1

Lecture 8: Blood Flow

1. Blood Flow Continued (See lecture 7 notes for the starting slides)

Blood flow (BF) = Change in Pressure (ΔP)/Resistance (R)

1a. Poiseuille’s Law

We can calculate resistance (R) to blood flow along a blood vessel using Poiseuille's Law: R = 8Lη /
πr4

In this equation, R is resistance, L is blood vessel length, η is viscosity and r is radius. By looking at
this equation, we can see that if viscosity increases, resistance increases. If the pressure gradient
remains constant then blood flow will decrease. If the radius of the vessel increases, then resistance
decreases. If pressure remains constant then blood flow will increase.

Given that radius is to the fourth power in this equation, it exerts large an effect on resistance. Doubling
the radius reduces the resistance to 1/16th its original level, whilst flow is increased 16 times.

1b. Total Peripheral Resistance

Poiseuille’s Law holds true for a single blood vessel. However, when we look at the circulatory system
as a whole, we no longer look at the resistance in the same way as if it were in a single vessel. Instead
we look at total peripheral resistance, which is the combined resistance of all blood vessels within the
systemic circulation. The vast majority of this total peripheral resistance, the so -called resistance
vessels, is within the arterioles and capillaries. The resistance of these vessels can be changed by the
contraction or relaxation of rings of smooth muscle wrapped around these vessels. These rings of
smooth muscle are under nervous and hormonal control and are innervated by the sympathetic nervous
system and affected by circulating epinephrine and norepinephrine. These hormones can cause
different effects on blood vessels depending on the situation (see lecture 9).
 2

1c. Blood Flow and Resistance in the Pulmonary and Systemic Circuits

There are two “circuits” of blood within the body: the systemic circuit and the pulmonary circuit,
with the systemic circuit having a much higher pressure than the pulmonary circuit. The low pressure
in the pulmonary circulation is important in protecting the delicate lung tissue and preventing
pulmonary edema. However, blood flow in both circuits is equal; otherwise there would be a buildup of
blood in one part of the circulation. So, necessarily, we can infer that resistance in the pulmonary
circuit must be much lower than resistance in the systemic circuit, in order for the pulmonary circuit to
maintain a lower pressure than, but equal blood flow to, the systemic circulation.
 3

We can model blood flow throughout the body by looking back at our equation for blood flow in a
single blood vessel, Flow = ΔP/R. Remember that cardiac output (CO) is the amount of blood pumped
per minute. Given that the entire CO flows through the systemic circuit, we can say that CO = blood
flow. Now, if mean arterial pressure (MAP) is the virtually the same after subtracting venous pressure,
and MAP drives blood flow in the systemic circuit, then MAP = ΔP. Finally, in our new equation R =
total peripheral resistance (TPR). So, our new equation is

CO = MAP/TPR

As well, as we know that cardiac output is equal to stroke volume X heart rate, it gives us an easy way
to calculate mean arterial pressure: MAP = SV x HR x TPR. Thus, we can see that every factor that
affects blood pressure is really working upon one of these three variables: stroke volume, heart rate or
total peripheral resistance (or blood volume which is regulated by the kidney).
 4

1d. Patterns of Blood Flow

Blood flows between the two circuits, pulmonary and systemic, is in series - for example, starting from
the left ventricle, blood goes through the aorta, across the systemic circuit, into the venous system, and
back to the right side of the heart through the vena cava, where is pumped by the right ventricle through
the pulmonary artery to be re-oxygenated by the lungs: and the cycle begins again.

However, within any one of these circuits (and we'll use the systemic circuit as an example), blood
flow is parallel. This is to say, no organs receive deoxygenated blood (the liver is an exception). Every
organ has its own independent blood flow, which is independently regulated. There is an independent
'circuit-within-a-circuit' going to the brain, as well as another to the kidneys, to the skin, etc.
 5

This also means that when there is a need to increase blood flow to a specific part of the body, for
example, to muscles and skin during exercise, the proportion of blood flowing to the skin and skeletal
muscle increases dramatically, whilst blood flow to other organs decreases accordingly (however,
cardiac output increases as well, so for example the brain does not actually become deprived of blood).

Blood flow within individual organs is in parallel as well: different parts of the same organs all receive
blood that is equally oxygenated. The exception to this is the liver - blood from the intestines goes
directly into the liver due to the need for nutrients that were absorbed in the gut to be sent directly into
the liver for processing. However, the liver itself has its own, secondary circuit, to provide oxygenated
blood (see digestive system lectures).
 6

1e. Resistance to Blood Flow in a Parallel Circuit

One advantage of parallel circuits is that such an arrangement of vessels greatly reduces overall
resistance to flow. Remember, resistance is affected by vessel radius to the fourth power, so the
combination of small parallel vessels produces much less resistance than one large vessel would. The
total resistance of a network of parallel vessels is less than the resistance of the vessel having the lowest
resistance. As well, when there are many parallel vessels, changing the resistance of a small number of
these vessels has little effect on resistance of the segment as a whole.
 7

1f. Local (Intrinsic) Control of Blood Flow

Blood flow regulation to individual organs is accomplished by vasoconstriction or vasodilation of the

smooth muscle rings around blood vessels. This can be controlled by adrenergic receptors (receptors
for adrenaline and noradrenaline), either alpha (cause constriction) or beta (cause dilation). The
proportion of both receptors on any given vessel determines whether the ring of smooth muscle
constricts or dilates in response to adrenergic stimulation.

