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Chapter 13
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I. Functions and Components
of the Circulatory System
A. Functions of the Circulatory System
1. Transportation
a. Respiratory gases, nutrients, and wastes
2. Regulation
a. Hormonal and temperature
3. Protection
a. Clotting and immunity
B. Major Components of the Circulatory System
1. Cardiovascular system
a. Heart: four-chambered pump
b. Blood vessels: arteries, arterioles, capillaries,
venules, and veins
2. Lymphatic system
a. Lymphatic vessels, lymphoid tissues,
lymphatic organs (spleen, thymus, tonsils,
lymph nodes)
II. Composition of the Blood
A. Introduction
1. Average adult volume is about 5 liters
2. Arterial blood – leaving the heart; bright red,
oxygenated except for blood going to the lungs
3. Venous blood – entering the heart; dark red,
deoxygenated except for blood coming from the
lungs
4. Made of 45% formed elements and 55% plasma
(by volume)
Constituents of blood
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Centrifuged
Blood Sample
Blood Smear
Blood
plasma
Platelets
“Buffy coat”
Formed
elements
Red blood
cells
White blood
cells
B. Plasma
1. Fluid part of blood
a. Water
b. Dissolved solutes
Representative Normal Plasma Values
Representative Normal Plasma Values
2. Plasma proteins
a. Make up 7-8% of the plasma
b. Albumin: creates osmotic pressure to help draw
water from tissues into capillaries to maintain
blood volume and pressure
c. Globulins
1) Alpha and beta globulins – transport lipids and
fat-soluble vitamins
2) Gamma globulins – antibodies that function in
immunity
d. Fibrinogen: helps in clotting after becoming fibrin
1) Serum – blood without fibrinogen
3. Plasma volume
a. Regulatory mechanisms maintain plasma volume
to maintain blood pressure
b. Osmoreceptors in the hypothalamus cause the
release of ADH from the posterior pituitary gland if
fluid is lost
C. Formed elements of the blood
1. Erythrocytes (red blood cells – RBCs)
a. Flattened, biconcave discs
b. Carry oxygen
c. Lack nuclei and mitochondria
d. Count – approximately 5 million/mm3 blood
e. Have a 120-day life span
f. Each contain about 280 million hemoglobin
molecules
g. Iron heme is recycled from the liver and spleen;
carried by transferrin in the blood to the red bone
marrow
h. Anemia – abnormally low hemoglobin or RBC
count
Red Blood Cells
2. Leukocytes (white blood cells – WBCs)
a. Have nuclei and mitochondria
b. Move in amoeboid fashion
c. Diapedesis – movement through the capillary
wall into connective tissue
d. Count – approximately 5000-9000/mm3 blood
e. Types of leukocytes
1) Granular leukocytes: neutrophils, eosinophils,
and basophils
2) Agranular leukocytes: monocytes and
lymphocytes
Blood Cells and Platelets
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Neutrophils
Lymphocytes
Eosinophils
Monocytes
Basophils
Platelets
Erythrocytes
3. Platelets (thrombocytes)
a. Smallest formed element, fragments of large cells
called megakaryocytic
b. Lack nuclei
c. Very short-lived (5−9 days)
d. Clot blood with several other chemicals and
fibrinogen
e. Release serotonin that stimulates vasoconstriction
f. Count – 130,000 – 400,000/mm3 blood
Formed Elements in the Blood
D. Hematopoiesis (hemopoiesis)
1. Process of blood cell formation
a. Hematopoietic stem cells – embryonic cells that
give rise to all blood cells
b. Process occurs in myeloid tissue (red bone
marrow) and lymphoid tissue
c. As cells differentiate, they develop membrane
receptors for chemical signals
2. Erythropoiesis
a. Formation of red blood cells
b. Red bone marrow produces about 2.5 million
RBCs/sec
c. Regulation of erythropoiesis
1) Process stimulated by erythropoietin from the
kidneys that respond to low blood O2 levels
2) Process takes about 3 days
Erythropoiesis, cont
d. Most iron is recycled from old RBCs, the rest
comes from the diet
1) Intestinal iron secreted into blood through
