Cardiovascular System

Organ system that circulates blood around the body

• The contraction and relaxation of cardiac muscle of
the heart moves blood through the blood vessels
• The blood vessels:
– move the blood around the body
– allow for the exchange of substances between the
blood and the cells of the body
– Pulmonary circuit
• carries deoxygenated blood from the heart to the
lungs, then carries oxygenated blood back to the
heart
– Systemic circuit
• carries oxygenated blood from the heart to all
other organs of the body, then carries
deoxygenated blood back to the heart
Blood Flow Through the
Cardiovascular System
 Heart Shape and Position

• Located between
lungs
• Base
– broad superior
portion of heart
• Apex
– inferior end, tilts to
the left, tapers to
point
 Heart
• 2 superior chambers
– right and left atria which receive blood from the 2
loops of circulation
• 2 inferior chambers
– right and left ventricles which pump blood into the 2
loops of circulation
• Considered to be a “double pump” because the right
and left sides perform separate tasks
– the right atria and ventricle pumps blood through
the pulmonary circuit
– the left atria and ventricle pumps blood through the
systemic circuit
• Walls between the 2 atria interatrial septum and the 2
ventricles interventricular septum prevent the mixing of
blood between the 2 loops of circulation
 Chamber Systole and Diastole
• Throughout the entire cardiovascular system, blood
only flows from a region of higher blood pressure to a
region of lower blood pressure
• Regions of higher pressure are created as a heart
chamber contracts
• During systole, the size of the chamber decreases and
the pressure within the chamber increases which
ejects the blood out (Boyle’s Law)
• When a chamber wall relaxes, the size of the chamber
increases. The pressure within the chamber
decreases allowing the chamber to fill (Boyle’s Law)
• The 2 atria contract while the 2 ventricles are relaxed
– atria ejects blood into the ventricles
• The 2 atria relax while the 2 ventricles contract
– ventricles eject blood out of the heart through the 2
loops of circulation and back to the atria
 Heart Coverings
• The heart is surrounded by a double membrane
pericardium made of connective tissue
– prevents overfilling of the heart with blood
• Parietal pericardium
– fits loosely around the heart
• Visceral pericardium (epicardium)
– thin superficial layer of the heart
• Pericardial cavity
– filled with pericardial fluid
• allows for the heart to work in a relatively friction-
free environment
 Pericardium
and Heart Wall
 Heart Wall – 3 layers

• Epicardium
– visceral layer of the pericardium
• Myocardium
– cardiac muscle layer
– thickest layer of the heart wall
– contracts (systole) and relaxes (diastole) in a
specific pattern to pump blood through the vascular
circuits
• Endocardium
– inner lining of the heart
– made of epithelial tissue
 Atria and Associated Vessels
• During atrial diastole both atria simultaneously fill
with blood returning to heart from the 2 loops of
circulation
• The right atrium receives oxygen poor blood via the
superior and inferior vena cava returning to the heart
from the systemic loop of circulation and via the
coronary sinus from the blood vessels of the heart
• The left atrium receives oxygen rich blood via the
pulmonary veins returning to the heart from the
pulmonary loop of circulation
• During atrial systole, both atria simultaneously pump
blood into the 2 ventricles
 Ventricles and Associated Vessels
• During ventricular diastole, both ventricles
simultaneously fill with blood from the 2 atria
• During ventricular systole, both ventricles
simultaneously pump blood into the 2 loops of
circulation
– The right ventricle pumps the oxygen poor blood
received from the right atrium into the pulmonary
artery (trunk)
– The left ventricle pumps the oxygen rich blood
received from the left atrium into the aorta
• Blood flows away from the aorta and pulmonary artery
(higher blood pressure) into the systemic and
pulmonary circuits of circulation (lower blood pressure)
 Left vs. Right Ventricle
• The left and the right ventricles
pump the same volume of
blood into the systemic and
pulmonary circuits but at very
different pressures (120 mmHg
vs. 25 mmHg)
• Because the blood that is
ejected from the left ventricle
has a further distance to travel
(head to toes), the outer wall of
the left ventricle is notably
thicker than the right which,
when contracted, produces a
higher blood capable of moving
blood a greater distance.
 Heart Valves
• The heart contains 2 pairs of valves (4) which ensure
a unidirectional blood flow through the heart
• 2 valves are located between the atria and ventricles
– atrioventricular valves
• 2 valves are located between the ventricles and the
great arteries
– semilunar valves
• An open valve allows blood flow
• A closed valve prevents blood flow
• A valve will open and close due to a blood pressure
gradient across it
 Atrioventricular Valves
• Atrioventricular (AV) prevent the backflow of blood
from the ventricles into the atria
– right AV valve = tricuspid (3 cusps)
– left AV valve = bicuspid (2 cusps) or mitral
– valve cusps (flaps) are extensions of the
endocardium
• Both AV valves open and close simultaneously
• AV valves open when the blood pressure in the 2 atria
is greater than the blood pressure in the 2 ventricles
– during ventricular diastole
• AV valves close when the blood pressure in the 2
ventricles is greater than the blood pressure in the 2
atria
– during ventricular systole
– produces the first heart sound (lub)
 Chordae Tendineae and Papillary Muscles

