Phys Ch 20
Cardiac Output, Venous Return, and Their Regulation
 Cardiac output – quantity of blood pumped into aorta each minute by heart; used to measure blood flow to
tissues
 Venous return – quantity of blood flowing from veins into right atrium each minute; must be equal to cardiac
output except for the few heartbeats when that blood is in the heart or lungs
Normal Values for Cardiac Output at Rest
 Cardiac output directly affected by
o Basic level of body metabolism
o Whether or not person is exercising
o Person’s age (with increasing age, body activity and mass of some tissues like skeletal muscle diminish)
o Size of body
 For young, healthy men, resting cardiac output averages 5.6 L/min – for women ,the value is about 4.9 L/min –
often estimated everyone at 5 L/min
 Cardiac index – cardiac output per square meter of body surface area
o Cardiac index rises rapidly throughout childhood and peaks at 10 years of age (4 L/min/m2) then goes
through a slow hyperbolic decline
Control of Cardiac Output by Venous Return – Role of Frank-Starling Mechanism of Heart
 Cardiac output is controlled by venous return, so ultimately, cardiac output is controlled by factors of peripheral
circulation
 Frank-Starling law of the heart – when increased quantities of blood flow into heart, increased blood stretches
walls of the heart chambers, and as a result of this stretch, cardiac muscle contracts with increased force, which
empties the extra blood from systemic circulation
o Stretching of heart causes heart to pump faster (stretch of sinus node increases heart rate as much as
10-15%)
o Bainbridge reflex – caused by stretched right atrium; passes first to vasomotor center of brain then back
to heart by way of sympathetic nerves and vagus – increases heart rate
 Under most normal not stressful conditions, cardiac output controlled almost entirely by peripheral factors that
determine venous return
o If returning blood becomes more than heart can pump, heart becomes limiting factor that determines
cardiac output
 In most tissues, blood flow increases mainly in proportion to each tissue’s metabolism
o Metabolism increases when oxygen consumption of tissues increases
 Long-term cardiac output level varies reciprocally with changes in total peripheral resistance as long as arterial
pressure is unchanged
o
o
When total peripheral resistance increases above normal, cardiac output falls
Understood by Ohm’s law (cardiac output = arterial pressure/total peripheral resistance)
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Normal heart can pump a venous return up to 2.5x normal amount before heart becomes limiting factor in
control of cardiac output
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Heart can become hypereffective through nervous stimulation or hypertrophy of heart muscle
Combination of sympathetic stimulation and parasympathetic inhibition increases pumping effectiveness of
heart because it greatly increases heart rate and it increases strength of heart contraction – both work together
to increase cardiac output curve to almost twice normal plateau (blue line in above figure)
o Long-term increased workload causes hypertrophy
o Marathon runners have combined hypertrophy and nervous excitation that increases their cardiac
output curve to 2.5x normal (this is what allows them to run that long)
Any factor that decreases heart’s ability to pump also causes hypoeffectivity
o Increased arterial pressure against which heart must pump (i.e., hypertension)
o Inhibition of nervous excitation of heart
o Pathological factors that cause abnormal heart rhythm or rate
o Coronary artery blockage
o Valvular heart disease
o Congenital heart disease
o Myocarditis (inflammation of heart muscle)
o Cardiac hypoxia
Maintenance of normal arterial pressure by nervous reflexes is essential to achieve high cardiac outputs when
peripheral tissues dilate their vessels to increase venous return
During exercise, intense increase in metabolism in active skeletal muscles acts directly on muscle arterioles to
relax them and allow adequate oxygen and other nutrients needed to sustain muscle contraction
o Greatly decreases total peripheral resistance, which would normally decrease arterial pressure as well
o Motor signals also carry signals to autonomic nervous centers of brain to excite circulatory activity,
causing large vein constriction, increased heart rate, and increased contractility of heart – increase
arterial pressure above normal, which forces still more blood flow through active muscles (increases
cardiac output)
o When local tissue blood vessels dilate and thereby increase venous return and cardiac output above
normal, nervous system prevents arterial pressure from falling to disastrously low levels