ferroportin channels
2) All iron travels in blood bound to transferrin
3) Major regulator of iron homeostasis is the
hormone hepcidin which removes ferroportin
channels to promote cellular storage of iron and
lowers plasma iron levels
Stages of Erythropoiesis
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Hemocytoblast
(stem cell)
Proerythroblast
Stimulated by
erythropoietin
In bone marrow
(myeloid tissue)
Erythroblast
Normoblast
Nucleus expelled
Reticulocyte
Erythrocytes
Released
into blood
3. Leukopoiesis
a. Formation of white blood cells
b. Cytokines stimulate the production of the different
subtypes
1) Multipotent growth factor-1
2) Interleukin-1
3) Interleukin-3
4) Granuloctye colony stimulating factor
5) Granulocyte-monocyte colony-stimulating factor
Hematopoiesis, cont
4. Thrombopoietin stimulates growth of
megakaryocytes and maturation into platelets
E. Red Blood Cell Antigens and Blood Typing
1. Antigens: found on the surface of cells to help
immune system recognize self cells
2. Antibodies: secreted by lymphocytes in response
to foreign cells
3. ABO system: antigens on erythrocyte cell surfaces
a. Type A - has the A antigen
b. Type B - has the B antigen
c. Type AB - has both the A and B antigens
d. Type O - has neither the A nor the B antigen
The ABO System of Red Blood Cell
Antigens
Red Blood Cell Antigens and Blood Typing,
cont
4. The plasma contains antibodies against the
antigens not present on the RBC
a. Type A – has anti-B antibodies
b. Type B – has anti-B antibodies
c. Type AB – has no antibodies (universal
recipient)
d. Type O – has anti-A and anti-B antibodies
(universal donor)
5. Transfusion reaction - If a person receives the
wrong blood type, antibodies bind to erythrocytes
and cause agglutination.
Agglutination Reaction
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Type A
Antigens on
red blood
cells
Antibodies
in plasma
Agglutination
reaction
Type B
Agglutination can be used for blood typing.
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Anti-B
Anti-A
Type A
Type B
Type AB
(all): © Stuart Fox
6. Rh factor
a. Antigen D
b. Rh-positive has the antigen
c. Rh-negative does not have the antigen; will not
have antibodies unless exposed to Rh+ either
through a blood transfusion or pregnancy
d. Issues in pregnancy - An Rh− mother exposed to
Rh+ fetal blood produces antibodies. This may
cause erythroblastosis fetalis in future
pregnancies as antibodies cross the placenta and
attack fetal RBCs. Rh- mother is treated with
RhoGAM that inactivates the antigens
F. Blood Clotting
1. Hemostasis: cessation of bleeding when a blood
vessel is damaged
2. Damage exposes collagen fibers to blood,
producing:
a. Vasoconstriction
b. Formation of platelet plug
c. Formation of fibrin protein web
3. Platelets and blood vessel walls
a. Intact endothelium secretes prostacyclin and nitric
oxide, which:
1) Vasodilate
2) Inhibit platelet aggregation
b. and CD39, which:
1) Breaks down ADP into AMP and Pi to inhibit
platelet aggregation further
c. Damaged endothelium exposes collagen
1) Platelets bind to collagen.
2)
3)
Von Willebrand factor holds them there.
Platelets recruit more platelets and form a platelet plug by
secreting: (Platelet release reaction)
a) ADP (sticky platelets)
b) Serotonin (vasoconstriction)
c) Thromboxane A (sticky platelets and vasoconstriction)
4) Activated platelets also activate plasma clotting factors
Platelet Aggregation
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Inactive
platelets
PGI2
NO
VWF
ADP
Endothelial cell
AMP
Collagen
CD39
(a)
Activated
platelets
ADP
TxA2
(b)
ADP
Fibrin
(c)
4. Clotting factors: Formation of Fibrin
a. Fibrinogen is converted to fibrin via one of two
pathways:
1) Intrinsic: Activated by exposure to collagen.
Factor XII activates a cascade of other blood
factors.
2) Extrinsic: Initiated by tissue thromboplastin
(factor III). This is a more direct pathway.
