability, which allows fluid containing clotting factors and
antibodies to enter the tissues, sensitize and even directly
stimulate pain receptors, and act as chemotactic factors for
phagocytes (neutrophils and macrophages).
A brief explanation of how some of this inflammation/
phagocytosis /complement activation gets started:
Pattern recognition receptors (PRRs) are receptors that
recognized conserved (common) molecular sequences associated
with a number of different pathogens (PAMPs - pathogen
associated molecular patterns). PRRs are found on the surface
and in the cytoplasm of macrophages, dendritic cells, mucosal
epithelial cells, endothelial cells, and lymphocytes. Some
secreted molecules recognize PAMPs and act as PRRs as well.
Secreted PRRs:
Circulating acute phase proteins, like C-reactive protein,
mannose-binding lectin, and complement proteins C3b and C4 bind
to PAMPs on the surface of a number of different pathogens. This
causes opsonization and phagocytosis of the pathogen and
activation of the complement cascade.
36
Cytoplasmic PRRs:
Intracellular receptors recognize nucleic acid sequences,
cell
wall
components
of
gram-positive
and
gram-negative
bacteria, and a number of other pathogen associated molecules.
Interaction with their ligands activates cytokine production and
HLA upregulation.
Phagocytosis Receptors:
Macrophages have cell-surface receptors that recognize
certain PAMPs, including, those containing mannose. When a
pathogen displays a cell surface polysaccharide containing
mannose it is engulfed into a phagosome.
Toll-Like Receptors (TLRs):
Surface membrane receptors that recognize a number of
different PAMPs. There are at least 10 different TLRs.
Binding of the pathogen to the PRRR initiates a signaling
pathway leading to the activation of the transcription factor
NF-κB. NF-κB turns on cytokine genes, such as those for tumor
necrosis
factor-alpha
(TNF-α),
interleukin-1
(IL-1),
and
chemokines, which attract white blood cells to the site. All of
these effector molecules lead to inflammation at the site.
Mast cells, injured tissue cells, neutrophils, lymphocytes,
and basophils all release inflammatory mediators as well.
The release of histamine, kinins, and prostaglandins causes
vasodilation and increased permeability of blood vessels.
Histamine
causes
vasodilation,
increases
vascular
permeability, and is chemotactic for eosinophils.
Kinins cause clotting, vasodilation, increased vascular
permeability, and pain.
 Factor XII (Hageman Factor) is activated by endotoxin, uric
acid, calcium pyrophosphate, and basement membrane proteins
(collagen).
 XIIa activates Factor XI to initiate clotting and cleaves
prekallikrein to kallikrein.
 Kallikrein converts plasminogen to plasmin, HMW kininogen
to bradykinin, and cleaves C5 to release C5a and C5b.
 C5a stimulates inflammation
Arachidonic acid metabolites
Cyclooxygenase products
 Prostaglandins:
 PGE2 increases vascular permeability, sensitizes to pain,
and is pyrogenic.
37

PGI’s cause vasodilation.
 Thromboxanes cause vasoconstriction.
Lipooxygenase products
 Leukotrienes are produced by mast cells, basophils,
macrophages, and eosinophils.
 LTB4 (SRS-A) is chemotactic, causes vasoconstriction, and
increases endothelial stickiness.
 LTC and LTD cause bronchoconstriction, allergy, increase
vascular permeability
Blood clots can form around an abscess to prevent dissemination
of the infection.
Epithelial mucosal cells increase their release of b- defensins
(broad spectrum antimicrobial proteins) when the epithelial
barrier has been breached and the underlying connective tissue
is inflammed.
Chemotaxis of Phagocytes
Phagocytes have the ability to stick to the lining of the blood
vessels (margination, pavementing).
They also have the ability to squeeze through blood vessels
(emigration or diapedesis).
PMNs show up first and release ROI (reactive oxygen
intermediates), like superoxide anions, hydroxyl ions, hydrogen
peroxide, and the enzyme myeloperoxidase, which converts
hydrogen peroxide to hypochlorous acid (HOCl, which dissociates
to H+ and OCl-, the hypocholorite anion, basically bleach). PMNs
also release defensins and are phagocytic.
