CARDIAC OUTPUT

12-Jul-23 Physiology of the heart 1

• Cardiac Output is the quantity of blood that flows through the
circulatory system per minute
• It responsible for transporting substances to and from the
tissues.
• Maintaining and regulating cardiac output, which is usually
proportional to the tissues' need for oxygen and other nutrients,
is one of the circulatory system's most intricate functions.
• CO is an essential part of the circulatory function

12-Jul-23 Physiology of the heart 2

 Cardiac output
Cardiac output is the quantity of blood pumped out of each ventricle
per minute by the heart. It can be expressed in three ways.
• Stroke volume: the amount of blood pumped out of each ventricle
per beat and is about 70mL in a resting man of average size.
• Minute volume or Cardiac Output: it is the amount blood pumped
out of each ventricle in one minute.
• It is the product of stroke volume x heart rate.
• Cardiac index: it is the CO per square meter of body surface area. It
averages about 3L/min/m2 for normal human being weighing 70kg
with body surface area of about 1.7m2.
 Cardiac output
• Heart rate: is the beats per minute and averages
75beats/min in an adult at rest.

• CO = HR x SV. Therefore,

75 beats 70 mL
• CO = min
x beat

5250 mL 5.25 L
= min = min
 Cardiac output

• It is typically about 5,250 milliliters (or 5.25 liters) per minute

(which is about equal to total blood volume; so, each
ventricle pumps the equivalent of total blood volume each
minute under resting conditions) BUT maximum may be as
high as 25 - 35 liters per minute.
• For young healthy men, resting CO averages about 5.6 L/min.
• For women, this value is about 4.9 L/min.
• At rest the heart pumps only 4 to 6 liters of blood per minute.
• In times of severe exercise, the amount the heart pumps may go up
by three to five times this amount.
• The amount pumped out by the heart per minute is controlled by
• (1) An intrinsic cardiac regulation of pumping in response to changes
in volume of blood flowing into the heart and
• (2) Regulation of the heart rate and strength of contraction of the
heart by the autonomic nervous system

12-Jul-23 Physiology of the heart 6

• CO = SV x HR

12-Jul-23 Physiology of the heart 8

HEART RATE

• Intrinsic Control
• The heart rate is established by the SA node
• Extrinsic Control.
• The SAN and AV nodes are innervated by the autonomic nervous
system (ANS).
• The ANS innervation affects the membrane's permeability to Ca+2,
Na+ to make depolarization more or less difficult.

12-Jul-23 Physiology of the heart 9

Parasympathetic Division

• Innervation via the Vagus Nerve which innervates both the SA & AV nodes.
• Responsible for a decrease in HR by slowing the depolarization to
threshold.
• There is no significant ventricle vagal innervation.
• Decrease in velocity of transmision of impulses from SAN to AV Node ((-ve
dromotropic effect)
• Also increases AV nodal delay thus prolonging the transmission of impulses
to the ventricles making the delay even longer than the usual AV nodal
delay.
• The neurotransmitter is acetylcholine via muscarinic receptors
12-Jul-23 Physiology of the heart 10
Sympathetic Division

• The SNS innervates the atria (including SA & AV nodes), and richly
innervate the ventricles as well.
• Results in increase in the rate of depolarization to threshold in the SA
node and reduces AV nodal delay.
• It also causes an increase in velocity of transmission of impulses from
SAN to AV node (+ve dromotropic effect)
• The neurotransmitter involved here is norepinephrine via β1
receptors

12-Jul-23 Physiology of the heart 11

Hormones

• Hormones can affect heart rate as well.

• Epinephrine released by the adrenal medulla affects the heart rate
just as the sympathetic division.
• Emotional states affect the ANS & hormone release as well.
• Other hormones such as thyroid hormones will also increase the
heart rate as well

12-Jul-23 Physiology of the heart 12

HEART RATE

• Intrinsic Control
• The heart rate is established by the SA node
• Extrinsic Control.
• The SAN and AV nodes are innervated by the autonomic nervous
system (ANS).
• The ANS innervation affects the membrane's permeability to Ca+2,
Na+ to make depolarization more or less difficult.