Electron micrograph of a Blood Clot
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Red blood
cells
Fibrin
© David M. Phillips/Photo Researchers
Plasma Clotting Factors
Clotting factors: Formation of Fibrin, cont
b. Next, calcium and phospholipids (from the
platelets) convert prothrombin to the active
enzyme thrombin, which converts fibrinogen to
fibrin.
c. Vitamin K is needed by the liver to make several
of the needed clotting factors
The Clotting Pathways
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2
1
Extrinsic pathway
Common
pathway
Activator:
tissue factor
X
VII
Intrinsic pathway
3
Activators:
collagen, glass,
and others
X activated
V complex
(V, X activated,
calcium,
phospholipids)
VII activated
Prothrombin
XII
XII activated
XI
XI activated
Thrombin
IX
VII complex
(VII, tissue
factor,
calcium,
phospholipids)
IX activated
VIII complex
(VIII, IX activated,
calcium, phospholipids)
Fibrinogen
Fibrin
XIII
Fibrin
polymer
Clotting Disorders & Anticoagulants
5. Dissolution of clots
a. Plasmin digests fibrin
b. Clotting can be prevented with certain drugs:
1) Calcium chelators (sodium citrate or EDTA)
2) Heparin: blocks thrombin
3) Coumadin: inhibits vitamin K
III. Structure of the Heart
A. Structure of the Heart
1. Four chambers
a. Right atrium: receives deoxygenated blood from
the body
b. Left atrium: receives oxygenated blood from the
lungs
c. Right ventricle: pumps deoxygenated blood to
the lungs
d. Left ventricle: pumps oxygenated blood to the
body
Structure of the Heart, cont
2. Fibrous skeleton
a. Separates atria from ventricles. The atria
therefore work as one unit, while the ventricles
work as a separate unit.
b. Forms the annuli fibrosi rings, which hold in
heart valves
B. Pulmonary and Systemic Circulations
1. Pulmonary: between heart and lungs
a. Blood pumps to lungs via pulmonary arteries.
b. Blood returns to heart via pulmonary veins.
2. Systemic: between heart and body tissues
a. Blood pumps to body tissues via aorta.
b. Blood returns to heart via superior and inferior
venae cavae.
Pulmonary and Systemic Circulations
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Superior
vena cava
Right atrium
Left atrium
Pulmonary artery
O2
CO2
Pulmonary vein
Capillaries
Lung
O2
CO2
CO2
Tricuspid valve
Right ventricle
Inferior
vena cava
Aortic
semilunar
valve
O2
Bicuspid valve
Left ventricle
Aorta
CO2
Capillaries
Tissue cells
Summary of Pulmonary & Systemic Circulations
C. Atrioventricular & Semilunar Valves
1. Atrioventricular (AV) valves: located between the
atria and the ventricles
a. Tricuspid: between right atrium and ventricle
b. Bicuspid or mitral: between left atrium and
ventricle
c. Papillary muscles and chordae tendineae
prevent the valves from everting
2. Semilunar valves: located between the ventricles
and arteries leaving the heart
a. Pulmonary: between right ventricle and
pulmonary trunk
b. Aortic: between left ventricle and aorta
Valves of the Heart
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Pulmonary
semilunar
valve
Aortic
semilunar
valve
Bicuspid
valve (into
left ventricle)
Tricuspid
valve (into
right ventricle)
(a)
Aorta
Superior
vena cava
Right
atrium
Tricuspid
valve
Papillary
muscles
Inferior
vena cava
(b)
Pulmonary
trunk
Pulmonary
semilunar valve
Left atrium
Mitral (bicuspid)
valve
Chordae
tendineae
Interventricular
septum
D. Heart Sounds
1. Produced by closing valves
a. “Lub” = closing of AV valves; occurs at
ventricular systole
b. “Dub” = closing of semilunar valves; occurs at
ventricular diastole
Stethoscope Positions for Heart Sounds
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Aortic
area
Pulmonic
area
Nipple
Tricuspid
area
Bicuspid
(mitral)
area
2. Heart Murmur
a. Abnormal heart sounds produced by abnormal
blood flow through heart.
1) Many caused by defective heart valves.
b. Mitral stenosis: Mitral valve calcifies and impairs
flow between left atrium and ventricle.