Pus is the accumulation of damaged tissue and dead microbes,
granulocytes, and some macrophages. Generally macrophages show
up late to clean up the cellular debris (debride the wound) and
set the stage for wound healing.
38
A tissue is repaired when the stroma (supporting tissue) or
parenchyma (functioning tissue) produces new cells.
Stromal repair by fibroblasts produces scar tissue.
39
4.
Antimicrobial proteins enhance the innate defenses by
attacking microorganisms directly or by hindering their ability
to reproduce.
a. Interferons are small proteins produced by virally
infected cells that help protect surrounding healthy cells.
b. There are three types of human interferon: alpha-IFN,
beta-IFN, and gamma-IFN. Recombinant interferons have been
produced.
40
* The mode of action of
alpha-IFN and beta-IFN is
to induce uninfected
cells to produce
antiviral protein (AVPs)
that prevent viral
replication.
* Once produced and
released from virusinfected cells, IFN
diffuses to uninfected
neighboring cells and
binds to surface
receptors, inducing
uninfected cells to
synthesize antiviral
proteins that interfere
with or inhibit viral
replication.
* Interferons are hostcell-specific but not
virus-specific.
* INFs also enhance the activity of phagocytes and natural
killer (NK) cells, inhibit cell growth, and suppress tumor
formation; they may hold promise as clinical tools in AIDS
and cancer treatment once they are more fully understood.
* Gamma-IFN activates neutrophils and macrophages to kill
bacteria and activates Th1 cells, which stimulate cellmediated reactions.
* Lack of gamma-IFN results in activation of Th2 cells,
which are humoral mediators.
* Very high levels of gamma-IFN stimulates NK cells and
CTLs.
c. Complement refers to a group of about 20 plasma proteins that
provide a major mechanism for destroying foreign pathogens in
the body.
41
5.
Fever, or an abnormally high body temperature, is a
systemic response to a bacterial or viral infection.
Bacterial endotoxins and interleukin-1 can induce fever.
A chill indicates a rising body temperature; crisis
(sweating) indicates that the body’s temperature is
falling.
II. Adaptive Defenses
A.
Aspects of the Adaptive Immune Response
1. Specific: The adaptive defenses recognize and destroy
the specific antigen that initiated the response.
2.
Systemic: The immune response is a systemic response;
it is not limited to the initial infection site.
3.
Has Memory: After an initial exposure the immune
response is able to recognize the same antigen and mount a
faster and stronger defensive attack.
42
4.
Humoral immunity is provided by antibodies, which are
produced by plasma cells and are present in the body’s
“humors” or fluids.
Plasma cells arise from B-lymphocytes after B-cell
activation.
5.
Cellular immunity is associated with T-lymphocytes and
has living cells as its protective factor.
43
44
B. Antigens are substances that can mobilize the immune system
and provoke an immune response.
1.
Complete antigens are able to stimulate the activation
process that leads to proliferation of specific lymphocytes
and antibody production; they are recognized by activated
lymphocytes and the antibodies they have stimulated
production of.
2.
Haptens are incomplete antigens that are not capable
of stimulating the immune response, but if they interact
with proteins of the body they may be recognized as
potentially harmful.
3.
Antigenic determinates or epitopes are a specific part
of an antigen that are immunogenic and bind to free
antibodies or activated lymphocytes.
C.
Cells of the Adaptive Immune System: An Overview
1.
Lymphocytes originate in the bone marrow and when
released become immunocompetent in either the thymus (T
cells) or the bone marrow (B cells).
2.
Antigen-presenting cells engulf antigens and present
fragments of these antigens on their surfaces where they
can be recognized by T cells.
45
46
III. Humoral Immune Response
A. The immunocompetent but naive B lymphocyte is activated when
antigens bind to its surface receptors.
1.
Clonal selection is the process of the B cell growing
and multiplying to form an army of cells that are capable
of recognizing the same antigen.
2.
Plasma cells are the antibody-secreting cells of the
humoral response; most clones develop into plasma cells.
3.
The clones that do not become plasma cells develop
into memory cells.
