Cardiovascular
Physiology
Cardiovascular Physiology:
Enrichment
Prof. Mark A.W. Andrews, Ph.D.
Prof. Mark Andrews, Ph.D.
1
Cardiovascular
Physiology
Cardiac Layers
• epicardium (visceral pericardium)
– serous membrane covering heart
– adipose in thick layer in some places
– coronary blood vessels travel through this
layer
Pericardial
cavity
Pericardial
sac:
• endocardium
– smooth inner lining of heart and blood
vessels
– covers the valve surfaces and continuous
with endothelium of blood vessels
Fibrous
layer
Serous
layer
Epicardium
• myocardium
– layer of cardiac muscle proportional to
work
– muscle spirals around heart which
produces wringing motion
•
fibrous skeleton of the heart -
framework of collagenous and elastic fibers
– provides structural support and attachment
for cardiac muscle and anchor for valve
tissue
– electrical insulation between atria and
ventricles important in timing and
coordination of contractile activity
Prof. Mark Andrews, Ph.D.
Myocardium
Endocardium
Epicardium
Pericardial sac
2
Cardiovascular
Physiology
Heart Chambers
CO2
O2
•
four chambers
–
right and left atria
•
•
•
–
O2-poor,
CO2-rich
blood
right and left ventricles
•
•
Pulmonary circuit
O2-rich,
CO2-poor
blood
–
•
Systemic circuit
Prof. Mark Andrews, Ph.D.
Near fully saturated (96-98%) blood arrives from lungs via
pulmonary veins
Blood is sent to all organs of the body via aorta
right side of heart
•
•
CO2
Two inferior chambers
Pump blood into arteries
left side of heart
•
–
Two superior chambers
Receive blood returning to heart
surface auricles (seen on surface)
Lesser oxygenated blood (70-75%) arrives from inferior
and superior vena cava
Blood is sent to lungs via pulmonary trunk
O2
3
Heart Valves
Cardiovascular
Physiology
• valves ensure a one-way flow of blood through the heart
• atrioventricular (AV) valves – controls blood flow
between atria and ventricles
– right AV valve has 3 cusps (tricuspid valve)
– left AV valve has 2 cusps (mitral or bicuspid valve)
– chordae tendineae - cords connect AV valves to papillary
muscles on floor of ventricles
• prevent AV valves from flipping inside out or bulging into the atria
when the ventricles contract
• semilunar valves - control flow into great arteries –
open and close because of blood flow and pressure
– pulmonary semilunar valve - in opening between right
ventricle and pulmonary trunk
– aortic semilunar valve in opening between left ventricle and
aorta
Prof. Mark Andrews, Ph.D.
4
Cardiovascular
Physiology
•
Heart Valves
fibrous skeleton of the heart - framework of collagen and elastin fibers
– provides structural support and attachment for cardiac muscle and anchor for valve tissue.
– Acts in electrical insulation between atria and ventricles for coordination of contractile activity.
Left AV
(bicuspid) valve
Right AV
(tricuspid) valve
Fibrous
skeleton
Openings to
coronary arteries
Aortic
valve
Pulmonary
valve
Prof. Mark Andrews, Ph.D.
5
Cardiovascular
Physiology
Blood Flow Through the Heart
10
1 Blood enters right atrium from superior
and inferior venae cavae.
2 Blood in right atrium flows through right
Aorta
AV valve into right ventricle.
Left pulmonary
artery
3 Contraction of right ventricle forces
11
5
4 Blood flows through pulmonary valve
9
Superior
vena cava
Right
pulmonary
veins
pulmonary valve open.
5
Pulmonary trunk into pulmonary trunk.
4
6
6
1
7
3
Right
atrium
8
Right AV
(tricuspid) valve
2
Left pulmonary 5 Blood is distributed by right and left
pulmonary arteries to the lungs, where it
veins
Left atrium
Aortic valve
Left ventricle
8 Contraction of left ventricle (simultaneous with
step 3 ) forces aortic valve open.
9 Blood flows through aortic valve into
ascending aorta.
10 Blood in aorta is distributed to every organ in
the body, where it unloads O2 and loads CO2.
11
11 Blood returns to heart via venae cavae.
•
5% (250 ml) of blood
pumped by heart is
pumped to the heart
itself, through the
coronary circulation to
sustain its strenuous
workload
•
Prof. Mark Andrews, Ph.D.
6 Blood returns from lungs via pulmonary
veins to left atrium.
Left AV
7 Blood in left atrium flows through left AV
(bicuspid) valve valve into left ventricle.