12-Jul-23 Physiology of the heart 13

Ionic balance
• An increase in the influx of Ca & Na+ increases the rate of
depolarization of the SA node thus resulting in increased HR.
• An increase in the efflux of K+ and a decrease in the influx of Ca
hyperpolarizes the cell with resultant decrease in heart rate

12-Jul-23 Physiology of the heart 14

Drugs

• Sympathomimetics
• Drugs mimicking the effect of SNS stimulation will result in effects similar to
sympathetic division – increase in HR
• Parasympathomimetics
• Drugs mimicking the effect of PSNS will result in effects similar to
parasympathetic stimulation – decrease in HR
• Sympathetic and Parasympathetic blocking agents
• Reverse the effects of sympathetic and parasympathetic respectively

12-Jul-23 Physiology of the heart 15

Physical Factors:

• • Age
• Heart rate decreases over lifetime
• • Gender: Heart rate is normally higher in females as compared to
males
• • Exercise
• HR rate increases during exercise. Conditioned athletes have lower
resting HR and this is because they have a more efficient hear

12-Jul-23 Physiology of the heart 16

• Body temperature
• Diffusion and enzyme activity is slower at lower temperatures with resultant decrease in
heart rate while the reverse is the case.
• FACTORS AFFECTING HR
• i. ANS: PSNS- Decrease in SAN discharge rate, Decrease in conduction velocity from SAN-
AV node, increase in AV delay
• SNS: Increase in SAN discharge, Increase in conduction velocity, increased
conduction of impulse through the AV node
• Ii. Hormones; Epinephrine from adrenal medulla, thyroxine; both increase HR
• Iii. Age; HR decreases over a lifetime
• Iii; Exercise & Fitness: As one exercises, HR increases, however, for a more fir person, the
HR increase will be lower since he will have a more effective heart
• Gender; HR higher in females than males

12-Jul-23 Physiology of the heart 17

 Factors affecting Stroke Volume

1. Venous return: amount of blood coming back to the

heart(determined by EDV)
-respiratory & skeletal muscle pump
-Gravity
-Venous pressure
-SNS
2. Force of contraction
3. Heart rate
4. Peripheral resistance
12-Jul-23 Physiology of the heart 18
12-Jul-23 Physiology of the heart 19
 Stroke volume
• Stoke volume is the volume of blood pumped out of
each ventricle per beat or contraction.
• It correlates with the force of ventricular contraction.
• As the SV increases cardiac output also increases.
SV depends upon
1. End diastolic volume: The amount of blood collected
in a ventricle during diastole (relaxation) and
2. End systolic volume: the volume of blood remaining in the
ventricle after it has contracted.
120 mL 50mL 70mL
• SV = EDV – ESV = − =
beat beat beat
• The SV for each ventricle are generally equal, both being
approximately 70mL in a healthy 70kg man.
• Men on average have higher SV than women, due to larger
size of their heart.
12-Jul-23 Physiology of the heart 22
 Regulation of stroke volume
Regulated by three variables
• Preload: EDV, all the extent of stretch of the ventricular muscle
fibers
• Contractility (force of contraction of the ventricular muscles &
• Afterload- the force to which the ventricles have to pump
against- represented by the total peripheral resistance ie-
degree of contraction of the arterioles (resistance vessels)
 Regulation of stroke volume

• Preload is the degree of stretch of the heart muscle

before it contracts.
• Within limits, the more the heart fills with blood
during diastole, the greater the force of contraction
during systole. (Frank-Starling law of the heart).
• Thus, preload is proportional to the EDV; the greater
the EDV, the more forceful the next contraction
FRANK STARLING LAW

• Force of ventricular contraction is directly proportional to initial

length of muscle fibers.
• Pre Load is directly proportional to End Diastolic Volume.
• (End Diastolic Volume is the amount of blood remaining in ventricles
at the end of diastole).
• Greater is preload; more is length of muscle fibers.
• EDV is increased by greater venous return.
• Therefore the more is pre load, the more is force of myocardial
contraction.

12-Jul-23 Physiology of the heart 25

• Starling's Law describes the relationship between end-diastolic
volume and stroke volume. It states that the –normal heart- heart will
pump out whatever volume is delivered to it.
• If the end-diastolic volume doubles then stroke volume will double.

12-Jul-23 Physiology of the heart 26

Frank-Starling Law Of The Heart

• The heart normally pumps the blood returned to it

• Therefore, the more blood that is returned to the heart (venous
return) the higher the EDV and therefore the higher the stroke
volume.
• The extent of cardiac filling is referred to as the “preload
• It is called the preload, because it is the work load imposed on the
heart before contraction even begins

12-Jul-23 Physiology of the heart 27

Frank-Starling Law
• What goes into the heart comes out.
• Increased heart volume stretches muscles and causes stronger
contraction.
• Stretch increases heart rate as well.
• Direct effect on sino-atrial node