47
B.
Immunological Memory
1.
The primary immune response occurs on first exposure
to a particular antigen with a lag time of about 3–6 days.
2.
The secondary immune response occurs when someone is
reexposed to the same antigen. It is faster, more
prolonged, and more effective.
C.
Active and Passive Humoral Immunity
48
1.
Active immunity occurs when the body mounts an immune
response to an antigen - effector cells and memory cells
are generated.
a. Naturally acquired active immunity occurs when a
person suffers through the symptoms of an infection.
b. Artificially acquired active immunity occurs when a
person is given a vaccine.
2.
Passive immunity occurs when a person is given
preformed antibodies - no lymphocyte activation, no
effector cells, no memory cells.
a. Naturally acquired passive immunity occurs when a
mother’s antibodies enter fetal circulation.
b. Artificially acquired passive immunity occurs when
a person is given preformed antibodies that have been
harvested from another person.
49
D. Antibodies or immunoglobulins are proteins secreted by
plasma cells in response to an antigen that are capable of
binding to that antigen.
1.
The basic antibody structure consists of four looping
polypeptide chains linked together by disulfide bonds.
2.
Antibodies are divided into five classes based on their
structure: IgM, IgG, IgA, IgD, and IgE.
50
3.
Embryonic cells contain a few hundred gene segments that
are shuffled and combined to form all of the different B cells
that are found in the body.
4.
Antibody Targets and Functions
51
a. Complement fixation and activation occurs when
complement binds to antibodies attached to antigens, and
leads to lysis of the cell.
b. Neutralization occurs when antibodies block specific
sites on viruses or bacterial exotoxins, causing them to
lose their toxic effects.
c. Agglutination occurs when antibodies cross-link to
antigens on cells, causing clumping.
d. Precipitation occurs when soluble molecules are crosslinked into large complexes that settle out of solution.
5.
Monoclonal antibodies are commercially prepared antibodies
specific for a single antigenic determinant.
IV. Cell-Mediated Immune Response
A. The stimulus for clonal selection and differentiation of T
cells is binding of antigen, although their recognition
mechanism is different from B cells.
52
1.
T cells must accomplish a double recognition process:
they must recognize both self (an HLA molecule of a body
cell) and nonself (antigen) at the same time. (HLA
molecules are Human Leukocyte Antigens , you may be more
familiar with the term MHC)
2.
T-cells bind and recognize their specific antigen
through an antigen receptor, which is known as the T-cell
receptor (TCR).
The TCR will bind to the antigen it is specific for only
when the antigen is bound to an HLA molecule on the surface
of some other cell.
Human Leukocyte Antigens, or tissue antigens, are
glycoproteins that are present on almost every cell in the
body. HLA molecules have a groove along the top of the
molecule (the peptide binding site) that binds a small
piece of protein, typically between 8 and 15 amino acids
long.
The presence of peptide in the peptide binding site of an
HLA molecule such that T-cell receptors can bind to the
HLA-peptide complex is known as antigen presentation.
There are two classes of HLA molecules, Class I and Class
II.
Class I HLAs are coded for by three different genes,
Class I A, Class I B, and Class I C. Class I molecules
are present on all nucleated cells in the body and are
recognized by CD8+ T-cells.
Class I HLAs present "internal foreign antigens" like
viral antigens and tumor antigens (which look foreign
because they are mutant normal peptides).
Class II HLAs are coded for by three different genes
as well, the DR, DP, and DQ genes. Class II molecules
are present on antigen presenting cells (APCs), which
include macrophages, dendritic cells, and B-cells.
Class II HLAs are recognized by CD4+ T-cells.
53
Class II HLAs present "exogenous foreign antigens",
things that have been phagocytized and broken down
within APCs.
Normally, HLA molecules have a small piece of endogenous selfpeptide, a piece of some normal self protein that has "worn out"
and been recycled, bound to their antigen binding site.
T-cells "dock" with the HLA-peptide complex, recognize it as
"self", and go on about their business. This is called immune
survellience.
If a foreign peptide is bound to the antigen binding site of the
HLA molecule the T-cell will recognize the complex as "foreign"
and respond appropriately.