Pathologies that cause cardiac outputs higher than normal all result from chronically reduced total peripheral
resistance (none from excessive excitation of the heart)
o Beriberi – disease caused by insufficient quantity of thiamine (vitamin B1) – causes diminished ability of
tissues to use some cellular nutrients, and local tissue blood flow mechanisms cause marked
compensatory peripheral vasodilation
 Long-term levels of venous return and cardiac output increase to twice normal while peripheral
resistance decreases to as little as ½ normal
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o
Arteriovenous fistula (shunt) – between major artery and major vein; tremendous amounts of blood
flow directly from artery to vein, decreasing total peripheral resistance and increasing venous return and
cardiac output
o Hyperthyroidism – metabolism of most tissues of body becomes greatly increased
 Oxygen usage increases, vasodilator products released from tissues
 Total peripheral resistance decreases markedly because of local tissue blood flow control
reactions throughout body
o Anemia – reduced viscosity of blood, resulting from decreased concentration of RBCs, and diminished
delivery of oxygen to tissues, which causes local vasodilation, both greatly decrease total peripheral
resistance, and cardiac output greatly increases
 Conditions that cause abnormally low cardiac output either cause pumping effectiveness of heart to fall too low
or cause venous return to fall too low
o Whenever heart becomes severely damaged, regardless of cause, its limited level of pumping may fall
below that needed for adequate blood flow to tissues (severe coronary blood vessel blockage and
subsequent myocardial infarction, severe valvular heart disease, myocarditis, cardiac tamponade, or
cardiac metabolic derangements)
o When cardiac output falls so low that tissues throughout body begin to suffer nutritional deficiency,
cardiac shock occurs
 Anything that interferes with venous return can lead to decreased cardiac output (and can lead to circulatory
shock [shock caused by cardiac output value lower than level required for adequate nutrition of tissues])
o Decreased blood volume – most common noncardiac peripheral factor that leads to decreased cardiac
output; results most often from hemorrhage
o Acute venous dilation – results most often when SNS suddenly becomes inactive; fainting results from
sudden loss of SNS activity, which causes peripheral capacitative vessels to dilate markedly – decreases
filling pressure of vascular system because blood volume can no longer create adequate pressure in
flaccid peripheral blood vessels, so blood pools in vessels and does not return to heart
o Obstruction of large veins – blood cannot get back to heart, so won’t contribute to cardiac output
o Decreased tissue mass, especially decreased skeletal muscle mass (as happens with age or periods of
inactivity) – decreases total oxygen consumption and blood flow needs of muscles
o Decreased metabolic rate of tissues – decreased need of oxygen and nutrients reduces blood flow to
tissues – can also be caused by hypothyroidism
Measuring Cardiac Output Regulation
 Pumping ability of heart represented by cardiac output curves
 Peripheral factors that affect flow of blood from veins into heart represented by venous return curves
 Normal external cardiac pressure is equal to normal intrapleural pressure (pressure in chest cavity), which is -4
mm Hg – increasing intrapleural pressure shifts cardiac output curve to right by same amount; shift occurs
because to fill cardiac chambers with blood requires extra effort on right atrial pressure to overcome increased
pressure outside heart
o Factors that can alter external pressure on heart and thereby shift cardiac output curve
 Cyclical changes of intrapleural pressure during respiration (about ±2 mm Hg during normal
breathing, but can be as much as ±50 mm Hg during strenuous breathing)
 Breathing against negative pressure (shifts curve to left)
 Positive pressure breathing shifts curve to right
 Opening thoracic cage – increases intrapleural pressure to 0 mm Hg
 Cardiac tamponade – causes increase in external cardiac pressure and shifting of curve to right;
shifts upper parts of curves farther to right than lower parts because tamponade pressure rises
to higher values as chambers of heart fill to increased volumes during high cardiac output
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3 principle factors affect venous return to heart form systemic circulation
o Right atrial pressure – exerts backward force on veins to impede flow of blood from veins into right
atrium
o Mean systemic filling pressure – forces systemic blood toward heart
o Resistance to blood flow between peripheral vessels and right atrium