12-Jul-23 Physiology of the heart 28

 Factors affecting EDV (Preload)
Two key factors determine EDV:
1. The duration of ventricular diastole and,
• When the heart rate increases the duration of diastole is shorter, less filling
means a smaller EDV, and the ventricles may contract before they
adequately filled.- this is not a worry within the normal physiological limits
2. Venous return
• When venous return increases, there is greater volume of blood flow into
the ventricles and EDV increases
• VR is the quantity of blood flowing from the veins in to the right atrium per
minute- remember the veins are referred to as capacitance vessels and
store most of the blood
 Venous return
• It is the quantity of blood flowing from veins into atrium per minute.
• CO is directly proportional to VR, provided the other factors remain
constant.
• Venous return depends on
i. Respiratory pump
ii. Muscle pump
iii. Gravity
iv. Venous pressure
v. Sympathetic tone.
 Respiratory pump
• RP is the respiratory activity that helps the return of blood to the heart
during inspiration.
• Increase in diameter of inferior vena cava, results in increased venous
return
• Descent of diaphragm increases intra-abdominal pressure, compresses
abdominal veins ,pushes blood towards the heart and increases VR
• As such, in case of increase in activity such as exercise, there is normally
an increase in respiratory rate hence increase in respiratory pump-
resultant increase in VR
• As such, in case of increased activity, there is increased CO independent
of any increase in SNS activity
 Muscle pump
• MP is the muscular activity that helps in return of blood to heart.
• during muscular activities, the veins are compressed .
• Due to the presence of valves in veins, during compression the
blood is moved to the heart.
• Increases in muscular activity increases VR.
• As such, in case of increase in activity such as exercise, there is
increased activity in muscle pump with resultant increase in VR
hence increase in CO
• As such, in case of increased activity, there is increased CO
independent of any increase in SNS activity
 Gravity
• Gravitational force reduces the venous return.
• When a person stands for a long period, gravity causes
pooling of blood in the legs, termed venous pooling.
• This results in decrease of blood retuning to the heart.
 Venous pressure
• The pressure gradient at every part of venous tree helps as a driving force for
venous return
• Pressure in the venules 12 to 18mm Hg.
• Pressure in the inferior and superior vena cava falls to about 5.5mm Hg
• Pressure at junction of vena cava & right atrium 4.6mm Hg
• Pressure in right atrium is still low and alters during cardiac action. It falls to zero
during atrial diastole.
• In case of heat failure, blood may dam in the left ventricle, which causes
pulmonary edema, which will increase venous pressure in pulmonary vessels,
resultant increase in right atrial pressure and overall decrease in venous return
 Sympathetic tone
• Sympathetic or vasomotor tone aids VR by causing constriction of
veins.
• Veins are capacitance vessels.
• In time of need, there will be increased SNS activity leading to
venoconstriction
• This translocates the stored blood into circulation with resultant
increase in VR, hence increased EDV with resultant increase in SV &
CO
• This explains the increase in CO from 5l at rest to more than 25l
during strenuous exercise
 Regulation of stroke volume

• Contractility is the forcefulness of contraction of

individual ventricular muscle fibers.
• Substances that increase contractility are positive
inotropic agents
• Those that decrease contractility are negative
inotropic agents.
• The SV increase when a positive inotropic substance is
present.
 Regulation of stroke volume
• +ve inotropic agents often promote Ca2+ inflow during cardiac action
potentials, which strengthens the force of the next contraction.
• Increased sympathetic stimulation increases contractility of the heart,
• Hormones such as epinephrine and norepinephrine, increase Ca2+ .
Thyroid hormones also increase contractility
• Will cause decrease in ESV
• In contrast, inhibition of sympathetic stimulation, acidosis and
increased K+ have –ve inotropic effects
 Regulation of stroke volume
• Afterload is the pressure that must be exceeded before ejection of blood
from the ventricles can occur.
• Ejection of blood from heart begins when pressure in the right ventricle
exceeds the pressure in the pulmonary trunk (about 20mmHg), and
• When the pressure in the left ventricle exceeds the pressure in the aorta
(about 80mmHg).
• Increase in afterload causes a decrease in SV, so that more blood
remains in the ventricles at the end of systole
• Afterload is a measure of the peripheral resistance and the higher it is ,
the less the SV and the less the CO
 Factors regulating CO

CO is effected by four factors

• Venous return
• Force of contraction
• Heart rate
• Peripheral resistance
 Force of contraction
• This a function of 2 factors
• 1. Increased preload which according to sterling law causes
increased force of contraction
• According to Frank-Starling law, force of contraction of a
normal heart is directly proportional to the initial length of
muscle fibers, before the onset of contraction
• 2. SNS stimulation which causes increased force of
contraction
Frank-Starling Law Of The Heart

• The heart normally pumps the blood returned to it

• Therefore, the more blood that is returned to the heart (venous
return) the higher the EDV and therefore the higher the stroke
volume.
• The extent of cardiac filling is referred to as the “preload
• It is called the preload, because it is the work load imposed on the
heart before contraction even begins

12-Jul-23 Physiology of the heart 44

Preload

12-Jul-23 Physiology of the heart 45

Increased Sympathetic Stimulation
Increased sympathetic stimulation (due to fright, anger, etc.)
increases the heart rate.
It also increases stroke volume by increasing contractility,
which results in more complete ejection of blood from the
heart (lower ESV).