• The cusps of the AV valves are anchored to the lumen

of the ventricles by chordae tendineae
– these tendon-like fibers are attached to papillary
muscles of the ventricles
• finger-like extensions of the myocardium
• Upon systole of the ventricles, the papillary muscles
contract and pull on the chordae tendineae which pull
the cusps of the AV valves downward towards the
lumen of the ventricles, preventing their inversion
Atrioventricular Valve Function
 Semilunar Valves

• Semilunar valves prevent backflow of blood from the

arteries into the ventricles
– left semilunar valve = aortic semilunar valve
– right semilunar valve = pulmonary semilunar valve
• Both semilunar valves open and close simultaneously
• Semilunar valves open when the blood pressure in
the 2 ventricles is greater than the blood pressure in
the 2 arteries (pulmonary trunk and aorta)
– during ventricular systole
• Semilunar valves close when the blood pressure in
the 2 ventricles is less than the blood pressure in the 2
arteries (pulmonary trunk and aorta)
– during ventricular diastole
– produces the second heart sound (dupp)
Semilunar Valve Function
 Pathway of Blood Through the Heart

from the systemic circuit → vena cava → right atrium →

tricuspid valve → right ventricle →
pulmonary semilunar valve → pulmonary trunk →
to the pulmonary circuit
AT THE SAME TIME
from the pulmonary circuit → pulmonary veins →
left atrium → bicuspid valve → left ventricle →
aortic semilunar valve → aorta → to the systemic circuit
 Anatomy of the Myocardium
• Every myocyte in the heart is physically connected to
adjacent cells by integral membrane proteins which
form pores between cells called gap junctions
– the gap junctions are found in large densities at
connections between 2 cardiac myocytes called
intercalated discs
– the gap junctions allow ions to move between the
cytoplasm between 2 joined cells
• creates an electrical synapse
• an AP generated in one myocyte of the heart will
spread to adjacent myocytes until every myocyte
of the heart elicits an AP
Histology of the Myocardium
 The Myocardium
• Working cardiac myocytes
– comprise over 95% of atrial and ventricular mass
– mass of the capable of contraction which moves the
blood through the cardiovascular system
– an AP must be created before it can contract
• Conducting cardiac myocytes
– comprise less than 5% of the myocardial mass
– DO NOT contract (lack sufficient actin and myosin)
– act like a neuron
• act as pacemakers by spontaneously generating
APs (without ANY stimulation by the nervous
system) at a certain frequency (rate) which pace
the heart (autorhythmicity)
• determine the path (roadmap) that the AP will
propagate throughout the heart to coordinate the
pattern of systole and diastole of the working
myocytes in the atria and ventricles
Conducting
Myocytes
 SA Node
• The sinoatrial (SA) node is a small group of
conducting myocytes in the wall of the right atrium
– In a resting adult the SA node initiates an AP
approximately every 0.8 seconds (75 per minute)
determining the frequency (sinus rhythm) of systole
and diastole of the atria and ventricles resulting in a
heart rate of 75 beats per minute (bpm)
– The frequency of the APs can be altered by the
antagonistic branches of the ANS to raise or lower
the heart rate (HR) when appropriate
• the Sympathetic NS increases HR from rest
–when HR > 100 bpm = tachycardia
• the Parasympathetic NS decreases HR from rest
–when HR < 60 bpm = bradycardia
 Spread of the action potential through the heart
• From the SA node, the AP propagates via gap
junctions to the:
– atrial working myocytes, causing atrial systole
which forces blood into the ventricles
– Atrioventricular node
• The atrioventricular (AV) node:
– a second group of conducting myocytes located at
the boundary between the right atrium and the
interventricular septum
– only route for the AP to spread into the ventricles
(can’t go through the valves because they are made
of endothelium lacking gap junctions)
– slows down the speed of the AP propagation
• ensure that the atria finish systole BEFORE the
ventricles begin systole
 Spread of the action potential through the heart
• The AP propagates from the AV node to the Bundle of
His (and bundle branches)
– located within the interventricular septum
– speeds up the speed of the AP propagation
– propagates the AP from the AV node through the
interventricular septum to the apex of the heart to
the Purkinjie fibers
• located within the interventricular septum and the
walls of the rt. and lt. ventricles
• propagates the AP from the bundle branches to
the ventricular working cardiac myocytes within
the interventricular septum and the outer walls of
the right and left ventricles, causing ventricular
systole which forces blood into the pulmonary
trunk and aorta
 Functioning of Working Cardiac Myocytes