Right
ventricle
Inferior
vena cava
unloads CO2 and loads O2.
requires abundant O2
and nutrients
6
Cardiovascular
Physiology
1. Rapid
2. Diastasis
Prof. Mark Andrews, Ph.D.
Cardiac Cycle
1. Maximal
2. Reduced
7
Cardiovascular
Physiology
Wiggers’ Diagram
Carl J. Wiggers
(May 28, 1883 – April 28, 1963)
Prof. Mark Andrews, Ph.D.
8
Cardiovascular
Physiology
•
Phases of Cardiac Cycle (maximally seven)
ventricular filling occurs in three phases:
• (6) rapid ventricular filling - first one-third
• blood enters very quickly and passively as it has been building up in atria via
continuous venous return
• (7) continued filling /diastasis - second one-third
• marked by slower filling as venous return continues, going directly to the
ventricles
• P wave occurs at the end of diastasis, initiating…
• (1) atrial systole - final one-third
• atria contraction, forcing the final portion (10-20%) of cardiac filling (EDV)
• QRS complex occurs at the end of this phase, initiating…
•
(2) isovolumic contraction
•
ventricular ejection occurs in two phases
• (3) initial component is rapid once afterload is overcome
• (4) as ejection continues, the volume ejected is reduced as the
myocardium relaxes
•
(5) isovolumic relaxation as the afterload overcomes ventricular pressure
• the remaining volume is ESV
Prof. Mark Andrews, Ph.D.
9
Cardiovascular
Physiology
•
Ventricular Ejection
ejection of blood begins when the ventricular pressure exceeds arterial pressure
and forces semilunar valves open
•
pressure peaks in left ventricle at about 120 mm Hg and 25 mm Hg in the right
•
blood spurts out of each ventricle rapidly at first – rapid ejection
•
then more slowly under reduced pressure – reduced ejection
•
ventricular ejections last about 200 – 250 msec
•
•
stroke volume (SV) of about 70 mL of blood is ejected of the 130 mL in each
ventricle
•
•
•
corresponds to the plateau phase of the cardiac action potential
ejection fraction of about 54%
as high as 80% in vigorous exercise
end-systolic volume (ESV) – the 60 mL of 130 ml of blood left behind
Prof. Mark Andrews, Ph.D.
10
Cardiovascular
Physiology
Contractile Parameters
•
cardiac cycle - one complete contraction and relaxation of
chambers of the heart
•
stroke volume (SV) – amount ejected by one heart beat
all four
• SV = End diastolic volume (EDV) minus end systolic volume (ESV)
• Ejection fraction (Ej%): SV/EDV
•
cardiac output (Q) – amount of blood ejected per minute
• Q = heart rate x stroke volume
• 4 to 6 L/min at rest
• typically, an RBC leaving the left ventricle will arrive back in about one minute
• vigorous exercise increases Q to 20+ L/min for fit person and can be greater
than 35 L/min for elite athletes
•
cardiac reserve – the difference between a person’s maximum and
resting Q; increases with fitness, and decreases with disease
•
cardiac index – Q per surface area (m2)
•
to keep cardiac output constant as we increase in age, the heart rate
increases as the heart ages and SV decreases.
Prof. Mark Andrews, Ph.D.
11
Cardiovascular
Physiology
Overview of Volume Changes
end-systolic volume (ESV)
-passively added to ventricle
during atrial diastole
-added by atrial systole
total: end-diastolic volume (EDV)
stroke volume (SV) ejected
by ventricular systole
leaves: end-systolic volume (ESV)
60 ml
+60 ml
+10 ml
130 ml
-70 ml
60 ml
both ventricles eject the same amount of blood
Prof. Mark Andrews, Ph.D.
12
Cardiovascular
Physiology
Preload
• three variables govern stroke volume:
• Preload, Contractility, Afterload
• example
• increased preload or contractility causes increases stroke volume
• increased afterload causes decrease stroke volume
• preload – the amount of tension in ventricular myocardium
immediately before it begins to contract (primarily due to
blood volume)
•
•
•
•
increased preload causes increased force of contraction
exercise increases venous return and stretches myocardium
cardiocytes generate more tension during contraction
increased cardiac output matches increased venous return
– Frank-Starling law of heart - SV∝ EDV
• stroke volume is proportional to the end diastolic volume
• ventricles eject as much blood as they receive
• the more they are stretched, the harder they contract
Prof. Mark Andrews, Ph.D.
13
Cardiovascular
Physiology
Prof. Mark Andrews, Ph.D.