1) May result in pulmonary hypertension.
Heart Murmur, cont
c. Incompetent valves: do not close properly
1) May be due to damaged papillary muscles
2) Mitral valve prolapse – most common cause of
chronic mitral regurgitation
d. Septal defects: holes in interventricular or
interatrial septa which allows blood to cross sides.
Abnormal blood flow due to septal defects
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AO
AO
PA
LA
LA
PA
LA
RA
RA
LV
LV
RV
RV
(a)
Septal defect
in atria
(b)
Septal defect
in ventricles
IV. Cardiac Cycle
A. Introduction
1. Cardiac cycle
a. Repeating pattern of contraction and
relaxation of the heart.
b. Systole: contraction of heart muscles
c. Diastole: relaxation of heart muscles
2. End-diastolic volume – total volume of blood in
the ventricles at the end of diastole
3. End-systolic volume – the amount of blood left
in the left ventricle after systole (1/3 of the enddiastolic volume)
Cardiac Cycle
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Systole
0.3 sec
Atria
contract
Diastole
0.5 sec
Atria are
relaxed
B. Pressure Changes During the Cardiac Cycle
1. Ventricles begin contraction, pressure rises, and
AV valves close (lub); isovolumetric contraction
2. Pressure builds, semilunar valves open, and blood
is ejected into arteries.
3. Pressure in ventricles falls; semilunar valves close
(dub); isovolumetric relaxation
4. Dicrotic notch – slight inflection in pressure during
isovolumetric relaxation
5. Pressure in ventricles falls below that of atria, and
AV valve opens. Ventricles fill.
6. Atria contract, sending last of blood to ventricles
Cardiac Cycle and Pressures
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1
Isovolumetric
contraction
Atria
relaxed
0
0.2
Time (seconds)
0.4
0.6
0.8
Systole
Ventricles
contract
120
2
Artery
Pressure (mmHg)
100
Ejection
Atria
relaxed
80
Pressure changes
60
Ventricles
contract
40
3
20
Systole
Diastole
1
5
120
Ventricles
relaxed
4
80
Isovolumetric
relaxtion
Atria
relaxed
Left
ventricle
0
Volume (ml)
AV valves
closed
2
Semilunar valves
closed
Volume changes
4
3
40
Heart sounds
1st
2nd
Rapid filling
Atria
relaxed
3rd
Diastole
Ventricles
relaxed
5
Atria
contract
Ventricles
relaxed
Atrial
contraction
V. Electrical Activity of the Heart
and the Electrocardiogram
A. Introduction
1. Cardiac muscle cells are interconnected by gap
junctions called intercalated discs.
2. Once stimulation is applied, the impulse flows
from cell to cell.
3. The area of the heart that contracts from one
stimulation event is called a myocardium or
functional syncytium.
4. The atria and ventricles are separated electrically
by the fibrous skeleton.
B. Electrical Activity of the Heart
1. Automaticity – automatic nature of the heartbeat
2. Sinoatrial node (SA node) - “pacemaker”;
located in right atrium
3. AV node and Purkinje fibers are secondary
pacemakers of ectopic pacemakers; slower rate
than the “sinus rhythm”
4. Pacemaker potential
a. A slow, spontaneous depolarization; also
called diastolic depolarization – between
heartbeats, triggered by hyperpolarization
b. At −40mV, voltage-gated Ca2+ channels open,
triggering action potential and contraction.
c. Repolarization occurs with the opening of
voltage-gated K+ channels.
Pacemaker & Action Potentials
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+20
K+ channels
Voltage-gated
Ca2+
channels
Millivolts
0
–60
Pacemaker potentials
(HCN channels)
Time
Pacemaker potential, cont
d. Pacemaker cells in the sinoatrial node depolarize
spontaneously, but the rate at which they do so
can be modulated:
1) Epinephrine and norepinephrine increase the
production of cAMP, which keeps cardiac
pacemaker channels open.
a) Called HCN channels – hyperpolarizationactivated cyclic nucleotide-gated channels
b) Speeds heart rate due to Na+ inflow
2) Parasympathetic neurons secrete acetylcholine,
which opens K+ channels to slow the heart rate.
