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Lecture 7: Heart Failure and Blood Flow

1. Heart Failure

Heart failure is any reduction in the heart's function that prevents it from maintaining adequate
cardiac output.

1a. Heart Failure Illustrated on a Starling Curve

Heart failure can be illustrated on a Starling curve which plots stroke volume (SV) as a function
of end-diastolic volume (EDV). The curves below illustrate that heart failure leads to a reduction
in SV at any given EDV. This can be partially offset by sympathetic stimulation which can
enhance ventricular contractility (thereby increasing SV) and can also increase heart rate.
Increases in SV and heart rate (HR) lead to increases in cardiac output (CO = HR X SV). The
figure below illustrates that it takes a smaller EDV to achieve a normal SV when sympathetic
stimulation (the middle purple curve) is added to a failing heart (the lower red curve) although it
doesn’t bring SV all the way back to the level seen in a normal heart (the upper green curve).
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1b. Causes of Heart Failure

There can be many reasons for heart failure. Among the most common causes of heart failure is
myocardial infarction, or a heart attack. This occurs when cardiac myocytes die due to a
blockage of the coronary arteries. These blockages can be caused by fatty deposits or plaque, and
generally begin to show effects as ischemia, or reduced blood flow. This can lead to the death of
cardiac muscle tissue due to lack of oxygen, and this necrotic tissue inhibits heart function,
causing a heart attack.

Long-term high blood pressure can also cause heart failure as can stenosis (failure of the
semilunar valves to open properly). High blood pressure increases cardiac workload, causing
cardiac hypertrophy, a loss of ventricular compliance, a reduction in end-diastolic volume, and a
decrease in both stroke volume and cardiac output. Thus, long-term high blood pressure is a
serious medical condition. The same is true with stenosis. If blood flow out of the aorta is
reduced due to the narrow valve opening then the heart muscle grows in order to compensate for
this.

Anything that reduces ventricular contractility can cause heart failure, as can anything that
obstructs an AV valve. As well, third degree heart block over a long period of time may cause
heart failure, as it decreases heart rate and increases end-diastolic volume, leading to chronic
overstretching and weakening of the heart.

Symptoms of heart disease include difficulty breathing, fatigue, chest pain, dry hacking coughs,
swelling of the extremities, cyanosis (a blue complexion due to lack of oxygenation of the
arterial blood), and a weak pulse. Note that throughout the lectures there are times when lists of
symptoms are indicated. These lists of symptoms will not be on the exam.
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1c. Heart Failure Illustrated on a Ventricular Pressure-Volume Loop

The ventricular pressure-volume loop below on the left illustrates the function of a normal heart
(pink loop; left) as well as the function of a heart during acute heart failure (blue loop; middle)
and chronic heart failure (green loop; right).

When the heart is failing it isn’t pumping blood efficiently. End-systolic volume (ESV) increases
since the heart is incapable of pumping normal amounts of blood from the ventricles so more
blood than normal gets “left behind” in the ventricle.

End-diastolic volume (EDV) also increases since the heart is usually beating at a slower rate than
normal leading to enhanced filling time. Also, the inefficient pumping that leads to increases in
ESV also contributes to the increases in EDV because there is more blood in the ventricles
(higher ESV) to begin with once the heart begins its filling phase (i.e., the section marked “a” on
the diagram on the right).

Since the increase (with heart failure) if ESV is greater than the increase in EDV, stroke volume
decreases since SV equals EDV minus ESV. The effects are exacerbated in chronic heart failure
compared to acute heart failure.

The reduction in contractility is also illustrated by the decrease in the slope of the end-systolic
pressure-volume relationship (ESPVR).
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1d. Left and Right Heart Failure

Heart failure illustrates a number of important physiological concepts that relate not only to heart
function, but to kidney function and osmotic regulation as well. We can look at heart failure from
either the left or the right: both sides can fail, with the left heart failing to pump enough blood to
the systemic circulation, and the right heart failing to do the same for the lungs, and these
produce different symptoms.

Left heart failure is particularly troublesome, as one problem leads to another in a cascade effect.
If the left ventricle loses the ability to contract properly, this will cause blood coming from the
lungs via the pulmonary vein into the left atria to “back up”, causing essentially a 'traffic jam' in
the pulmonary vein. Pressure then builds in the capillaries in the lungs, and this pressure buildup
can cause fluid leakage in the lungs. Fluid can get into the alveoli leading to lung tissue collapse
and reduced gas exchange causing, at its worst, suffocation. This condition is called pulmonary
edema.