But - In order to respond to an antigen, the T-cell has to be
activated first.
54
T Cell Activation
a. The first step in T-cell activation is binding of the Tcell to HLA-antigen complex it is specific for on the
surface of an APC (thats why they're called antigen
presenting cells).
b. The second step is the requirement for the T-cell to
recieve a co-stimulatory signal. Co-stimulation may be the
result of interaction of the CD28 protein on the surface of
T-cells and B-7 proteins on the surface of APCs or
stimulation of the T-cells by cytokines, in particular IL2, or a number of other interactions (this is somewhat
simplified, but go with it).
Without co-stimulation the T-cell won't respond to its
antigen - it becomes anergized or tolerized.
Since non-antigen presenting cells don't have costimulatory molecules, like B-7, on their surface they
can't activate T-cells.
The bottom line here is this: In order to become activated,
naive T-cells must contact their specific antigen by
binding between their T-cell receptor and the appropriate
HLA-antigen complex on the surface of an APC.
c. Once activated, a T cell enlarges and proliferates to
form a clone of cells that differentiate and perform
functions according to their T cell class.
55
3.
Cytokines include hormonelike glycoproteins released by
activated T cells and macrophages.
B.
Specific T Cell Roles
1.
Helper T-cells (CD4+)
Th1 secrete IL-2, IFN-g, TNF-ß
Drives cell-mediated responses (stimulates CD8+ T-cells and
high levels of IFN-g will stimulate phagocytes to kill
internal pathogens)
Th1 also secrete IL-3 and GM-CSF to stimulate bone marrow
to produce more leukocytes
Th2 secrete IL-4, IL-5, IL-6, IL-10
Drives humoral responses (stimulates antibody production by
activated B-cells)
Th1 and Th2 cytokines are antagonistic in activity.
The Th1 cytokine IFNg inhibits proliferation of Th2 cells,
while IFNg and IL-2 stimulate B cells to secrete IgG2a and
inhibit secretion of IgG1 and IgE.
56
The Th2 cytokine IL-4 stimulates B cells to secrete IgE and
IgG1; IL-10 inhibits Th1 secretion of IFNg and IL-2; it also
suppresses Class II MHC expression and production of
bacterial killing molecules and inflammatory cytokines by
macrophages.
The balance between Th1 and Th2 activity helps drive the
immune response in the direction of cell-mediated or
humoral immunity.
Antigen presenting cells phagocytize external antigens,
break them down in phagolysomes, and put peptide fragments
in the peptide binding site of Class II HLAs.
The Class II HLA-peptide complex is then moved to the
surface of the APC where it can be recognized by an
appropriate CD4+ T-cell.
The act of phagocytosis will stimulate macrophages to
secrete IL-1, which will co-stimulate CD4+ T-cells when they
bind to the HLA-peptide complex.
When CD4+ T-cells are activated in this way they secrete IL2, which stimulates macrophages, stimulates CD8+ T-cells,
stimulates B-cells, and self stimulates the activated CD4+
T-cells. IL-2 works like a growth factor.
57
58
2.
Cytotoxic T-cells (CD8+)
What about antigen presentation and activation of CD8+ Tcells?
Same deal, except the antigen is presented bound to a Class
I HLA molecule. APCs can take up viral particles by
phagocytizing virally-infected host cells or through gap
junctions between the APC and virally-infected cell.
B7 proteins on APCs bind CD28 on the T-cells and
costimulate them to become activated.
59
CD8+ T-cells kill virally infected cells and tumor cells when
activated by secreting perforin, granzymes, and expressing a
protein called FAS-ligand on their cell surface.

Perforin creates channels in the target cell membrane.

Granzymes enter the target cell through the channels and
turn on enzymes that induce apoptosis in the target cell.

FAS-ligand binds to a receptor protein on the target cell
called FAS. This interaction also stimulates the tartet
cell to undergo apoptosis.
3.
Regulatory T cells release cytokines that suppress the
activity of both B cells and other types of T cells.
May be CD4+ or CD8+
4.
Gamma/delta T cells are found in the intestine and are more
similar to NK cells than other T cells.
