Cardiac output; Blood pressure &

regulation

T. O. Usman
Department of Physiology
CHS, UNIOSUN
Cardiac output
 Background
Background
• Cardiac output is the quantity of blood pumped
into the aorta each minute by the heart.
• This is also the quantity of blood that flows
through the circulation.
• It is usually calculated by multiplying the stroke
volume by the heart rate (SV*HR) and has an
average value of 5L/min in a resting adult.
• Therefore, the cardiac output can be regulated by
regulation of the stroke volume and heart rate.
 Background
Regulation of stroke volume
• The stroke volume is affected by three factors
• Preload
• Afterload
• Inotropy
• Preload can be defined as the initial stretching of
the cardiac muscle prior to contraction.
• It is usually determined by the end-diastolic
volume
 Background
Regulation of stroke volume
• The most important factor affecting the preload
and subsequently stroke volume is the venous
return i.e. the volume of blood being returned to
the heart by the veins.
• An increase in venous return increases ventricular
filling which leads to increased EDV and increased
preload.
• Increased preload enables the heart to eject a
higher stroke volume via the Frank-Starling
mechanism.
 Background
Regulation of stroke volume
• Other important factors that affect preload
include
– Heart rate, through its influence on filling time, has an
inverse effect on preload.
– Atrial contraction: At high heart rates, however,
increased atrial contractility (owing to sympathetic
activation) significantly enhance (up to about 40%) the
contribution of atrial contraction to ventricular filling,
thereby helping to maintain preload.
 Background
Regulation of stroke volume
 Background
Afterload
• Afterload is the “load” against which the heart
must contract to eject blood. A major component
of the afterload for the left ventricle is the aortic
pressure.
• The greater the aortic pressure, the greater the
afterload on the left ventricle.
• Therefore, the greater the afterload, the lesser
the stroke volume.
 Background
Inotropy
• Inotropy is the contractility of the cardiac muscle.
• Change in inotropy occurs mostly due to sympathetic
stimulation of the cardiac muscle.
• This leads to increased calcium entry into the cell.
• An increase in inotropy leads to an increase in force
of ventricular contraction and increased stroke
volume.
• Changes in inotropy also affects the ejection fraction
which is defined as the stroke volume divided by the
end-diastolic volume.
• Therefore, increased inotropy increases ejection
fraction, whereas decreased inotropy decreases
ejection fraction.
 Background
Inotropy
• Increase in inotropic state is particularly
important during exercise as it helps to maintain a
high stroke volume at high heart rates.
• Factors that affect inotropy are
increased/decreased sympathetic activation.
 Measurement of cardiac output
Background
• Doppler echocardiography;
– Used to measure SV which is then multiplied by HR. It
is non-invasive
• Dye dilution method
– Involves injecting a dye e.g. LiCl, into the veins and
measuring its conc. In the arteries.
• Thermodilution method
– Involves injecting a cold (0 degrees) bolus of saline and
measuring the temperature at a known distance
downstream
• Fick's principle:
 Measurement of cardiac output
Background
• Fick's principle:
• The difference between the amount of oxygen
leaving lungs by arterial blood during one minute
and the amount entering lungs by venous blood
during same time is equal the amount of oxygen
extracted from the breathed air.
• It is invasive VO2
Q=
CaO2 – CvO2
Q: cardiac output
VO2: O2 consumption
CaO2:arterial O2 content
CvO2: mixed venous O2 content
 Measurement of cardiac output
Background
• Non-invasive Fick's method:
– Involves measurement of carbon dioxide via
measurement of end tidal CO2
 Measurement of cardiac output
Background
• Magnetic resonance: Resonance properties of
protons in the nucleus do change with respect to
velocity. Thus, magnetic resonance can be used as
an accurate way to measure the flow in aorta
(cardiac output).
• The method is expensive, it is only used in
research.
 Diseases associated with cardiac output
Background
• These can be classified into those that cause
abnormally high or low cardiac output.
• Those that cause high cardiac output are all
associated with reduction in total peripheral
resistance. They include
 Diseases associated with cardiac output
Background
• Beriberi (lack of Vit B1, diminished ability of the
tissue to use nutrients leading to compensatory
vasodilation).
• Arteriovenous fistula/shunt (flow of blood directly
from a major artery to vein therefore increasing
venous return).
• Hyperthyroidism (increased metabolism).
• Anemia (reduced blood viscosity and oxygen
supply leads to compensatory vasodilation)
Diseases associated with cardiac output
Background
Diseases that lower cardiac output include
• Coronary blood vessel blockage
• Severe valvular heart disease
• Myocarditis
• Decreased blood volume
• Acute venous dilation
• Obstruction of the large veins
– The first 3 are cardiac factors while the others are
peripheral factors.
Blood pressure and
regulation
 Background
Blood pressure
• This is the force exerted by the blood upon a vessel
wall.
• It is measured as the systolic blood pressure over the
diastolic blood pressure and the unit of measurement
is millimeter of mercury.
• Systolic pressure is the maximum pressure exerted in
the aorta when blood is ejected into them during
systole while diastolic pressure is the minimum
pressure in the aorta just before the ventricles ejects
blood into the aorta.
• The difference between systolic and diastolic
pressure is the pulse pressure.
 Blood pressure regulation