• Working cardiac myocytes will ONLY go through

systole followed by diastole AFTER an action potential
has been generated in the myocyte
– note that the electrical event (AP) in the cell
ALWAYS causes the mechanical event
(contraction/relaxation) and is called excitation-
contraction coupling
• The action potential of a working cardiac myocyte
results from the opening and closing of voltage-gated
ion channels in the cell membrane (sarcolemma) and
the resultant diffusion of ions either into or out of the
cell
 Working myocyte action potential
The membrane potential of a working myocyte is
maintained at resting (-70 mV) until it is stimulated by
The action potential has 4 distinct phases

1. Rapid depolarization due to the opening of voltage

gated Na+ channels (inward Na+ flux)
2. Slight repolarization due to closing of voltage gated
Na+ channels (inward Na+ flux stops)
3. Plateau phase due to the opening of voltage gated
Ca2+ channels (inward Ca2+ flux)
4. Repolarization phase due to the opening of voltage
gated K+ channels (outward K+ flux) and closing of
voltage gated Ca2+ channels (inward Ca2+ flux stops)
 Functioning of Working Cardiac Myocytes
• Similar to skeletal myocytes, working cardiac
myocytes contain the contractile proteins actin and
myosin which are arranged in repeating sarcomeres
• Also similar to skeletal myocytes, working cardiac
myocytes have an extensive sarcoplasmic reticulum
(SR) which stores Ca2+ required for contraction
• The Ca2+ that diffuses into the sarcoplasm during the
plateau phase of the action potential stimulates the
release of stored Ca2+ from the SR into the
sarcoplasm
– known as calcium induced calcium release (CICR)
– promotes the interaction between actin and myosin
(cross-bridge cycling) resulting in the contraction
(systole) of the cell
– removal of the Ca2+ from the sarcoplasm results in
the relaxation (diastole) of the cell
Working Myocyte Excitation-Contraction
Coupling
The absolute
refractory period
of the action
potential is
nearly as long
as its contractile
period
– this prevents
twitch
summation
and tetany of
the working
cardiac
myocytes
 Relaxation of a Working Cardiac Myocyte

• Diastole of a working cardiac myocyte results from the

removal of Ca2+ from the sarcoplasm in 2 ways:
– Ca2+-ATPase (primary active transporting protein) in
the SR membrane pumps Ca2+ out of the
sarcoplasm back into the SR (via ATP hydrolysis) to
be ready for the next heart beat
– Na+, Ca2+-exchanger (secondary active transporting
protein) in the sarcolemma which actively transports
Ca2+ out of the sarcoplasm as Na+ diffuses into the
sarcoplasm
 Electrocardiogram