5.
Without helper T cells there is no adaptive immune response
because the helper T cells direct or help complete the
activation of all other immune cells.
60
C.
1.
Organ Transplants and Prevention of Rejection
Grafts
a. Autografts are tissue grafts transplanted from one body
site to another in the same person.
b. Isografts are grafts donated to a patient by a
genetically identical individual such as an identical twin.
c. Allografts are grafts transplanted from individuals that
are not genetically identical but belong to the same
species.
d. Xenografts are grafts taken from another animal species.
61
2.
Transplant success depends on the similarity of the tissues
because cytotoxic T cells, NK cells, and antibodies work to
destroy foreign tissues. Tissue typing for HLA matching and
blood typing for ABO matching are important parts of preparing
for transplantation. An example: Tissue typing for bone marrow
transplantation.
V. Homeostatic Balances of Immunity
A. Immunodeficiencies are any congenital or acquired conditions
that cause immune cells, phagocytes, or complement to behave
abnormally.
1.
Severe combined immunodeficiency (SCID) is a
congenital condition that produces a deficit of B and T
cells.
2.
Acquired immune deficiency syndrome (AIDS) cripples
the immune system by interfering with helper T cells.
B. Autoimmune diseases occur when the immune system loses its
ability to differentiate between self and nonself and ultimately
destroys itself. There is often involvement of HLA type in
susceptibility to autoimmune disease.
C. Hypersensitivities, or allergies, are the result of the
immune system causing tissue damage as it fights off a perceived
threat that would otherwise be harmless.
1.
Immediate
hypersensitivities
(Type
I
or
anaphylactic) begin within seconds after contact and
last about half an hour. IgE antibodies bind to the Fc
receptor on basophils and mast cells and when allergen
binds to the IgE molecules and crosslinks them they
cause
degranulation
and
release
of
histamine,
leukotrienes
and
prostaglandins,
which
cause
inflammation.
There
are
two
basic
kinds
anaphylaxis and localized reactions.
of
Systemic anaphylaxis is anaphylactic
counteracted by epinephrine injection.
62
reactions:
shock
and
systemic
can
be
Localized reactions include allergic rhinitis (hay fever)
accompanied by itchy and teary eyes, congestion, coughing
and sneezing; asthma, accompanied by wheezing and shortness
of breath; and hives, a skin rash usually due to food
allergies.
Anaphylactic reactions can be prevented by determination of
the specific allergens that a patient is sensitive to and
injecting small amounts of the allergens over an extended
period of time (desensitization). This causes the
production of blocking antibodies, which are IgG.
The only other treatment is symptomatic, such as with
antihistamines.
63
2.
Subacute hypersensitivities (Types II and III) take 1–
3 hours to occur and last 10–15 hours.
Type II, or cytotxic
Cytotoxic reactions are mediated by IgG or IgM and
complement.
64
The antibodies are directed toward cellular antigens on
foreign cells or foreign antigens on host cells.
The antigen-antibody complexes cause complement fixation
resulting in cell lysis and phagocytosis.
Examples include transfusion reactions and drug induced
hemolysis.
Type III, or immune complex
Antigens involved are not part of host cells but soluble
antigens.
The antigens are bound by IgM or IgG antibodies and the
antigen-antibody complexes precipitate and lodge in
basement membranes.
Complement fixation leads to inflammation and cell lysis.
Example: Glomerulonephritis
Inflammation of the glomeruli due to immune-complex
disease.
Occurs as a sequel to a beta-hemolytic streptococcal
infection (group A).
Antigen-antibody complexes cause inflammation and
damage to the glomerular membrane.
Other Immune Complex Diseases:

Systemic lupus erythematosus

Rheumatoid arthriti
3.
Delayed hypersensitivity reactions take 1–3 days to occur
and may take weeks to go away.
Delayed-type hypersensitivity (TDTH) T-cells are involved.
Sensitized T-cells secrete lymphokines in response to
antigen.
Lymphokines attract macrophages and initiate tissue damage.
Examples:
65

Tuberculin skin test

Allergic contact dermatitis
VI. Developmental Aspects of the Immune System
A.