o All of above can be expressed by venous return curve
Venous return curve relates venous return to right atrial pressure
Normal venous return curve (in absence of
nervous circulatory reflexes)
o
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When heart pumping capability becomes diminished and causes right atrial pressure to rise, backward
force of rising atrial pressure on veins of systemic circulation decreases venous return of blood to heart
o If right atrial pressure rises, venous return drops because systemic circulation is essentially a distensible
bag, so any increase in back pressure causes blood to dam up in the “bag” instead of returning to heart –
at the same time, pumping by heart approaches zero because of decreasing venous return
 Both arterial and venous pressures come to equilibrium when all flow in systemic circulation
ceases (this pressure is the mean systemic filling pressure (Psf)
o Plateau caused by collapse of veins entering chest – negative pressure in right atrium sucks walls of
veins together where they enter chest, which prevents any additional flow of blood from peripheral
veins
Mean circulatory filling pressure is the pressure that every place in circulation would come to equilibrium at
should heart fail to pump
o The greater the volume of blood in circulation, the greater the mean circulatory filling pressure
When circulatory filling pressure is 0 mm Hg,
this is the unstressed volume of the vessels
Note steepness of curves. Even slight
changes in blood volume or in capacity of
system caused by various levels of SNS
activity can have large effects on mean
circulatory filling pressure.
o
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Strong SNS stimulation constricts all systemic blood vessels as well as larger pulmonary blood vessels,
and even chambers of the heart; therefore, capacity of system decreases so that at each level of blood
volume, mean circulatory filling pressure is increased – maximal SNS stimulation increases mean
circulatory filling pressure of about 2.5x its normal value (raises to about 17 mm Hg)
Mean systemic pressure (Psf) – pressure measured everywhere in systemic circulation after blood flow has been
stopped by clamping large blood vessels at heart, so pressures in systemic circulation can be measured
independently from those in pulmonary circulation – important pressure for determining venous return
o Almost always nearly equal to mean circulatory filling pressure because pulmonary circulation has less
than 1/8 as much capacitance as systemic circulation and only about 1/10 as much blood volume
o
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The greater the Psf, the more venous return curve shifts upward and to the right (the greater the system
is filled, the easier it is for blood to flow into the heart)
When right atrial pressure rises to equal Psf, there is no longer any pressure difference between peripheral
vessels and right atrium, so there can no longer by any blood flow from any peripheral vessels back to right
atrium
When right atrial pressure falls lower than Psf, flow to heart increases proportionately (the greater the
difference between Psf and right atrial pressure, the greater venous return)
Resistance to venous return – mostly in veins, though some occurs in arterioles and small arteries
o When resistance in veins increases, blood begins to be dammed up, mainly in veins themselves – venous
pressure rises very little because veins are highly distensible, so resistance not overcome
o When arteriolar and small artery resistances increase, blood accumulates in arteries, which have
capacitance 1/30 as great as that of veins, so slight accumulation of blood in arteries raises pressure
greatly – this overcomes much of increased resistance
o About 2/3 of resistance to venous return determined by venous resistance and 1/3 by arteriolar and
small artery resistance
o VR = (Psf-PRA)/RVR where VR is venous return, Psf is mean systemic filling pressure, PRA is right atrial
pressure, and RVR is resistance to venous return
o
Decrease in resistance to venous return decreases resistance and rotates curve upward
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When right atrial pressure rises to equal mean systemic filling pressure, venous return becomes zero at all levels
of resistance to venous return because when there is no pressure gradient to make blood flow, it makes no
difference what resistance is in circulation
Highest level to which right atrial pressure can rise, regardless of level of heart failure, is equal to Psf
Calculating cardiac output by graphing
cardiac output curve (red) and momentary
state of flow from systemic circulation into
heart (venous return curve (blue); cardiac
output and right atrial pressure are point A.