12-Jul-23 Physiology of the heart 46

Increased Venous Return
• Cardiac muscle fibers are stretched by increased blood
volume returning to the heart (increased venous
return and EDV).
• Increased stretch results in greater force of
contraction, which increases stroke volume.

12-Jul-23 Physiology of the heart 47

Slow or Fast Heart Rate
• Slow heart rate allows for more time for ventricular
filling, increasing EDV and therefore stroke volume.
• Extremely rapid heart rate results in low venous
return and therefore decreased stroke volume.

12-Jul-23 Physiology of the heart 48

Exercise
Exercise activates the sympathetic nervous
system, increasing heart rate, contractility, and
stroke volume.
Both the higher heart rate and squeezing action
of skeletal muscles on veins increase venous
return, contributing to increased stroke volume.

12-Jul-23 Physiology of the heart 49

Sudden Drop in Blood Pressure
A sudden drop in blood pressure (as in case
following hemorrhage) results in low venous
return and therefore decreased stroke volume.
However heart rate increased due to sympathetic
activity, and normal cardiac output is maintained.

12-Jul-23 Physiology of the heart 50

Afterload
 Afterload is the tension (or the arterial pressure) against which
the ventricle must contract.
 If arterial pressure increases, afterload also increases.
 Afterload for the left ventricle is determined by aortic pressure,
afterload for the right ventricle is determined by pulmonary
artery pressure

12-Jul-23 Physiology of the heart 51

• Afterload is a measure of the pressure that must be generated by
the ventricles to force the semilunar valves open.
• The greater the afterload, the smaller the stroke volume.
• Arteriosclerosis (narrowing of the arteries) and high blood
pressure increase afterload and reduce stroke volume.
• Afterload is basically the pressure against which the left
ventricle has to push the blood from it to the aorta, so if that
pressure decreases, it'll be easier for the blood to be pushed
thru’ it, which is the stroke volume

12-Jul-23 Physiology of the heart 52

• If output resistance is high, a standard contraction will force out less
blood than normal.
• Starling's law remedies this problem.
• Higher output resistance overwhelms one beat forcing some blood to
remain in the ventricle; thus, for the next beat the ventricle will be
extra full ie, a higher EDV, so next beat will be more forceful.
 Cardiac Output Regulation

Figure 11.7
12-Jul-23 Physiology of the heart
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Slide 54
 Determinants of Cardiac Output (CO)

Contractility

Preload Stroke Afterload

Volume
Heart Rate

Cardiac Output

12-Jul-23 Physiology of the heart 55

• Cardiac Output is a function of the interplay of multiple physiologic
parameters.
• Stroke volume influenced in a predictable order:
• 1. Preload first influences contractility.
• 2. The combined effect of preload and contractility then influences
the afterload response.
• 3. Only after the stroke volume is established does the heart rate
respond to adjust the final cardiac output.

12-Jul-23 Physiology of the heart 56

 Regulators of the Heart:
Factors Influencing Stroke Volume

Figure 14-31: Factors that affect cardiac output

12-Jul-23 Physiology of the heart 57
Causes of abnormal cardiac output

• High cardiac output is almost always caused by

• reduced total peripheral resistance.
• Low cardiac output is caused by
(1) decreased ability
• of the heart to pump (severe infarction, valvular disease,
• cardiac damage, cardiac metabolic derangements); and
(2) decreased venous return (decreased blood volume,
• acute venous dilatation, obstruction of large veins).
• Circulatory shock – decrease of cardiac output below an adequate level
12-Jul-23 Physiology of the heart 58
• In contrast, high cardiac output satisfies periods of high energy
demand.
• Rate of flow to tissues depends on tissue needs (i.e. it depends on
Total Peripheral Resistance).
• Therefore, cardiac output is proportional to the energy requirements
of the tissues.

12-Jul-23 Physiology of the heart 59

 Disease States Lowering Total Peripheral
Resistance

• Beriberi: insufficient thiamine – tissues starve because they

cannot use nutrients.
• Hyperthyroidism: Reduced resistance caused by increased
metabolism
• Anemia (lack of RBCs): effects viscosity and transport of O2 to
the tissues.