Embryologic Development
1.
Stem cells of the immune system originate in the liver
and spleen during weeks 1–9 of embryonic development; later
the bone marrow takes over this role.
2.
In late fetal life and shortly after birth the young
lymphocytes develop self-tolerance and immunocompetence.
B. Later in life the ability and efficiency of our immune
system declines.
66
Commonly Asked Questions

What are the advantages of a closed, as compared with an
open, circulatory system?
Two basic types of transport systems – the open and the
closed
circulatory
systemsoccur
in
the
larger
invertebrate animals. Smaller animal do not need transport
systems, for all of their body cells are near internal
cavities or the external environ, In an open circulatory
system, the blood is not completely enclosed with the
vessels, the hearts pump blood through arteries into large
cavities or sinuses, where it mixes wit interstitial fluid
and bathes the cells of the body. The blood is slowly
return to the heart through small pores, called ostia. And
bathes the cell of the body. The blood is slowly returned
to the heart s through small pores called ostia. In a
closed circulatory system, the blood remain within a
completely enclose system of vessel and never comes in a
direct contact with the body cells Material move between
the blood and interstitial fluid through the thin walls of
capillaries.
Circulation is slower in an open system, because with some
of the blood pooled in sinuses, the hearts cannot build up
67
enough pressure to make the blood flow rapidly. In an open
system cannot achieve high rates of oxygen transport that
active animals requires animals with open system are either
quite small and sluggish of use the open system only for
transport of food and wastes and use a different system for
transport of gases. Insects for opens system only transport
of food and wastes and use a different system for transport
of gases, Insects of example, have a separate system of
vessels- the tracheal system – for gas transport, the
insects circulatory system is composed of five muscular
hearts which slowly pump the blood, which contains food and
wastes (except carbon dioxide, hominess and other material
though a system of vessels and open cavities in a forward
and downward direction. the blood bathes the cells of he
body in open cavities below the vessel. Providing the
necessary materials (except oxygen) for cellular activities
and accumulating waste products 8 except carbon dioxide
from the cells. The blood then moves slowly form these
cavities backward and upward to the hearts. Transport is
accelerated during physical activity, when the skeletal l
muscles contact rhythmically, squeeze the cavities and
forcing the blood back toward the hearts.
Invertebrate animals that have open circulatory systems
include the arthropod (such as insects, spiders, crabs and
lobsters, and most mollusks (such as snails, oysters and
clams. Invertebrates with a closed circulatory system
include the annelids such as earthworms and some mollusks
(such as squids)
.

How can a frog or a lizard be very active if its oxygenrich blood mixes with oxygen-poor blood before becoming
available to the body cells?
A frog or a lizard has a single ventricle, which receives
oxygen-poor oxygen –poor blood from the body as well as oxygenrich blood form the lungs, and in the case of a frog, from the
skin. Blood from the ventricle is pumped via one artery to the
lungs (and skin, in the case of a frog) and via another artery
to the rest of the body. In neither animal, however, is there’s
68
complete mixing of the two types of blood in the ventricle, a
frog has ridge of heart tissue hat partially segregates the
ventricle into a left and right side. The ridge divert
unoxygenated blood fro the right atrium to he artery leading to
the lungs and skin and oxygenated blood from the left atrium to
the artery leading to the rest of the body. A lizard has septum,
or wall, in its ventricle that perform the same function, but
perform it much better that the ridge in frog’s ventricle. The
septum almost completely separates the ventricle into a left and
right side there is a very; little mixing of oxygenated and
unoxygenated blood in a lizard’s heart. The active cells of both
a frog and a lizard receive highly oxygenated ventricles.
A
bird or mammals, however, has a greater need for oxygen, because
of the high metabolic demands of endothermy.

What controls heart rate?
The rate at which the heart muscles contract is regulated
in several ways, the main controls is the sino-atrial node or
pacemaker, which’s a small piece of specialized hat muscle
located in the wall of the right atrium. Electrical impulses
emitted at regular interval by this tissue stimulate muscle
contraction the four chambers of the heart. Each impulse travels
through
both
atria,
causing
them
to
contract
almost
simultaneously, and on to another specialized region – the
atrio-ventricular node – which transmits the impulse to both
ventricles simultaneously, the slight delay in the signal
produces a sequence of contrition first the two aria, the then
two ventricle.