Transfusion of blood equal to 20% of blood
volume causes venous return curve to
become dashed curve (cardiac output and
right atrial pressure shift to point B)
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Point A in graph above is equilibrium point
Shift to point B – immediately on infusing large quantity of extra blood, increased filling of system causes Psf to
increase, which shifts venous return curve to right; at same time, increased blood volume distends blood
vessels, thus reducing their resistance and thus resistance of venous return, which rotates curve upward
o Greatly increased cardiac output caused by increased blood volume lasts for only a few minutes because
 Increased cardiac output increases capillary pressure so that fluid begins to transude out of
capillaries into tissues, thus reducing blood volume
 Increased pressure in veins causes veins to continue distending gradually by stress-relaxation,
especially causing venous blood reservoirs, such as liver and spleen, to distend, thus reducing
mean systemic pressure
 Excess blood flow through peripheral tissues causes autoregulatory increase in peripheral
vascular resistance, thus increasing resistance to venous return
o All of above cause Psf to return back toward normal and resistance vessels of systemic circulation
constrict, returning cardiac output to normal in 10-40 minutes
SNS stimulation increases Psf because of contraction of peripheral vessels, especially veins, increasing resistance
to venous return
o SNS increases cardiac output, but right atrial pressure hardly changes
o
o
Different degrees of SNS stimulation can increase cardiac output progressively for short periods of time
until other compensatory effects occur within seconds or minutes
Total spinal anesthesia (hexmethonium) blocks transmission of nerve signals through autonomic ganglia
(blocking SNS)
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Circulatory changes that occur after opening a large arteriovenous fistula (connecting large artery to large vein)
Red curves represent normal conditions. Black lines show
immediately after opening large fistula. Lavender lines represent
effects about 1 minute after opening fistula. Green lines are after
several weeks.
o
Immediately after opening large fistula, principal effects are sudden rotation of venous return curve
upward caused by large decrease in resistance to venous return and slight increase in level of cardiac
output curve because opening fistula decreases peripheral resistance and allows acute fall in arterial
pressure against which heart can pump more easily – net result is increase in cardiac output and
increase in right atrial pressure
o About 1 minute after opening fistula, SNS reflexes have restored arterial pressure almost to normal and
caused increase in Psf (because of constriction of all veins and arteries), shifting venous return curve to
right, and further elevation of cardiac output curve because of SNS excitation of heart
o After several weeks, blood volume increases because slight reduction in arterial pressure and SNS
stimulation have both reduced kidney output of urine
 Psf has risen again, shifting venous return curve to the right yet again
 Prolonged increased workload on heart has caused slight hypertrophy of heart muscle, raising
level of cardiac output
Methods for Measuring Cardiac Output
 Usually measured by indirect methods (oxygen Fick method and indicator dilution method)
 Cardiac output can be estimated by echocardiography (ultrasound waves to image heart) – stroke volume
calculated from velocity of blood flowing into aorta and aorta cross-sectional area determined from aorta
diameter measured by ultrasound – cardiac output is stroke volume times heart rate
 Blood flow rises through cardiac cycle to peak at systole, and at end of systole reverses for fraction of a second,
which causes aortic valve to close and flow to return to zero
 Fick principle – cardiac output = (O2 absorbed by lungs (mL/min))/(arteriovenous O2 difference (mL/L of blood))
o Using this to measure cardiac output – mixed venous blood obtained through catheter inserted up
brachial vein of forearm, through subclavian, down to right atrium and into right ventricle or pulmonary
artery; systemic arterial blood is obtained from any systemic artery in body; rate of oxygen absorption
by lungs measured by rate of disappearance of oxygen from respired air with oxygen meter
 Indicator dilution method – small amount of indicator (dye) injected into large systemic vein or, preferably, right
atrium; dye passes through circulation to systemic arterial system; concentration of dye recorded as dye passes
through one of peripheral arteries, giving curve (below)
Dye concentrations plateau because by this point, some of dye has already
gone through circulation and is returning (hence dashed line is extrapolated
to find zero point)
Mean concentration of dye in arterial blood calculated for duration of curve
(measuring area under entire initial and extrapolated curve and averaging
concentration of dye for duration of curve – shaded rectangle is average
concentration of dye)
Thus cardiac output = (mg of dye injected * 60)/(average concentration of dye
in each mL of blood for duration of curve * duration of curve in seconds)