Cardiac Output

Cardiac output is the volume of blood pumped by the heart per minute (mL
blood/min). Cardiac output is a function of heart rate and stroke volume. The
heart rate is simply the number of heart beats per minute. The stroke volume is
the volume of blood, in milliliters (mL), pumped out of the heart with each beat.
Increasing either heart rate or stroke volume increases cardiac output.
Cardiac Output in mL/min = heart rate (beats/min) X stroke volume (mL/beat)
An average person has a resting heart rate of 70 beats/minute and a resting
stroke volume of 70 mL/beat. The cardiac output for this person at rest is:
Cardiac Output = 70 (beats/min) X 70 (mL/beat) = 4900 mL/minute.
The total volume of blood in the circulatory system of an average person is about
5 liters (5000 mL). According to our calculations, the entire volume of blood
within the circulatory sytem is pumped by the heart each minute (at rest). During
vigorous exercise, the cardiac output can increase up to 7 fold (35 liters/minute)

Control of Heart Rate

The SA node of the heart is enervated by
both sympathetic and parasympathetic
nerve fibers. Under conditions of rest the
parasympathetic fibers release
acetylcholine, which acts to slow the
pacemaker potential of the SA node and
thus reduce heart rate. Under conditions of
physical or emotional activity sympathetic
nerve fibers release norepinephrine, which
acts to speed up the pacemaker potential of
the SA node thus increasing heart rate.
Sympathetic nervous system activity also
causes the release of epinephrine from the
adrenal medulla. Epinephrine enters the
blood stream, and is delivered to the heart
where it binds with SA node receptors.
Binding of epinephrine leads to further
increase in heart rate.

Control of Stroke Volume

Under conditions of rest, the heart does not fill to its maximum capacity. If the heart were to
fill more per beat then it could pump out more blood per beat, thus increasing stroke
volume. Also, the ventricles of the heart empty only about 50% of their volume during
systole. If the heart were to contract more strongly then the heart could pump out more
blood per beat. In other words, a stronger contraction would lead to a larger stroke volume.
During periods of exercise, the stroke volume increases because of both these mechanisms;
the heart fills up with more blood and the heart contracts more strongly.
Stroke volume is increased by 2 mechanisms:
1. increase in end-diastolic volume
2. increase in sympathetic system activity

End-diastolic Volume
An increase in venous return of blood to the heart will result in greater filling of the
ventricles during diastole. Consequently the volume of blood in the ventricles at the end of
diastole, called end-diastolic volume, will be increased. A larger end-diastolic volume will
stretch the heart. Stretching the muscles of the heart optimizes the length-strength
relationship of the cardiac muscle fibers, resulting in stronger contractility and greater
stroke volume.

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

An Increase in Sympathetic Activity Increases Stroke Volume

The cardiac muscle cells of the ventricular myocardium are richly enervated by sympathetic
nerve fibers. Release of norepinephrine by these fibers causes an increase in the strength of
myocardiall contraction, thus increasing stroke volume. Norepinephrine is thought to
increase the intracellular concentration of calcium in myocardial cells, thus facilitating
faster actin/myosin cross bridging. Also, a general sympathetic response by the body will

induce the release of epinephrine from the adrenal medulla. Epinephrine, like
norepinephrine will stimulate an increase in the strength of myocardial contraction and thus
increase stroke volume.

Blood Volume
Fluid Exchange Betweem Capillaries and Tissues
Capillaries are composed of a single layer of
squamos epithelium surrounded by a thin
basement membrane. Most capillaries (except
those servicing the nervous system) have pores
(spaces) between the individual cells that make
up the capillary wall. Plasma fluid and small
nutrient molecules leave the capillary and enter
the interstitial fluid through these pores, in a
process called bulk flow. Bulk flow facilitates
the efficient transfer of nutrient out of the blood
and into the tissues. However, blood cells and
plasma proteins, which are too large to fit