5. Myocardial action potentials
a. Cardiac muscle cells have a resting potential of
−85mV.
b. They are depolarized to threshold by action
potentials from the SA node.
c. Voltage-gated Na+ channels (fast Na+) open, and
membrane potential plateaus at -15mV for
200−300 msec.
1) Due to balance between slow influx of Ca2+ and
efflux of K+
d. More K+ are opened, and repolarization occurs.
e. Long plateau prevents summation and tetanus
Action Potential in a Myocardial Cell
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+ 20
Ca2+ In (slow)
0
Millivolts
– 20
– 40
Na+ In
K+ Out
– 60
– 80
– 100
0
50
100 150 200 250 300 350 400
Milliseconds
6. Conducting tissues of the heart
a. Action potentials spread via intercalated discs
(gap junctions).
b. SA node to AV node to stimulate atrial
contraction
c. AV node at base of right atrium and bundle of
His conduct stimulation to ventricles.
d. In the interventricular septum, the bundle of His
divides into right and left bundle branches.
e. Branch bundles become Purkinje fibers, which
stimulate ventricular contraction.
Conduction System of the Heart
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Interatrial
septum
Sinoatrial node
(SA node)
Right and
left bundle
branches
Atrioventricular
node (AV node)
Atrioventricular
bundle
(bundle of His)
Apex of
heart
Purkinje fibers
Interventricular septum
7. Conduction of Impulses
a. Action potentials from the SA node spread rapidly
1) 0.8–1.0 meters/second
b. At the AV node, things slow down.
1) 0.03−0.05 m/sec
2) This accounts for half of the time delay
between atrial and ventricular contraction.
c. The speed picks up in the bundle of His, reaching
5 m/sec in the Purkinje fibers.
d. Ventricles contract 0.1–0.2 seconds after atria.
8. Excitation-contraction Coupling
a. Ca2+-stimulated Ca2+ release
b. Action potentials conducted along the sarcolemma
and T tubules, open voltage-gated Ca2+ channels
c. Ca2+ diffuses into cells and stimulates the opening
of calcium release channels of the SR
d. Ca2+ (mostly from SR) binds to troponin to
stimulate contraction
e. These events occur at signaling complexes on the
sarcolemma where it is close to the SR
Correlation of myocardial action potential with
myocardial contraction
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Action
potential
+20
Contraction (measured
by tension developed)
0
Millivolts
–20
Relative
refractory
period
–40
Absolute refractory period
–60
–80
A
B
–100
0
50
100
150 200
Milliseconds
250
300
9. Repolarization
a. Ca2+ concentration in cytoplasm reduced by active
transport back into the SR and extrusion of Ca2+
through the plasma membrane by the Na+-Ca2+
exchanger
b. Myocardium relaxes
10. Refractory Periods
a. Because the atria and ventricles contract as single
units, they cannot sustain a contraction.
b. Because the action potential of cardiac cells is
long, they also have long refractory periods before
they can contract again.
Correlation of myocardial action potential with
myocardial contraction – refractory periods
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Action
potential
+20
Contraction (measured
by tension developed)
0
Millivolts
–20
Relative
refractory
period
–40
Absolute refractory period
–60
–80
A
B
–100
0
50
100
150 200
Milliseconds
250
300
C. Electrocardiogram (ECG or EKG)
1. The electrocardiograph records the electrical
activity of the heart by picking up the movement
of ions in body tissues in response to this activity.
a. Does not record action potentials, but results
from waves of depolarization
b. Does not record contraction or relaxation, but
the electrical events leading to contraction and
relaxation
2. Electrocardiogram waves and intervals
a.
b.
c.
d.
e.