However, it continues to get worse: if the left ventricle doesn't function properly, pressure in the
aorta and systemic circulation will decrease, due to the decrease in cardiac output. A drop in
blood pressure is a trigger for the kidneys to retain water (this is one reason why a high-salt diet
is harmful - it causes the body to retain extra fluid to maintain osmolarity, but this has the effect
of raising blood pressure). This fluid will be predominately found in the venous system, because
our veins are what we call volume reservoirs. This increases pressure in the pulmonary artery.
Thus the lungs are being subject to increased pressure on both the output side (pulmonary vein)
and the input side (pulmonary artery). This condition is referred to as congestive heart failure.
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We can see left heart failure and right failure by looking at the distribution of blood in the
cardiovascular system and the movement of fluid from capillaries to tissues (in the lungs, for left
heart failure; in the systemic tissues, for right heart failure).

In a normal distribution of blood, most of the volume of blood is in the venous system, with
comparatively little in the arteries. There is an equal amount in both the right and left sides of the
heart.

In a heart with left heart failure, there is a large buildup of blood in the pulmonary circulation,
and a correspondingly large increase in the volume of blood on the left side of the heart.

In right heart failure, most of the blood pools in the systemic venous circuit leading to systemic
edema; as well, there is a similar buildup of blood in the right side of the heart.
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1e. Systolic and Diastolic Dysfunction

Heart failure can also be looked at from the perspective of systolic and diastolic dysfunction.

In systolic dysfunction, the ventricles are stretched, enlarged, and weaker than normal; and
when they pump, they output less than 40%-50% of the blood in the ventricle. Normally, the
amount is about 60%.

Diastolic failure is when the ventricles are stiff, and fill with less blood than normal. Whilst the
ventricles may pump out 60% of their capacity, as normal, the actual amount, due to decreased
volume of blood, will be far lower.
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2. Blood Flow

2a. Measuring and Calculating Blood Flow

There are several modern methods of measuring blood flow. Ultrasonic probes are one method,
involving sensors placed upon the surface of the skin just above blood vessels, which use
ultrasound to measure the flow of blood beneath them. Another method involves the use of blood
flow probes actually placed around arteries, implanted during surgery. These give a direct
measurement of blood flow, and are used during carotid artery surgery to give the most accurate
possible measurement.

Finally, MRIs can be used to measure blood flow, and they are generally used for studying blood
flow to sensitive organs such as the brain.

We can calculate blood flow (BF) by taking changes in pressure (ΔP) or the pressure gradient,
and dividing this by resistance (R) to flow (BF = ΔP/R). The pressure gradient is the difference
between the high and low pressures at opposite end of a system (in this case, the blood vessels),
and it is thus the driving force for blood flow.

2b. Different Types of Blood Vessels

The amount of resistance (to flow) in a blood vessel is dependent upon the type of vessel.
Starting out of the muscular aorta, arteries are large, muscular, and highly elastic. Arterioles,
which branch off arteries, are smaller, but still muscular, and well innervated. Capillaries, the
smallest of blood vessels, are thin-walled and highly permeable. Arterioles and capillaries are the
primary sites of resistance to flow in the systemic circulation. Capillaries connect to venules,
which are thin-walled with some smooth muscle. Finally, venules connect to veins, which are
thin-walled (compared to arteries), fairly muscular, and highly distensible, and veins connect to
the vena cava and back into the heart.

Arteries are what we call pressure reservoirs, because they are much higher in pressure than the
venous system. Veins are volume reservoirs, because most of the volume of blood is contained
within them.
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2c. Vascular Compliance

We can define compliance as the capacity to distend or stretch or fill. If we look at a blood
vessel as just being a tube, what we are interested in is the pressure inside the tube, and the
pressure just outside it. The difference between these two values is the pressure gradient
(distending pressure; transmural pressure). If the pressure on the outside is greater than the
pressure on the inside, the blood vessel will contract; if the opposite is true, it will expand.

The relationship between volume and distending pressure is not linear. At higher pressures,
vessels become less and less compliant. At low pressures, veins have far greater compliance than
arteries - however, at higher pressure their ability to distend is quite similar. Since at higher
pressures venous compliance is similar to arterial compliance, it makes veins suitable to serve as
arterial bypass grafts in heart bypass surgery.
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2d. Distribution of Blood in the Circulation

Under healthy conditions, approximately 61% of the five litres of blood in the body is found in
the systemic veins and venules, with 9% in the heart, 7% in the arterioles and capillaries, 11% in
the systemic arteries and 12% in the pulmonary circulation. However, the vast majority of the
(blood) pressure in the circulatory system is found on the arterial side.
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2e. Pressure Drops within the Circulation

The greatest pressure differential (or pressure decrease) in the systemic circulation is between
the arteries and the arterioles and to some extent the capillaries. This occurs because the
arterioles and capillaries are the two greatest sites of resistance to blood flow in the systemic
circulation.

In the pulmonary circuit the same is true; the greatest pressure drops are in the arterioles and
the capillaries. However, the pressure is far less in the pulmonary circuit than it is in the
systemic circuit. This is due to the need to protect delicate lung tissue from high pressures. High
blood pressure in the lungs would force fluid from blood vessels into the alveoli and cause
pulmonary edema.