• The electrocardiogram (ECG) is a graphical

representation of the summation of the APs in ALL of
the working cardiac myocytes of the atria and the
ventricles
– relates the depolarization and repolarization of the
atria and the ventricles with respect to time
• There are 3 major waves of the ECG which, follow in
sequence, the spread of the AP from the atria to the
ventricles
– P wave
– QRS Complex
– T wave
ECG
 ECG Waves
• P wave
– simultaneous depolarization of both atria
– a small wave due to a small number of atrial
working cardiac myocytes
• QRS complex
– depolarization of both ventricles
– large wave due to a large number of ventricular
working cardiac myocytes
– the repolarization both atria occurs at this time but
is hidden by much larger ventricular depolarization
• T wave
– repolarization of all ventricular working cardiac
myocytes
 The Cardiac Cycle
• The atria and the ventricles of the heart contract and
relax (mechanical events) in a specific sequence
which results in pressure and volume changes moving
blood through the cardiovascular system.
– the propagation of the AP from the SA node through
the myocardium of the heart (noted on and ECG)
determines the sequence of mechanical events
within the heart chambers
– these electrical and mechanical events repeat every
0.8 seconds in what is called the cardiac cycle
• The cardiac cycle has 4 phases which are associated
with the pressure and volume changes that occur
within the ventricles.
 Phases of the Cardiac Cycle
1. Ventricular filling
2. Isovolumetric contraction
3. Ventricular ejection
4. Isovolumetric relaxation
Cardiac Cycle
 Ventricular Filling
• At the beginning of ventricular filling, the semilunar
valves are closed, BOTH atria and ventricles are in
diastole whereby blood from the great veins pass
through the atria through opened AV valves passively
filling the ventricles (1a and 1b) (accounts for 85% of
ventricular filling)

• The P wave of the ECG causes atrial systole whereby

blood is ejected from the atria to finish the filling of the
diastolic ventricles (1c) (15% of ventricular filling)
• The volume of blood in each ventricle at the end of the
filling phase is called End Diastolic Volume (EDV) and
is approximately 120 mL
 Isovolumetric Contraction
• As atrial systole comes to an end the QRS complex of
the ECG causes ventricular systole, which is
subdivided into a short isovolumetric phase an a
longer ejection phase
• The semilunar valves remain closed while ventricular
pressure rises above atrial pressure causing the AV
valves to close
– the ventricle becomes a closed chamber with no
blood entering or leaving the ventricle as
contraction continues to further increase the
pressure in the ventricles
 Ventricular Ejection
• Ventricular pressure continues to rise until it
overcomes the pressure in the arteries opening the
semilunar valves and ejecting blood into the arteries
• As approximately 2/3 (70 mL) of the blood in the
ventricle is ejected and ventricular contraction comes
to an end, ventricular pressure becomes less than the
pressure in the great arteries causing a backflow of
blood into the ventricles closing the semilunar valves
– semilunar valve closure causes a brief rise in the
arterial pressure called the dicrotic notch as blood
rebounds off the valve cusps
• The volume of blood remaining in the
ventricles (50 mL) is called the
End Systolic Volume (ESV)
 Isovolumetric Relaxation
• Following the closure of the semilunar valves, the
ventricles once again become closed chambers with
no blood entering or leaving, as the AV valves remain
closed.
• As the ventricles continue to relax, the pressure
continues to fall in until it becomes less than the
pressure in the atria causing the AV valves to open
which ends isovolumetric relaxation and begins
ventricular filling.
 Cardiac Output (CO)
• CO is the volume of blood pumped by a single
ventricle in one minute
• Directly related to both the heart rate (HR) and stroke
volume (SV)
• HR is the number of heart beats per minute
– normal resting HR = 75 beats/min
• SV is the volume of blood ejected out by a ventricle
each systole (beat) = EDV ─ ESV
– normal resting SV = 70 ml/beat
• HR x SV = CO
• (75 beats/min) x (70 ml/beat) = 5250 ml/min
= 5.25 L/min
– the entire blood volume is completely circulated
around the body every minute
 The Need to Control Cardiac Output
• The CO can be altered to meet the needs of your body
– deliver O2, nutrients, hormones… to the cells of the
body as quickly as they are used
– remove CO2, urea, lactic acid… from the cells of the
body as quickly as they are produced
• At certain times, the needs of your body change
– skeletal muscles during exercise use O2 and
produce CO2 faster requiring an increase in the
delivery rate of O2 and removal rate of CO2
– during sleep, O2 is used and CO2 is produced more
slowly requiring a decrease in the delivery rate of
O2 and removal rate of CO2
 Alteration of Cardiac Output
• CO can be changed by either changing HR or SV
• If HR or SV increases, the CO increases, sending
blood through the cardiovascular system faster
• If HR or SV decreases, the CO decreases, sending
blood through the cardiovascular system slower
• Both HR and SV are controlled by the 2 antagonistic
branches of the Autonomic Nervous System
• Cardioacceleratory (sympathetic) center in the
medulla oblongata can increase both the HR and SV
• Cardioinhibitory (parasympathetic) center in the
medulla oblongata can decrease the HR only
 Cardiac Centers and Regulation of HR
• APs from the cardioacceleratory center propagate
along the sympathetic cardiac nerve which synapse
with the SA node
– sympathetic neurons exocytose norepinepherine
(an adrenergic agent) onto the SA node
• norepinephrine binds to β-(beta) adrenergic
receptors of SA nodal cells resulting in an
increase in the frequency of APs in the SA node
• APs from the cardioinhibitory center propagate along
the Vagus nerve which synapses with the SA node
– releases the neurotransmitter acetylcholine (a
cholinergic agent) onto the SA node
• acetylcholine binds muscarinic cholinergic
receptors of SA nodal cells resulting in a
decrease in the frequency of APs in the SA node
SA Node Action Potentials
 Regulation of SV
• Ventricular contractility
– the force produced by the working ventricular
myocytes during systole
– controlled by hormones, neurotransmitters and
other chemical substances (drugs)
• The preload on the ventricles
– the force applied to working ventricular myocytes
before they contract
• the amount of pressure in the ventricles at the
end of ventricular filling
• aids ejection of blood out of the ventricles
• The afterload on the ventricles
– the force applied to working ventricular myocytes
after they begin to contract
• the amount of pressure in the arteries pushing on
the closed semilunar valves
• opposes ejection of blood out of the ventricles
 Ventricular Contractility and SV