P wave - atrial depolarization
P-Q interval – atrial systole
QRS wave - ventricular depolarization
S-T segment - plateau phase, ventricular systole
T wave - ventricular repolarization
Electrocardiogram
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R
Atria Ventricles
contract contract
S–T
segment
ECG
T
P
Q
S
P–R
interval
S–T
interval
QRS complex
(a)
Action
potential of
myocardial
cell in
ventricles
(b)
Membrane poteential (mV)
P–Q
segment
Poteential (mV)
R
R
+1
T
P
0
Q
+20
–90
S
Relationship between impulse conduction and ECG
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R
Q
S
(a)
(e) QRS complex: Ventricles
depolarize and contract
(b)
(f)
T
P
(g) T wave: Ventricles
repolarize and relax
(c) P wave: Atria depolarize
and contract
Depolarization
Repolarization
(d)
3. Electrocardiograph leads
a. Bipolar limb leads record voltage between
electrodes placed on wrists and legs.
1) Lead I: between right arm and right leg
2) Lead II: between right arm and left leg
3) Lead III: between left arm and left leg
Electrocardiograph leads, cont
b. Unipolar leads record voltage between a single
electrode on the body and one built into the
machine (ground).
1) Limb leads go on the right arm (AVR), left arm
(AVL), and left leg (AVF).
2) There are six chest leads.
Electrocardiograph Leads
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Right arm
Left arm
I
RA
II
LA
III
LL
1
2
3
Left leg
6
4
5
Electrocardiograph Leads
4. ECG and Heart Sounds
a. “Lub” occurs after the QRS wave as the AV
valves close
b. “Dub” occurs at the beginning of the T wave as
the SL valves close
ECG, Pressures and Heart Sounds
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0
0.2
Time (seconds)
0.4
0.6
0.8
Pressure in ventricle (mmHg)
120
100
1. Intraventricular
pressure rises
as ventricles
contract
80
60
2. Intraventricular
pressure falls
as ventricles
contract
40
20
0
Systole
ECG
Diastole
R
T
P
P
Q
Q
S
Heart
sounds
1. AV valves
close
S1
S2
2. Semilunar
valves close
VI. Blood Vessels
A. Introduction
1. Types of blood vessels
a. Arteries
b. Arterioles
c. Capillaries
d. Venules
e. Veins
The Structure of Blood Vessels
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Venous Circuit
Arterial Circuit
Large vein
Large artery
Tunica
externa
Tunica externa
Tunica
media
Tunica media
Tunica
interna
Endothelium
Endothelium
Elastic layer
Lumen
Inferior
vena cava
Aorta
Medium-sized vein
Medium-sized artery
Tunica externa
Tunica externa
Tunica media
Tunica media
Tunica interna
Tunica interna
Valve
Arteriole
Venule
Tunica externa
Endothelium
Endothelium
Lumen
Valve
Precapillary
sphincter
Fenestrated
capillary
Endothelial cells
Capillary pores
Basement membrane
Continuous
capillary
Tunica
interna
2. Tunics of blood vessels
1. Tunica interna - inner layer; composed of simple
squamous endothelium on a basement membrane
and elastic fibers
2. Tunica media - middle layer; composed of
smooth muscle tissue
3. Tunica externa - outer layer; composed of
connective tissue
B. Arteries
1. Elastic arteries: closer to the heart; allow stretch
as blood is pumped into them and recoil when
ventricles relax
2. Muscular arteries: farther from the heart; have
more smooth muscle in proportion to diameter;
also have more resistance due to smaller lumina
3. Arterioles: 20−30 µm in diameter; provide the
greatest resistance; control blood flow through the
capillaries
Microcirculation
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Blood
flow
Arteriole
Precapillary
sphincter
Metarteriole (forming
arteriovenous shunt)
Artery
Blood
flow
Venule
Vein
Capillaries
C. Capillaries
1. Smallest blood vessel: 7−10 µm in diameter
2. Single layer of simple squamous epithelium tissue
in wall
3. Where gases and nutrients are exchanged
between the blood and tissues
4. Blood flow to capillaries is regulated by:
a. Vasoconstriction and vasodilation of arterioles
b. Precapillary sphincters
5. Types of Capillaries
a. Continuous capillaries: Adjacent cells are close
together; found in muscles, adipose tissue, and
central nervous system (add to blood-brain
barrier)
b. Fenestrated capillaries: have pores in vessel
wall; found in kidneys, intestines, and endocrine
glands
c. Discontinuous: have gaps between cells; found
in bone marrow, liver, and spleen; allow the
passage of proteins
D. Veins
1. Most of the total blood volume is in veins
2. Lower pressure (2 mmHg compared to 100
mmHg average arterial pressure)
3. Thinner walls than arteries, larger lumen; collapse
when cut
Veins, cont
4. Need help to return blood to the heart:
a. Skeletal muscle pumps: Muscles surrounding
the veins help pump blood.
b. Venous valves: Ensure one-directional flow of
blood
c. Breathing: Flattening of the diaphragm at
inhalation increases abdominal cavity
pressure in relation to thoracic pressure and
moves blood toward heart.