However, blood flow between these two circuits is equal - and this means that resistance to flow
in the pulmonary circuit must be lower than it is in systemic circuit (see below).
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2f. The Driving Forces for Blood Flow

Mean arterial pressure (MAP) is the driving force for blood flow in the systemic circulation.
Systemic blood flow is driven by the difference between mean arterial pressure (i.e., pressure in
the aorta) and central venous pressure (pressure in the vessels emptying into the right atria).
However, given that central venous pressure is very close to zero (and we approximate it to be
zero for these purposes), we only really need to consider mean arterial pressure when calculating
blood flow in the systemic circuit. In other words, MAP is the driving force for blood in the
systemic circulation.

The driving force for blood flow in the pulmonary circulation follows the same principle
although the pressure in this circuit is far lower. The pressure gradient driving blood flow here is
the pressure in the pulmonary artery (leaving the right ventricle and heading to the lungs) minus
pressure in the pulmonary vein (emptying into the left ventricle). Pulmonary artery pressure is
approximately 15 mmHg while pulmonary venous pressure (in the pulmonary vein) can be
approximated to be zero.
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2g. Resistance to Blood Flow

Blood flow equals the pressure gradient divided by the resistance to blood flow. There are a
number of factors that influence the resistance to flow. We look at resistance from two points of
view: from that of a single blood vessel and from that of the circulatory system as a whole.
Resistance to blood flow in the circulation as a whole is called total peripheral resistance.

Resistance is the degree to which blood flow is hindered. The relationship between pressure and
resistance is as follows: for any given change in the pressure gradient, if resistance increases,
then the flow of blood will decrease, and vice versa. Thus blood flow follows the formula of
blood flow (BF) = change in Pressure (ΔP)/Resistance (R). However, this is only true of a single
blood vessel. From the point of view of the entire system, increasing blood pressure actually
(usually; i.e., in the absence of compensatory reflexes) increases blood flow. When we come to
blood pressure regulation, taking the entire circulatory system into account becomes more
important.
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2h. Factors Affecting Resistance to Blood Flow

In a single blood vessel, there are four main factors which can affect the amount of vascular
resistance. The first is the radius of the vessel itself. Generally the narrower the vessel the
greater the resistance to blood flow. For example, there is far more resistance in arterioles and
capillaries than there is in veins and arteries since arterioles and capillaries are narrower than
arteries and veins.

The magnitude of resistance to flow can be altered by having the vascular smooth muscle which
surrounds blood vessels either constrict or dilate. Constriction narrows the vessel and reduces
flow. Dilation widens the vessel and increases flow.

Constriction and dilation are regulated by adrenergic innervation and by circulating epinephrine
and norepinephrine. As we will see later, the radius affects resistance to the fourth power, so it
has a very large effect on flow. However, although the radius of the blood vessel is the primary
regulator of resistance, there are other factors involved.

Note that you do not need to know the diameters listed in the chart below although you should
know which vessels are “large and which are “small”. You do need to know the functions of the
various vessels.

The length of the blood vessel is another factor that determines resistance. The longer a vessel is
the more resistance to flow it has. However, this is not something that is physiologically
regulated; vessel length will change as the body grows but on a day-to-day basis it is an
unchanging factor.
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The viscosity of the blood also affects resistance. Viscosity is a measure or index of the internal
friction of adjacent fluid layers sliding past one another, as well as the friction generated between
the fluid and the wall of its vessel. An important factor in determining blood viscosity is what is
termed haematocrit, which refers to the percentage of blood volume occupied by blood cells,
both red and white.

Normally haematocrit is about 45% - the rest of the blood volume is comprised of plasma. As
haematocrit increases, so does viscosity.

Another factor influencing blood viscosity is temperature - for every degree Celsius the
temperature drops, blood viscosity increases by approximately 2%. As body temperature remains
mostly constant, this is not a particularly strong influence on flow, except in those blood vessels
very close to the surface of the skin.

Finally, flow rate can influence viscosity: as flow rate decreases, viscosity increases. This is due
to an increase in cell to cell and protein to cell interactions that cause red blood cells to adhere to
one another.

The final factor that affects vascular resistance is the ratio of laminar to turbulent blood flow.
Laminar flow refers to blood flow that is smooth and even, and travelling in a single direction
within the blood vessel. Laminar flow will create a “cone” of concentric layers of fluid, with the
velocity of fluid fastest in the center. With turbulent flow, the opposite is true: blood flow is
chaotic and disordered. There is backflow, and it almost resembles rapids in a river. Turbulent
flow is not especially common, but in unhealthy vessels with large amounts of plaque or fatty
deposits, it can occur. Turbulent flow can also come from the heart, if the valves are diseased or
the aorta has stenosis. Turbulent flow can also occur at branch points in blood vessels and in
cases where blood flow is very rapid.