Cellular Basis of Starling’s Law of the Heart
14
Cardiovascular
Physiology
Contractility
• contractility refers to how forcefully the myocardium
contracts for a given preload
• positive inotropic agents increase contractility
• hypercalcemia can cause strong, prolonged contractions and even
cardiac arrest in systole
• catecholamines increase calcium levels
• glucagon stimulates cAMP production
• digitalis raises intracellular calcium levels and contraction strength
• negative inotropic agents reduce contractility
• hypocalcemia can cause weak, irregular heartbeat and cardiac
arrest in diastole
• hyperkalemia reduces strength of myocardial action potentials and
the release of Ca2+ into the sarcoplasm
• vagus nerves have effect on atria but too few nerves to ventricles
for a significant inotropic effect
Prof. Mark Andrews, Ph.D.
15
Cardiovascular
Physiology
Afterload
• afterload – the blood pressure in the aorta and pulmonary
trunk immediately distal to the semilunar valves
• opposes the opening of these valves
• limits stroke volume
• hypertension increases afterload and opposes ventricular
ejection
• anything that impedes arterial circulation can also increase
afterload
• lung diseases that restrict pulmonary circulation
• cor pulmonale – right ventricular failure due to obstructed
pulmonary circulation
• in emphysema, chronic bronchitis, and black lung disease
Prof. Mark Andrews, Ph.D.
16
Cardiovascular
Physiology
Prof. Mark Andrews, Ph.D.
Pressure-Volume (Work) Diagram
17
Cardiovascular
Physiology
Prof. Mark Andrews, Ph.D.
18
Cardiovascular
Physiology
Cardiac Conduction System
1 SA node fires.
2
Right atrium
2
1
Sinoatrial node
(pacemaker)
Left
atrium
2
Atrioventricular
node
Atrioventricular
bundle
Purkinje fibers
Prof. Mark Andrews, Ph.D.
Purkinje
fibers
3
Bundle
branches
4
5
Excitation spreads through
atrial myocardium, and
Bachmann’s bundle
3 AV node fires.
4 Excitation spreads down AV
bundle.
5 Purkinje fibers distribute
excitation through
ventricular myocardium.
19
Cardiovascular
Physiology
•
Cardiac Conduction System
coordinates the heartbeat
• composed of an internal pacemaker and specialized myocardial
conduction pathway
• generates and conducts rhythmic electrical signals in the following order:
•
sinoatrial (SA) node - modified myocytes
• in right atrium near base of superior vena cava
• initiates each heartbeat and determines heart rate, ANS modulation
• signal then spreads throughout atria; Bachmann’s bundle to L. atrium
•
atrioventricular (AV) node
• located near the right AV valve at lower end of interatrial septum
• electrical “gateway” to the ventricles; only conduction
• fibrous skeleton, holding valves, acts as an insulator to prevent currents
from getting to the ventricles from any other route
•
atrioventricular (AV) bundle (bundle of His)
• enters into inverventricular septum
• bundle then forks into right (one) and left (two) bundle branches
•
Purkinje fibers
• specialized myocytes which are final connection of conductive fibers to all
other ventricular cells
Prof. Mark Andrews, Ph.D.
20
Cardiovascular
Physiology
•
Nerve Supply to Heart
sympathetic nerves
• fibers terminate in SA and AV nodes, in atrial and ventricular
myocardium, as well as the aorta, pulmonary trunk, and coronary
arteries
• increase heart rate and contraction strength
• POSITIVE CHRONOTROPIC and INOTROPIC EFFECTS
• also dilates coronary arteries to increase myocardial blood flow
•
parasympathetic nerves
• pathway begins with nuclei of the vagus nerves in the medulla
• fibers of right vagus nerve lead to the SA node
• fibers of left vagus nerve lead to the AV node
• stimulation reduces the heart rate; effect on strength is much less
• NEGATIVE CHRONOTROPIC EFFECT
Prof. Mark Andrews, Ph.D.
21
Cardiovascular
Physiology
•
Chronotropic Effects of the ANS
sympathetic postganglionic fibers are adrenergic
• they release norepinephrine
• binds to (β-) adrenergic receptors in the heart
• activates c-AMP second-messenger system in cardiocytes and nodal
cells
• leads to opening of Ca2+ channels in plasma membrane
• increased Ca2+ inflow accelerated depolarization of SA node
• cAMP accelerates the uptake of Ca2+ by the sarcoplasmic reticulum
allowing the cardiocytes to relax more quickly
• by accelerating both contraction and relaxation, norepinephrine and cAMP
increase the heart rate as high as 230 bpm
• diastole becomes too brief for adequate filling
• both stroke volume and cardiac output are reduced
Prof. Mark Andrews, Ph.D.