• Short term
– Baroreceptors
• Long term
– Kidney via renin angiotensin system
 Baroreceptors
Baroreceptors
• Baroreceptors are spray-type nerve endings that lie
in the walls of the arteries; they are stimulated
when stretched.
• A few baroreceptors are located in the wall of
almost every large artery of the thoracic and neck
regions; but, are extremely abundant in
– the wall of each internal carotid artery slightly above
the carotid bifurcation, an area known as the carotid
sinus, and
– the wall of the aortic arch.
 Location of
baroreceptors
• Baroreceptors sense stretch and rate
of stretch by generating action
potentials (voltage spikes)

• Located in highly distensible regions

of the circulation to maximise
sensitivity

http://www.cvphysiology.com/Blood Pressure/bp012 baroreceptor anat.gif

 Baroreceptors
• After the baroreceptor signals have entered the
tractus solitarius of the medulla, secondary signals
inhibit the vasoconstrictor center of the medulla
– And also excite the vagal parasympathetic center.
• The net effects are
(1) vasodilation of the veins and arterioles throughout the
peripheral circulatory system and

(2) decreased heart rate and strength of heart contraction.

 Baroreceptors
• Therefore, excitation of the baroreceptors by high
pressure in the arteries reflexively causes the
arterial pressure to decrease because of both a
decrease in peripheral resistance and a decrease in
cardiac output.

• Conversely, low pressure has opposite effects,

reflexively causing the pressure to rise back toward
normal.
 Baroreceptors
• The baroreceptors are also important in maintaining
relatively constant arterial pressure in the upper body
when a person stands up after having been lying down.
• This is because immediately on standing, the arterial
pressure in the head and upper part of the body tends to
fall, and marked reduction of arterial pressure could cause
loss of consciousness.
• However, the falling pressure at the baroreceptors elicits
an immediate reflex, resulting in strong sympathetic
discharge throughout the body.
• This minimizes the decrease in pressure.
– Baroreceptor response is a negative feedback response
 Baroreceptor reflex
Blood pressure falls

Sensors Aortic arch Carotid sinus

Neural integration Nucleus tractus solitarius

Vasoconstriction Cardiac stimulation Cardiac inhibition

Effectors Constriction of veins Increased stroke Increased heart

& arterioles volume rate

Increased peripheral Increased cardiac

resistance output

Increased blood
pressure
Long term
Long termcontrol ofblood
control of blood pressure
pressure
• Involves control of ECF volume and sodium balance
by the kidneys.
• If there is an increase in extracellular fluid volume,
there would be a commensurate increase in blood
volume, which increases venous return of blood to
the heart.
• This leads to an increase in cardiac output, which
increases arterial pressure.
• The increased cardiac output also indirectly causes an
increase in total peripheral resistance through
autoregulation of blood flow to the tissues.
Long term control of blood pressure
• The increase in ECF volume is primarily influenced by
sodium concentration.
• This is because whenever there is excess sodium in the
ECF, it stimulates the thirst center in the brain, which
makes the individual drink more water so as to return the
ECF sodium concentration to normal leading to an
increase in ECF volume.
• Excess sodium in the ECF also stimulates the posterior
pituitary gland to secrete an hormone called antidiuretic
hormone or vasopressin.
• Antidiuretic hormone causes the kidneys to reabsorb
more water from the renal tubules, thereby reducing
urine output and increasing ECF volume.
 Renin/angiotensin system
• It is one of the most important mechanism by which
the kidneys regulate long term control of blood
pressure.
• It is initiated by the release of renin from the JG cells
of the kidney in response to a decrease in blood
pressure.
• Renin acts enzymatically on a plasma protein called
angiotensinogen to convert it into angiotensin 1.
• Angiotensin 1 is in turn converted to angiotensin 2
by the action of angiotensin converting enzyme
which is found exclusively in the lungs.
• Angiotensin 2 acts in two ways.
 Renin/angiotensin system
Renin/angiotensin system

• First it causes vasoconstriction of several

arteries/arterioles in different parts of the body
thereby increasing TPR and subsequently BP.
• Secondly, it acts directly on the kidneys to reduce
salt and water excretion thereby increasing ECF
volume then BP.
• It also stimulates the release of aldosterone from
the adrenal glands which leads to increased salt
and water reabsorption from the renal tubules
leading to increased ECF volume and BP
 Renin/angiotensin/
Reduced renal
blood flow
aldosterone system
Increased
Juxtaglomerular blood volume
apparatus LV filling pressure)

Increased
Renin Fluid re-absorption pre-load

(LV pressure
Angiotensinogen Sodium retention
beginning of systole)

Increased
after-load
Angiotensin I
Increased aldosterone
Angiotensin II secretion

Veins
vasoconstriction
Arteries
 Hypertension
Hypertension
• It is a sustained elevation in blood pressure.
• It is generally classified into 2; primary/essential
and secondary hypertension.
• Primary hypertension is of an unknown origin but is
thought to be hereditary while secondary is usually
due to some underlying factor such as tumor of the
JG cells.
• Excess weight gain and sedentary lifestyle are some
of the most important risk factor for primary
hypertension and it is characterized by increased
CO, increased SNS activity, increased ang 2 and
aldosterone secretion.
 Hypertension
Hypertension
• Treatment is usually by lifestyle modification.
• However, vasodilator, diuretic and sympathoplegic drugs
may be used to treat it.