through the pores, do not filter out of the

capillaries by bulk flow.
Together, blood plasma and interstitial fluid make up the extracellular fluid (ECF). Plamsa
constitutes 20%, while interstitial fluid constitutes 80% of the ECF. The distribution of
extracellular fluid between these two compartments is determined by the balance between
two opposing forces: hydrostatic pressure and osmotic pressure.
The beating of the heart generates
hydrostatic pressure, which, in turn, causes
bulk flow of fluid from plasma to
interstitial fluid through walls of the
capillaries. In other words, the pressure in
the system forces plasma to filter out into
the interstitial compartment. The
composition of the interstitial fluid and the
plasma is essentially the same except that
plasma also contains plasma proteins not
found in the interstitial fluid. Because of
the presence of plasma proteins, the plasma
has a higher solute concentration than does
the interstitial fluid. Consequently, osmotic
pressure causes interstitial fluid to be
absorbed into the plasma compartment. In
other words, the plasma proteins drive the
reabsorption of water back into the
capillaries via osmosis.
The magnitudes of filtration and
absorption are not equal. The net filtration
of fluid out of the capillaries into the
interstitial compartment is greater than the
net absorption of fluid back into the
capillaries. The excess filtered fluid is
returned to the blood stream via the
lymphatic system. In addition to its roles in
digestion and immunity, the lymphatic
system functions to return filtered plasma
back to the circulatory system. The
smallest vessels of the lymphatic system
are the lymphatic capillaries (shown in
yellow). These porous, blind-ended ducts
form a large network of vessels that
infiltrate the capillary beds of most organs.
Excess interstitial fluid enters the
lymphatic capillaries to become lymph
fluid.

Lymphatic capillaries converge to form lymph

vessels that ultimately return lymph fluid back to
the circulatory system via the subclavian vein. The
presence of one-way valves in the lymph vessels
ensures unidirectional flow of lymph fluid toward
the subclavian vein.
If excess fluid cannot be returned to the blood
stream then interstitial fluid builds up, leading to
swelling of the tissues with fluid, this is called
edema.

Causes of Edema
1. Reduced concentration of plasma proteins. When the concentration of plasma proteins
drops, the osmotic potential of plasma drops, thus less interstitial fluid is absorbed into the
capillaries. The rate of filtration, however, remain unchanged. Therefore, the ratio of
filtration to absorption increases, leading to a build up of interstitial fluid. Any condition
that would lead to a reduction in plasma proteins could potentially cause edema. Examples
of conditions that reduce plasma proteins include:

Kidney disease can result in the loss of plasma proteins in the urine.
Liver disease can decrease the synthesis of plasma proteins.
A protein-deficient diet will decrease plasma proteins.
Severe burns result in a loss of plasma proteins (albumin) at the burn site

2. Increased capillary permeability. During an inflammatory response, tissue damage

leads to the release of histamine from immune cells. Histamine causes an increase in the
size of capillary pores. As capillaries become more permeable, the rate of filtration
increases.
3. Increase in venous pressure. If venous pressure is increased then blood dams up in the

upstream capillary bed, resulting in excess filtration. Examples of this condition include:

Left heart failure. The left half of the heart drains blood from the lungs. When the
left ventricle fails to adequately pump blood, venous pressure in the lungs increases.
This increase in hydrostatic pressure causes an increase in the rate of filtration of
fluid out of the capillaries and into the interstitial compartment. As a result, the
lungs fill with fluid, a condition called, pulmonary edema.
Standing still. If one stands still for long period of time, then blood will pool in the
veins of the legs. This will increase venous pressure and lead to weeping of fluid
into the tissues. You can actually feel your feet swell if you stand motionless for a
long time.

4. Blocked Lymphatics. If lymph vessels become blocked, then lymph fluid will not be
drained from the effected area and the area will swell. Any condition that causes blockage
or removal of lymph vessels can lead to edema. Examples of this condition include:

Filaria round worms are transmitted to humans by some species of mosquitos. The
worms migrate to the lymph vessels and block them. This causes dramatic swelling
of the effected area, a condition called elaphantiasis.

Treatment for breast cancer may include removal of lymph vessels from breast and
arms. This is done to limit the metastasis (spread) of cancerous cells to other parts of
the body through the lymph. Removal of lymph vessels results in swelling of the
effected area.

Regulation of Blood Volume by the Kidneys

The kidneys filter the blood and eliminate excess water and metabolic wastes by producing
and excreting urine. The daily volume of urine produced by the kidneys affects the amount
of ECF in the body and thus has a direct influence on blood volume. If the kidneys retain
water then blood volume rises. However, if the kidneys excrete large amounts of water then
the blood volume will decrease.
The regulation of water excretion by the kidneys is controlled, in large part, by antidiuretic
hormone (ADH). In the presence of ADH, the kidneys retain water. In the absence of ADH
the kidneys excrete more water. ADH is produced by the hypothalamus and secreted by the
posterior pituitary gland. The hypothalamus contains osmoreceptors that directly monitor
the osmolality of plasma. Plasma osmolality is high when plasma volume is low.
Osmoreceptors detect this condition and signal for the secretion of ADH. Retention of
water by the kidney restores blood volume to normal. ADH has the added effect of
stimulating thirst. Thus when your body needs water you are driven to seek water.