22
Cardiovascular
Physiology
•
Chronotropic Effects of the ANS
parasympathetic vagus nerves have cholinergic, inhibitory effects on
the SA and AV nodes
• acetylcholine (ACh) binds to cholinergic (muscarinic) receptors
• opens K+ gates in the nodal cells
• as K+ leaves the cells, they become hyperpolarized and fire less
frequently
• heart slows down
• parasympathetics work on the heart faster than sympathetics
• parasympathetics do not use a second messenger system.
•
without influence from the cardiac centers, the heart has a intrinsic
“natural” firing rate of 100 bpm
•
vagal tone – holds down this heart rate to 70 – 80 bpm at rest
• steady background firing rate of the vagus nerves
Prof. Mark Andrews, Ph.D.
23
Cardiovascular
Physiology
Cardiac Rhythm
• cycle of events in heart – special names
• systole – atrial / ventricular contraction
• diastole – atrial / ventricular relaxation
• sinus rhythm = normal heartrate (HR) is triggered by the SA
node
• A regular resting HR = 60 to 100 bpm
• < 60 bpm is bradycardia; > 100 bpm is tachycardia
• adult at rest is usually 70 to 80 bpm (some vagal tone)
• nodal rhythm – from AV node if SA node is damaged, 40 to 50 bpm
• intrinsic ventricular rhythm – if both SA and AV nodes are not
functioning, rate set at 20 to 40 bpm
• this requires pacemaker to sustain life
• ectopic focus - another part of heart fires before the SA node;
visible on EKG
• can be caused by hypoxia, electrolyte imbalance, or caffeine,
nicotine, and other drugs
Prof. Mark Andrews, Ph.D.
24
Cardiovascular
Physiology
SA Node Potentials
•
•
•
•
SA node does not
have a stable resting
membrane potential
(MP)
MP starts at -60 mV
and drifts upward
with a slow inflow
of Na+ without a
compensating
outflow of K+, a
gradual
depolarization is
called pacemaker
potential
Membrane potential (mV)
+10
0
–10
Fast K+
efflux
Fast
Ca2+–Na+
inflow
–20
Action
potential
Threshold
–30
–40
Pacemaker
potential
–50
–60
Slow Na+
inflow (If current)
–70
0
.4
.8
Time (sec)
1.2
1.6
At a threshold of -40 mV, voltage-gated fast Ca2+ and Na+ channels open, with a faster
depolarization occurring and peaking at 0 mV
K+ channels then open and K+ efflux occurs as the cell repolarizes, K+ channels close, and
pacemaker potential starts over
Prof. Mark Andrews, Ph.D.
25
Cardiovascular
Physiology
Electrical Behavior of Myocardium
•
ventricular myocytes have a stable resting potential of -90 mV
•
depolarize only when stimulated
• depolarization phase (very brief)
• stimulus opens voltage regulated Na+ gates, (Na+ rushes in) membrane
depolarizes rapidly
• action potential peaks at +30 mV
• Na+ gates close quickly
• plateau phase lasts 200 to 250 msec, sustains contraction for expulsion of
blood from heart
• Ca2+ channels are slow to close and SR is slow to remove Ca2+ from the cytosol
• repolarization phase - Ca2+ channels close, K+ channels open, rapid
diffusion of K+ out of cell returns it to resting potential
•
has a long absolute refractory period of 250 msec compared to 1 – 2
msec in skeletal muscle
• prevents wave summation and tetanus which would stop the pumping
action of the heart
Prof. Mark Andrews, Ph.D.
26
Cardiovascular
Physiology
Prof. Mark Andrews, Ph.D.
Fast-Type Myocardial Action Potential
27
Cardiovascular
Physiology
Action Potential of a Cardiocyte
3
Membrane potential (mV)
+20
2 Na+ inflow depolarizes the membrane and triggers the opening of still
4
0
3 Na+ channels close when the cell depolarizes, and the
Myocardial
relaxation
voltage peaks at nearly +30 mV.
4 Ca2+ entering through slow Ca2+channels prolongs depolarization of
2
membrane, creating a plateau. Plateau falls
slightly because of some K+ leakage, but most K+ channels remain closed
until end of plateau.
Myocardial
contraction
–60
–80
more Na+ channels, creating a positive feedback cycle and a rapidly
rising membrane voltage.