A second regulator of heart rate is an area within the
medulla oblongata of the rain. The cardio-inhibitory center in
this area communicates with the Sino trial node via the vagus
nerves, which contain both afferent and efferent axons. The
afferent nerve axons, which originate in the node and terminate
in the cardio-inhibitory center and extend to the sinoatrial
node, can time the node to decrease the rate of heart-muscle
contractions.
The
cardio-inhibitory
center
functions
to
restrains the Sino Arial node, to hold the heart rate in check.
In addition to feedback from the sinoatrial mode, the
cardio-inhibitory center receiver information from sensory
surfaces and higher brain centers. Sensory cells on the internal
69
and external body surfaces transmit information t the center
about such conditions as indigestion, inhalation of irritating
fumes sudden cold temperatures and blood pressure, when the
center receiver the information, it stimulates the efferent
axons of the vagus nerves, which diminish the heart rate certain
emotional l state also stimulate the cardio-inhibitory centers,
many areas of the brain are involved in the regulation of
emotion, but the critical pathway that influences heat rate form
the limbic system to the cardio-inhibitory center.
The cardio-accelerating with the medulla oblongata of the
brain is stimulated by many factors; including the pain
sensations form the skin and anticipation of exercise. Efferent
neurons form the cardio-accelerating center terminate in the
heart muscle themselves, rather than in the sinotarial node.
When the stimulated, these neurons release a neurotransmitter
(norephineprine) that increase both the heart rate and the
stroke volume (amount of blood pumped with each contraction
Hormones also affect the heart rate. Thyroxin, the hormone
secreted
by
thyroid
gland,
increases
the
heart
rate,
Epinephrine. A hormone secreted by the adrenal medullas,
increases both the rate and the stroke volume.

What regulates the
circulatory system.
rate
a
blood
flows
though
the
Animals must be able to adjust the rate of blood flown in
response to changing conditions when cellular activity is low,
as during sleep, the ea of blood flow is lowered to conserve
energy. During strenuous activity, the rate of blood flow must b
e rapid enough to meet the increased demand for exchange of
material between the bloods and more active cells.
The cardiac output, or quantity of blood the heart pumps
per minute, is about 5-liter sin a resting human. Cardiac
outputs is the product of two factors, - the heart rate (number
of contractions per minute) and Stroke volume (amount of blood
ejected from the heart during each contraction)
70
Heart rate is controlled primarily by Sino Arial node, but
also by cardio-inhibitory and cardio-accelerating center within
the medulla oblongata of the brain and by hormones secreted by
the thyroid and adrenal glands.
Stroke volume is controlled by artery diameter. Because the
vessels and the heart form a closed circulatory system, net
volume of blood expelled form the heart during each contraction
can only be increase if the rate at which blood is returned to
the heart undergoes a corresponding increase. As the volume of
blood returning per minute to the heart increases, the muscles
conditions that force blood through the heart becomes stronger.
Blood is returned other heart more rapidly when the blood
pressure is higher i.e. when arteries are more constricted.
Artery diameter is controlled by vasomotor center in the
medulla oblongata in response to carbon dioxide levels in the
blood and by brain centers that control emotions Higher
concentrations of carbon dioxide, a waste product of cellular
respiration, reflect high levels of cellular activity, the
amount of carbon dioxide in the blood detected by neurons in two
vasomotor center, one on each side of the medulla oblongata,
which send electrical-chemical impulses along vasomotor nerves
to the muscles of the arties. High levels of carbon dioxide
cause constriction of the arterial walls, and thus and increase
in blood pressure and amore rapid flow of blood thorough the
circulatory system. Low levels of carbon dioxide product the
opposite effect: the arteries become dilated blood pressure
drops, and blood flow becomes slower.