The action of one-way venous valves
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To heart
Valve open
Contracted
skeletal
muscles
To heart
Valve
closed
Vein
Relaxed
skeletal
muscles
Valve
closed
Vein
VII. Atherosclerosis and
Cardiac Arrhythmias
A. Atherosclerosis
1. Most common form of arteriosclerosis (hardening
of the arteries)
a. Contributes to 50% of the deaths due to heart
attack and stroke
b. Plaques protrude into the lumen and reduce
blood flow.
c. Serve as sites for thrombus formation
d. Plaques form in response to damage done to
the endothelium of a blood vessel.
e. Caused by smoking, high blood pressure,
diabetes, high cholesterol
Atherosclerosis
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Thrombus
Plaque
(a)
Cholesterol
crystals
Fat
Ulceration
Endothelium
Smooth
muscle cells
Lumen
of vessel
Tunica media
(b)
a: © Biophoto Associates/Photo Researchers
2. Developing Atherosclerosis
a. Lipid-filled macrophages and lymphocytes
assemble at the site of damage within the tunica
interna (fatty streaks).
b. Next, layers of smooth muscle are added.
c. Finally, a cap of connective tissue covers the
layers of smooth muscle, lipids, and cellular
debris.
d. Progress promoted by inflammation stimulated by
cytokines and other paracrine regulators.
3. Cholesterol and Lipoproteins
a. Low-density lipoproteins (LDLs) carry
cholesterol to arteries.
1) People who consume or produce a lot of
cholesterol have more LDLs.
2) This high LDL level is associated with
increased development of atherosclerosis
Structure of a Lipoprotein
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Cholesterol esters
Phospholipid
Triglycerides
Free
cholesterol
Polypeptides
(apolipoproteins)
Cholesterol and Lipoproteins, cont
b. High-density lipoproteins (HDLs) carry
cholesterol away from the arteries to the liver for
metabolism.
1) This takes cholesterol away from the
macrophages in developing plaques (foam
cells).
2) Statin drugs (e.g., Lipitor), fibrates, and niacin
increase HDL levels.
4. Inflammation in Atherosclerosis
a. Atherosclerosis is now believed to be an
inflammatory disease.
b. C-reactive protein (a measure of inflammation) is
a better predictor for atherosclerosis than LDL
levels.
c. When endothelial cells engulf LDLs, they become
oxidized LDLs that damage the endothelium
d. Antioxidants may be future treatments for this
condition.
5. Ischemic Heart Disease
a. Ischemia is a condition characterized by
inadequate oxygen due to reduced blood flow.
1) Atherosclerosis is the most common cause.
2) Associated with increased production of lactic
acid and resulting pain, called angina pectoris
(referred pain).
3) Eventually, necrosis of some areas of the heart
occurs, leading to a myocardial infarction (heart
attack or MI).
Ischemic Heart Disease, cont
4) Nitroglycerin produces vasodilation
a) Improves blood flow
b) Dead myocardial cells can not be replaced by
mitosis of neighboring cells
c) Reperfusion injury may cause death of
neighboring cells to enlarge the infarct
b. Detecting Ischemia
1) Depression of the S-T segment of an
electrocardiogram
2) Plasma concentration of blood enzymes
a) Creatine phosphokinase – 3-6 hours, return to
normal in 3 days
b) Lactate dehydrogenase – 48-72 hours, elevated
about 11 days
c) Troponin I – today’s most sensitive test
d) Troponin T
Detecting Ischemia – Depression of S-T segment
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R
R
P
T
S
Q
T
P
Q
S
Normal
Ischemia
B. Heart Arrhythmias Detected by ECG
1. Abnormal heart rhythms
a. Bradycardia: slow heart rate, below 60 bpm
b. Tachycardia: fast heart rate, above 100 bpm
c. These heart rhythms are normal if the person is
active, but not normal at rest.
d. Abnormal tachycardia can occur due to drugs or
fast ectopic pacemakers.