5
Action
potential
–20
–40
1 Voltage-gated Na+ channels open.
Plateau
Absolute
refractory
period
5 Ca2+ channels close and Ca2+ is transported out of cell. K+ channels
1
open, and rapid K+ outflow returns membrane to its resting
potential.
0
.15
Time (sec)
.30
1) Na+ gates open
2) Rapid depolarization
3) Na+ gates close
4) Slow Ca2+ channels open
5) Ca2+ channels close, K+ channels open (repolarization)
Prof. Mark Andrews, Ph.D.
28
Cardiovascular
Physiology
Normal Electrocardiogram (EKG)
•
P wave
SA node depolarizes and
atria undergo systole
atrial systole begins about
100 msec after SA signal
0.8 second
•
PR interval
Atrial systole until
ventricular sytole starts
Normal range is from
120-210 msec
R
•
R
ventricles depolarize
under 80 msec
specific shape of the
complex is due to
direction of wave of
depolarization and the
shape of the two
ventricles
+1
Millivolts
PQ
segment
ST
segment
T wave
P wave
0
PR
interval
Q
Prof. Mark Andrews, Ph.D.
ST segment ventricular systole
plateau in myocardial
action potential
•
T wave
QRS interval
–1
Atria
contract
•
S
QT
interval
Ventricles
contract
Atria
contract
Ventricles
contract
QRS complex
ventricular
repolarization and
relaxation; shape and
duration differ from QRS
complex
29
Cardiovascular
Physiology
Electrical Activity of Myocardium
Wave of
depolarization
Wave of
repolarization
1 Atria begin depolarizing.
4 Ventricular depolarization complete.
T
P
Prof. Mark Andrews, Ph.D.
2 Atrial depolarization complete.
Ventricular repolarization
5 begins at apex and progresses.
Ventricular depolarization begins
3 at apex and progresses superiorly;
atria repolarize.
6
Ventricular repolarization complete;
heart is ready for the next cycle.
30
Cardiovascular
Physiology
Integration in the Medullary Cardiac Center
§ higher brain centers such as the cerebral cortex, limbic system,
hypothalamus (ANS) affect heart rate (sensory / emotional stimuli)
§ medulla also receives input from muscles, joints, arteries, and other
brainstem nuclei
• proprioceptors in the muscles and joints
• inform cardiac center about changes in activity: HR increases before metabolic
demands rise
• baroreceptors signal cardiac center
• pressure sensors in aorta and internal carotid arteries
• blood pressure decreases, signal rate drops, cardiac center increases heart rate
• if blood pressure increases, signal rate rises, cardiac center decreases heart rate
• chemoreceptors
•
•
•
•
•
in aortic arch, carotid arteries and medulla
sensitive to blood pH, CO2 and O2 levels
more important in respiratory control than cardiac control
hypercapnia and acidosis stimulate the cardiac center to increase heart rate
also respond to hypoxemia – oxygen deficiency in the blood
• usually slows down the heart if hypercapnia / acidosis are not concomitant.
Prof. Mark Andrews, Ph.D.
31
Cardiovascular
Physiology
Properties of Blood
• viscosity - resistance of a fluid to flow, resulting from the
cohesion of its particles
– whole blood 4.5 - 5.5 times as viscous as water
– plasma is 2.0 times as viscous as water
• important concept in circulatory function
– important parameter determining turbulent flow
– best understood as “stickiness”
• Oncotic pressure of blood - the total molarity of proteins
dissolved in plasma, that cannot pass through the capillary
walls
–
–
–
–
affect transit of fluid across of capillary walls by draws water to them
if too high, there will be too much fluid, increasing the blood pressure
if too low, fluid leaks into tissues, edema occurs and blood pressure drops
optimum oncotic pressure is achieved by regulation of protein production in
the liver.
– liver damage will greatly affect oncotic pressure
– a component of Starling Forces
Prof. Mark Andrews, Ph.D.
32
Cardiovascular
Physiology
Starling Forces
Net
filtration
pressure:
13 out
Forces (mm Hg)
33 out
Net
reabsorption
pressure:
7 in
13 out
20 in
Capillary
20 in
Blood flow
Venule
Arteriole
Arterial end
•
fluid filters out of the capillary and osmotically
reenters at the venous end, delivering
materials to the cell and removes metabolic
wastes
•
opposing forces
• hydrostatic pressures drives fluid away
• high BP on arterial end of capillary
• colloid oncotic pressure (COP) draws
fluid towards the protein (20 mmHg)
capillaries reabsorb 90% of the fluid they filter
other 10% is absorbed by the lymphatic
system and returned to the blood
•
•
Prof. Mark Andrews, Ph.D.
Venous end
33