12-Jul-23 Physiology of the heart 60

Disease States Lowering Cardiac Output
• Heart attack, valvular disease, myocarditis, cardiac tamponade, shock.
• Shock: Nutritional deficiency of tissues.
• Decreased venous return caused by:
• Reduced blood volume
• Venous dilitation (increased circulatory volume)
• Venous obstruction

12-Jul-23 Physiology of the heart 61

 Physiological variations of CO
• Age: CO is more in adults than in children because
blood volume is more.
• Gender: CO is more in males than in females.
• Altitude: CO increases at high altitude places .
• Pregnancy: CO increases during pregnancy
• Exercise: CO increases during exercise.
• Emotion: CO increases during emotional expressions.
 Relationship with BP
• As CO is made up of HR and SV. At rest these are
relatively constant.
• With exercise the heart beats faster. More blood is
pumped out with each beat contributing to a rise in
BP.
• Changes in the volume of blood within the
cardiovascular system will also affect BP.
 Relationship with BP
• If a person was severely dehydrated or lost a large
quantity of blood, there would be less blood for the
heart to pump, thereby reducing the CO and BP.
• For a typical, fit young person, the CO might go up to
about 20L/min at the peak of exercise.
• For a world class athlete in an edurance sport, the
maximum CO might be around 35L/m.
 Regulation of CO
• This means maintaining a constant CO under normal
conditions and adjusting the CO as per the
physiological demands.

• It has to be regulated to have an optimum

cardiovascular efficiency.
 Mechanism of regulation
1. By venous return

• FoC of a muscle fiber is proportional to its initial

length, known as the Starling’s law of muscle
contraction.
2. By nervous system
• Autonomic nervous system takes a major role in the
regulation of CO
• Whenever sympathetic nervous activity increases eg during
exercise, it will stimulate both SA node as well as ventricular
myocardium
• This will increase both HR and FoC of muscles or SV. This will
in turn increase CO.
• If parasympathetic activity increases as during sleep, it will
inhibit SA node, thereby decreasing HR and CO.
3. Hormonal regulation of CO
• Whenever adrenaline level in the blood increases it
will stimulate SA node and ventricular myocardium.
• This will increase both HR and SV.
• This will in turn in increase CO.
 Limitation of CO
• There are definite limits to
the amount of blood that the
heart can pump, which is
expressed quantitatively in
the form of CO curves.
• Normal:
The plateau level of this
normal cardiac output curve is
about 13L/min.
• Hyper effective:
The uppermost curves are the
hyper effective herats that are
pumping better than normal.
Hyper effective heart plateau –
20L/min.
• Hypo effective:
The lowermost curves are for
hypo effective hearts that are
pumping at levels beloww
normal. Hypoeffective plateau
– 5L/min.
Hyper effective heart
• In this the heart is pumping
at a high rate and the cardiac
output increases.
• Two type of factors can make
the heart a better pump than
normal:
1. Nervous stimulation:
• It involves sympathetic
stimulation and
parasympathetic inhibition.
2. Hypertrophy of the heart muscles:
• It involves the increase mass and contractile strength
due to contractile strength due to exercise and
causing hypertrophy which allows increased CO.
Hypo effective heart
• In this the heart is pumping at
a very slow rate and the CO
decreases.
Factors that can cause hypo
effectivity are the following:
1. Increased arterial pressure
2. Inhibition of nervous excitation
3. Abnormal heart rhythm
4. Coronary artery blockage
5. Valvular heart disease
6. Congenital heart disease.
 Pathologically high or low CO
• In healthy humans , the average CO are surprisingly
constant from one person to another. However
multiple clinical abnormalities can cause either high or
low CO.
 High CO
• High CO is mostly caused by
reduced total peripheral
resistance.
Following are some of the
conditions that can decrease the
peripheral resistance and increase
the CO to above the normal.
1. Beriberi
2. Arteriovenous fistula
3. Hyperthyroidism
4. Anemia
 Low CO
• There are two factors that
cause low CO
A. Abnormalities that cause
the VR to fall too low
B. Abnormalities that cause
pumping effectiveness of
the heart to fail too low
References
• Guyton and Hall Textbook of Medical Physiology 13th Ed [2015] by
John E. Hall.
• Essentials of Medical Physiology, 6th Ed by K Sembulingam and Prema
• Text book of physiology – Dr AP Krishna
• Human Anatomy Physiology 7th Ed by Elaine N. Marieb and Katja
Hoehn
• CO = HR x SV
• HR decreased by PSNS stimulation
• Which decreases the SAN discharge, velocity of transmission and
decrease transmission speed through the AV bundle