Heart Arrhythmias, cont
e. Ventricular tachycardia occurs when
pacemakers in the ventricles make them
contract out of synch with the atria.
f. This condition is very dangerous and can
lead to ventricular fibrillation and sudden
death.
2. Flutter and Fibrillation
a. Flutter: extremely fast (200−300 bpm) but
coordinated contractions
b. Fibrillation: uncoordinated pumping between the
atria and ventricles
Arrhythmias Detected by ECG
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Sinus bradycardia
(a) Sinus tachycardia
Ventricular tachycardia
(b) Ventricular fibrillation
3. Types of Fibrillation
a. Atrial fibrillation:
1) Can result from atrial flutter
2) Atrial muscles cannot effectively contract.
3) AV node can’t keep pace with speed of atrial
contractions, but some stimulation is passed on.
4) Only reduces cardiac output by 15%
5) Associated with increased risk of thrombi,
stroke, and heart failure
Types of Fibrillation, cont
b. Ventricular fibrillation
1) Ventricles can’t pump blood, and victim dies
without CPR and/or electrical defibrillation to
reset the heart rhythm.
2) Caused by circus rhythms – continuous cycling
of electrical waves
3) Refractory period prevented
4) Sudden death progresses from ventricular
tachycardia, through ventricular fibrillation,
ending in astole (straight-line ECG)
4. AV Node Block
a. Damage to the AV node can be seen in
changes in the P-R interval of an ECG.
b. First degree: Impulse conduction exceeds 0.2
secs.
c. Second degree: Not every electrical wave can
pass to ventricles
d. Third degree/complete: No stimulation gets
through. A pacemaker in the Purkinje fibers
takes over, but this is slow (20−40 bpm).
AV Node Block
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QRS
P
QRS
P
T
T
First-degree AV block
R
R
P
P
R
P
QS T
P
R
P
QST
P
R
P
QS T
P
P
QS T
P
QS T
Second-degree AV block
QRS T
QRS T
P
P
P
P
Third-degree AV block
P
P
P
QRS T
P
QRS T
P
P
P
VIII. Lymphatic System
A. Functions of the Lymphatic System
1.
2.
3.
Transports excess interstitial fluid (lymph) from tissues to
the veins
Produces and houses lymphocytes for the immune
response
Transports absorbed fats from intestines to blood
Relation between circulatory & lymphatic systems
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Lymph flow
Lymphatic
capillaries
Pulmonary
capillary
network
Lymph node
Lymphatic
vessels
Lymph node
Blood
flow
Systemic
capillary
network
Lymphatic
capillaries
B. Vessels of the Lymphatic System
1. Lymphatic capillaries: smallest; found within most
organs
a. Interstitial fluids, proteins, microorganisms, and
fats can enter.
2. Lymph ducts: formed from merging capillaries
a. Similar in structure to veins
b. Lymph is filtered through lymph nodes
Relation between blood & lymphatic capillaries
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Interstitial space
Lymph capillary
Capillary
bed
Tissue cells
Venule
Lymph duct
Arteriole
Vessels of the Lymphatic System, cont
3. Thoracic trunk and right lymphatic trunk
a. From merging lymphatic ducts
b. Deliver lymph into right and left subclavian
veins
C. Organs of the Lymphatic System
1. Tonsils, thymus, spleen
2. Sites for lymphocyte production
Organs of the Lymphatic System
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Adenoid
Tonsil
Left subclavian
vein
Thymus
Cervical
lymph nodes
Right lymphatic duct
Right subclavian
vein
Axillary lymph
nodes
Thoracic
duct
Spleen
Bone marrow
Lymphatics of
mammary gland
Cisterna chyli
Mesenteric
lymph nodes
and Peyer’s
patches
Lymph node
Inguinal lymph
nodes