CARDIOVASCULAR PHYSIOLOGY

1
MKU
BPharm Year 1
2022
• Origin of the heartbeat and the electrical
activity of the heart
ANATOMY
ANATOMY
 Cardiac conduction system
• The parts of the heart normally beat in orderly
sequence:
– Contraction of the atria (atrial systole) is followed
by contraction of the ventricles (ventricular
systole), and during diastole all four chambers are
relaxed
• The cardiac electric activity that triggers heartbeat
originates in a specialized cardiac conduction system
and spreads via this system to all parts of the
myocardium
 Cardiac conduction system
• Atrial systole
–lasts for 0.1 sec
–caused by atrial depolarization
–ejects 25 mL of blood to each ventricle
• Ventricular systole
–lasts for 0.3 sec
–caused by ventricular depolarization
–The left ventricle ejects about 70 ml into the aorta, the
right ventricle ejects the same volume into the
pulmonary trunk
Cardiac conduction system
 Cardiac conduction system
• The structures that make up the conduction system
are the:
– sinoatrial node (SA node)
– internodal atrial pathways
– atrioventricular node (AV node)
– bundle of His and its branches
– Purkinje system
• The conduction system is mostly composed of
modified cardiac muscle that has fewer striations and
indistinct boundaries
Physiologic characteristics of the conduction
cells
• AUTOMATICITY
• EXCITABILITY
• CONDUCTIVITY
• RHYTHMICITY
• CONTRACTILITY
• TONICITY
 Cardiac conduction system
• The SA node is located at the junction of the superior
vena cava with the right atrium
• The AV node is located in the right posterior portion
of the interatrial septum
• There are three bundles of atrial fibers that contain
Purkinje-type fibers and connect the SA node to the
AV node: the anterior, middle, and posterior tracts
 Cardiac conduction system
• The AV node is continuous with the bundle of His,
which gives off a left bundle branch at the top of the
interventricular septum and continues as the right
bundle branch
• The left bundle branch divides into an anterior
fascicle and a posterior fascicle
• The branches and fascicles run subendocardially
down either side of the septum and come into
contact with the Purkinje system, whose fibers
spread to all parts of the ventricular myocardium
 Cardiac conduction system
• The SA node develops from structures on the right
side of the embryo and the AV node from structures
on the left
• This is why in the adult the right vagus is distributed
mainly to the SA node and the left vagus mainly to
the AV node
• Similarly, the sympathetic innervation on the right
side is distributed primarily to the SA node and the
sympathetic innervation on the left side primarily to
the AV node
 Origin and spread of cardiac excitation
• The various parts of the conduction system and,
under abnormal conditions, parts of the
myocardium, are capable of spontaneous discharge
• However, the SA node normally discharges most
rapidly, with depolarization spreading from it to the
other regions before they discharge spontaneously
• The SA node is therefore the normal cardiac
pacemaker, with its rate of discharge determining
the rate at which the heart beats
 Origin and spread of cardiac excitation
• Impulses generated in the SA node pass through the
atrial pathways to the AV node, through this node to
the bundle of His, and through the branches of the
bundle of His via the Purkinje system to the
ventricular muscle
• In humans, depolarization of the ventricular muscle
starts at the left side of the interventricular septum
and moves first to the right across the mid portion of
the septum. The wave of depolarization then spreads
down the septum to the apex of the heart.
 Cardiac muscle potentials
• Myocardial fibers have a resting membrane potential
of approximately −90 mV
• The individual fibers are separated by membranes,
but membrane depolarization spreads radially
through them as if they were a syncytium because of
the presence of gap junctions
• Recorded extracellularly, the summed electrical
activity of all the cardiac muscle fibers is the ECG
 Cardiac muscle potentials
• Characterized by rapid
depolarization (phase
0), an initial rapid
repolarization (phase 1),
a plateau (phase 2), and
a slow repolarization
process (phase 3) that
allows return to the
resting membrane
potential (phase 4)
 Cardiac muscle potentials
• The initial depolarization is due to Na+ influx through
rapidly opening voltage-gated Na+ channels (the Na+
current, INa)
• The rapid repolarization phase is due to inactivation
of voltage-gated Na+ channels
• The plateau phase is produced by Ca2+ influx through
more slowly opening voltage-gated Ca2+ channels
(the Ca2+ current, ICa)
• The repolarization is due to net K+ efflux through
multiple types of K+ channels
 Pacemaker potentials
• Rhythmically
discharging cells have a
membrane potential
that, after each impulse,
declines to the firing
level
• Thus, this prepotential
or pacemaker potential
triggers the next
impulse
 Pacemaker potentials
• At the peak of each
impulse, IK begins and
brings about
repolarization
• IK then declines, and a
channel permeable to
both Na+ and K+ is
activated (Ih)
 Pacemaker potentials
• Because this channel is activated following
hyperpolarization, it is referred to as an “h” channel
and the current through the h channels is called “h”
current (Ih); however, because of its unusual (funny)
activation it has also been dubbed an “f” channel
and the current produced as “funny current.”