Finally blood flow is controlled by the brain center that
control the emotions, including the cerebral cortex in the
limbic system, which emits electrochemical impulses that travel
to the vasomotor center of ht medulla oblongata, Certain
emotional states can accelerate the heart rate and constrict the
arteries, other emotion stress can inhibit the heart rate and
dilate the arteries to though the point that the individual
faints, Information is I transmitted from the vasomotor center
71
to the arterial
vessels.
walls,
which
either
constricts
of
dilates
Applications
1. The ECG
As the heart goes through its contraction-relaxation cycle,
waves of depolarization and repolarization pass from the atria
to the ventricular tissue. These waves produce a measurable
electrical current and associated voltage changes. Since
alterations in heart function due to disease are often reflected
units electrical activity patterns, analysis of the patterns has
considerable diagnostic use.
The instrument used to measure heart electrical activity is
called an electrocardiogram, where electrodes are attached to
the body.
These lead to an amplifier where the tiny voltages
are magnified and fed into a recorder. An example of a normal
tracing is shown in the figure. There are five distinct
alterations in voltage, called P,Q,R,S and T for reference.
Notice that the measured voltages are very small, approximately
a thousandth of a volt. In the heart the voltage changes are
nearly a hundred times larger, but the electrocardiograph can
only measure the voltages that reach the surface of the body.
The first small change, the P wave is produced when the
atria depolarize, the depolarization wave travels to the
ventricle where a much larger change occurs, called the QRS
region. The final T wave is produced by the repolarization of
the ventricles. Now, compare the normal tracing with the one
made form a fibrillating heart. Fibrillation occurs when the
heart muscle contractions are irregular and uncoordinated and
often sets in after a severe heart attack. In fact, fibrillation
is the usual cause of death. The ECG clearly shows the random
patterns associated with the fibrillating heart. Of course, this
is an extreme case, the ECG is more often used to diagnose heart
disease sickness subtle changes in the ECG pattern can be
related to specific kinds of heart damage form disease.
72
An example of such an abnormal patter in is called an
atrioventricular block and results when the tissue that normally
conducts the electrical waves from the atria to the ventricles
is damaged by disease to the extent that conduction is impaired.
In a block leak, there is no coordination of contraction between
atrial and ventricles and the heart’s efficiency as a pump is
greatly impaired.

The Pacemaker
Artificial pacemakers. As we age, the heart may lose control
of its beat, the most common cause of this condition is that
conduction between the atria and ventricles is blocked. The
atrium may contract normally at 70 to 80
times per minute,
driven by the pacemaker tissue, but the ventricles beat at their
own rate at 40 to 50 times per minute.
In many instances, it is possible to implant an artificial
pacemaker near the heart. this is a device that delivers a small
electrical shock to the heart at timed intervals, the purpose of
the shock is not so much to initiate heart beat as to
coordinate
the
atrial
and
ventricular
contractions.
For
instance,
the pacemaker can be set so that it produces
ventricular contractions. For instance, the pacemaker can be set
so that it produces a ventricular contraction whenever the atria
contract.
A relates application of our knowledge is the defibrillator,
now found in most hospitals, during fibrillation, waves of
contraction are moving randomly in heart muscle and the problem
is to coordinate them. The defibrillator does this by sending a
single strong electrical shock through the chest wall into the
heart. the heart muscle responds by contracting completely, then
often begins to beat normally under the influenced of its
pacemaker tissue.
73

Sphygmomanometers.
Blood pressure is an important indicator of vascular function
and most of us have had our blood pressure measures. The
instrument is called a sphygmomanometer, and consists of an
inflatable cuff that is calibrated so that a air pressure in the
cuff reads out in millimeters of mercury to operate the devise,
the cuff is wrapped around the upper arm while a stethoscope is
placed at the inner elbow near the artery that supplied blood to
the heart. As the cuff is inflated, the blood pressure in the
artery is overcome so that the artery collapses. Pressure
through the artery in spurts. At this point , a thumping is
heard in the stethoscope as the artery fills and collapses this
is a good estimate of systolic blood pressure. More pressure is
then released and at a second point the thumping sound
disappears when the artery stays open even during diastole.
This pressure is equivalent to the diastolic blood pressure.
74