• The force produced by a single working ventricular

myocyte depends upon the amount of sarcoplasmic
Ca2+ during systole
– large intracellular Ca2+ levels → strong systole →
larger SV
– small intracellular Ca2+ levels → weak systole →
smaller SV
– certain hormones and drugs can alter the amount of
intracellular Ca2+ in working myocytes during
systole
 Chemical Effects on Ventricular Contractility
• Epinephrine and norepinephrine bind to β-adrenergic
receptors on working myocytes causing the opening of
additional Ca2+ channels in the cell membrane
– increases sarcoplasmic Ca2+ increasing the SV
• “β blockers” prevent the binding to the β receptors
– decreases intracellular Ca2+ decreasing the SV
• “Ca2+ channel blockers” (Verapamil) block some of the
Ca2+ channels in the cell membrane that open during
the plateau phase of the AP (interferes with CICR)
– decreases intracellular Ca2+ increasing the SV
• “Cardiac glycosides” (digoxin/digitalis) inhibits the
Na+,K+-ATPase decreasing the Na+ gradient across
the cell membrane of the myocyte
– decreases the removal of Ca2+ from the sarcoplasm
by the Na+,Ca2+-exchanger
• increases intracellular Ca2+ increasing the SV
 Preload, the Starling Law of the Heart and SV
• The more working ventricular
cardiac myocytes are
stretched, the harder they
contract. This stretch is
determined by the amount of
blood in the ventricle before it
contracts (EDV).
• The amount of blood that
enters the ventricle during
filling depends on factors such
as venous pressure, blood
volume and atrial contractility
– If the EDV increases the SV
will increase
– If the EDV decreases the SV
will decrease
 Afterload and the SV
• Arterial blood pressure
opposes the ejection of blood
from the ventricles by pushing
against closed semilunar
valves
• The afterload and the SV are
inversely proportional
– if the afterload increases
the SV decreases
– if the afterload decreases
the SV increases
• The arterial blood pressure
depends on factors such as
blood volume, arterial
compliance and arterial
vasoconstriction/vasodilation