 Pacemaker potentials
• As Ih increases, the
membrane begins to
depolarize, forming the
first part of the
prepotential
• When prepotential
reaches the activation
threshold of voltage-
gated Ca2+ channels,
Ca2+ channels then open
 Pacemaker potentials
• There are two types of
these voltage-gated
Ca2+ channels in the
heart, the T (for
transient) channels and
the L (for long-lasting)
channels
 Pacemaker potentials
• The Ca2+ current (ICa)
due to opening of T
channels completes the
prepotential, and ICa due
to opening of L channels
produces the impulse
• Local Ca2+ release from
the SR (Ca2+ sparks) may
also occur during the
prepotential
 Pacemaker potentials
• Stimulation of the
sympathetic cardiac
nerves speeds the
depolarizing effect, and
the rate of spontaneous
discharge increases
• When the cholinergic
vagal fibers to nodal tissue
are stimulated, slope of
the prepotentials is
decreased
 Difference between cardiac and pacemaker
potentials
• The action potentials in the SA and AV nodes are
largely due to Ca2+ influx, with no contribution by
Na+ influx
• Consequently, there is no sharp, rapid depolarizing
spike before the plateau, as there is in other parts of
the conduction system and in the atrial and
ventricular fibers
• In addition, prepotentials are normally prominent
only in the SA and AV nodes
 Difference between cardiac and pacemaker
potentials
• However, “latent pacemakers” are present in other
portions of the conduction system that can take over
when the SA and AV nodes are depressed or
conduction from them is blocked
• Atrial and ventricular muscle fibers do not have
prepotentials, and they discharge spontaneously only
when injured or abnormal
Difference between cardiac and pacemaker
potentials
 Spread of cardiac excitation
• Depolarization initiated in the SA node spreads
radially through the atria, then converges on the AV
node. Atrial depolarization is complete in about 0.1 s
• Because conduction in the AV node is slow, a delay of
about 0.1 s (AV nodal delay) occurs before excitation
spreads to the ventricles
 Spread of cardiac excitation
• From the top of the septum, the wave of depolarization
spreads in the rapidly conducting Purkinje fibers to all
parts of the ventricles in 0.08–0.1 s
• In humans, depolarization of the ventricular muscle starts
at the left side of the interventricular septum and moves
first to the right across the mid portion of the septum
• The wave of depolarization then spreads down the
septum to the apex of the heart, then the posterobasal
portion of the left ventricle and the uppermost portion of
the septum
 Spread of cardiac excitation
TISSUE
SA node 0.05
Atrial pathways 1
AV node 0.05
Bundle of His 1
Purkinje system 4
Ventricular muscle 1
 The electrocardiogram (ECG)
• Each of the cell types in the heart contains a unique
electrical discharge pattern; the sum of these
electrical discharges can be recorded as the
electrocardiogram (ECG or EKG)
• May be recorded by using an active or exploring
electrode connected to an indifferent electrode at
zero potential (unipolar recording) or by using two
active electrodes (bipolar recording)
 ECG
• Depolarization moving toward an active electrode in
a volume conductor produces a positive deflection,
whereas depolarization moving in the opposite
direction produces a negative deflection
 ECG
• A triangle with the heart
at its center (Einthoven
triangle, see below) can
be approximated by
placing electrodes on
both arms and on the left
leg
• These are the three
standard limb leads used
in electrocardiography
 ECG
• Upward deflection
when the active
electrode becomes
positive relative to the
indifferent electrode
• Downward deflection is
written when the active
electrode becomes
negative
 ECG
• The P wave is primarily
produced by atrial
depolarization, the QRS
complex is dominated
by ventricular
depolarization, and the
T wave by ventricular
repolarization
ECG
 ECG
NORMAL DURATIONS (SECONDS, s)
INTERVALS AVERAGE RANGE EVENTS IN HEART
DURING INTERVAL
PR 0.18 0.12-0.20 Atrioventricular
conduction
QRS 0.08 to 0.10 Ventricular
depolarization
QT 0.40 To 0.43 Ventricular action
potential
ST 0.32 … Plateau portion of
ventricular action
potential
 ECG
• Bipolar leads:
– Lead I, II, III
• Unipolar leads
– 6 unipolar chest leads (precordial leads)
designated V1–V6
– 3 unipolar limb leads
• VR (right arm), VL (left arm), and VF (left foot)
• Augmented limb leads, designated by the
letter a (aVR, aVL, aVF), are generally used
ECG
 ECG
• It should be noted that there is considerable
variation in the position of the normal heart, and the
position affects the configuration of the
electrocardiographic complexes in the various leads
 ECG
• The atria are located posteriorly in the chest. The
ventricles form the base and anterior surface of the
heart, and the right ventricle is anterolateral to the
left. Thus, aVR “looks at” the cavities of the ventricles
• Atrial depolarization, ventricular depolarization, and
ventricular repolarization move away from the
exploring electrode, and the P wave, QRS complex,
and T wave are therefore all negative (downward)
deflections
 ECG
• aVL and aVF look at the ventricles, and the
deflections are therefore predominantly positive
 ECG
• There is no Q wave in V1 and V2, and the initial
portion of the QRS complex is a small upward
deflection because ventricular depolarization first
moves across the midportion of the septum from left
to right toward the exploring electrode
• The wave of excitation then moves down the septum
and into the left ventricle away from the electrode,
producing a large S wave
 ECG
• Finally, it moves back along the ventricular wall
toward the electrode, producing the return to the
isoelectric line
• Conversely, in the left ventricular leads (V4–V6) there
may be an initial small Q wave (left to right septal
depolarization), and there is a large R wave (septal
and left ventricular depolarization) followed in V4
and V5 by a moderate S wave (late depolarization of
the ventricular walls moving back toward the AV
junction)