However, blood flow can also be intrinsically controlled, by different and changing metabolic demands
in tissues. These rings of smooth muscle can contract or relax directly in response to changes in levels
of oxygen and carbon dioxide, as well as other local chemicals like histamine and nitric oxide. Some
blood vessels are directly sensitive to changes in pressure that cause them to stretch, again affecting
blood flow - this is called a myogenic response, and is important in delicate tissue such as the brain and
kidneys.
 8

Oxygen: Oxygen diffuses into metabolically active tissue from the blood via the extracellular fluid. At
steady state, O2 consumption is equal to the rate of O2 delivery. If metabolic rate increases, then the
tissues require more oxygen. In a direct response to a lack of oxygen in the extracellular fluid the rings
of smooth muscle around the nearby blood vessels will relax (vasodilate). When cells need more
oxygen than is being delivered, this is called ischaemia. Vasodilation leads to increased blood flow.
The tissue therefore receives an increased supply of oxygen. This enhancement of blood flow in
response to an increase in metabolic rate is called active hyperaemia.

See the Power Point slides for the entire scheme of reduced oxygen induced changes in blood flow.

The diagram below illustrates the sequence of events that occur in active hyperaemia.
 9

Carbon Dioxide: A similar process happens with carbon dioxide. Generally, tissues will be in a steady
state, where CO2 removal is equal to CO2 production. However if the metabolic rate increases, or blood
flow decreases, and CO2 production exceeds CO2 removal then this will cause vasodilation to increase
blood flow and return the tissues to a steady state where production equals removal. Also, since carbon
dioxide causes acidification, any decrease in pH will also cause vasodilation; so too will any increase in
potassium, or lactic acid. This process is also a manifestation of active hyperaemia.

See the Power Point slides for the entire scheme of increased CO2 induced changes in blood flow.
 10

Reactive hyperaemia is an increase in blood flow in response to previous reduction in blood flow. It is
essentially a rebound increase in blood flow triggered by a previous lack of blood flow.

Myogenic Smooth Muscle: Another form of local control over blood flow is caused by the stretching
of smooth muscle. Some, but only some, vascular smooth muscle is stretch-sensitive - particularly in
sensitive organs such as the brain. As blood pressure increases, the smooth muscle contracts and the
vessels constrict, protecting them from pressure-induced damage and the possibility of edema.

When the blood pressure lowers, the muscles relax and the vessels dilate, restoring blood flow. This
type of muscle is called myogenic muscle, and this process a myogenic response. This response also
works in reverse, to protect sensitive organs against very low blood pressure.
 11

Nitric oxide: Nitric Oxide is produced by nitric oxide synthase in endothelial cells and nerves. Nitric
oxide acts upon guanylyl cyclase to produce cGMP, and cGMP causes vasodilation and increases blood
flow.

Phosphodiesterase 5 (PDE5) breaks down cGMP, allowing blood flow to fall to normal levels. This is
the fundamental working principle behind Viagra - there are 13 different phosphodiesterases, but PDE5
is found only in the penis. Viagra inhibits PDE5, meaning that blood flow to the penis remains
increased. Recently it has been discovered that Viagra can also prevent cardiac hypertrophy, perhaps
due to a similar sort of mechanism.

Endotoxin and Septic Shock: Another vasodilator which is observed under clinical conditions is
endotoxin, which is present during certain bacterial infections. Endotoxin, a bacterial
lipopolysaccyhaaride, activates nitric oxide synthase in macrophages, producing nitric oxide and
causing vasodilation and lowered blood pressure. This drop in pressure is called septic shock, and has
a 50-70% mortality rate. “Shock” refers generally to a state in which blood pressure is too low to
sustain life.
 12

1g. Summary Diagram of Extrinsic and Intrinsic Control of Blood Flow

This diagram won’t be shown in the lecture. It is a useful summary of some of the factors that cause
blood vessels to dilate or constrict. Extrinsic hormonal mechanisms will be discussed in lecture 9.
 13

2. The Fetal Heart (Moved to lecture 9 in 2024)

The fetal heart receives blood from the placenta via the umbilical vein that joins with the inferior vena
cava. This blood enters the right atria.

However, rather than all of this blood then moving into the right ventricle (from which it would be
pumped to the lungs), some of the blood moves through an opening between the right and left atria
called the foramen ovale. The consequence of this is that this blood does not go to the lungs; rather, it
flows from the right atria to the left atria to left ventricle and then to the systemic circulation via the
aorta. This is referred to as a right to left shunt. The blood is shunted from the right side of the heart
to the left side of the heart. The reason for this is that the lungs are not involved in gas exchange in
utero so there is no reason to send blood to the lungs.
 14

Some of the blood in the right atria does move into the right ventricle. The blood in the right ventricle
leaves via the pulmonary artery. Some of the blood in the pulmonary artery does flow to the lungs.
Even though they are not involved in gas exchange, the lung tissue still needs oxygen and nutrients
supplied by blood. However, some of the blood that flows upward through the pulmonary artery
moves into the aorta via a second opening called the ductus arteriosus. This also helps to minimise the
amount of blood flowing to the lungs.
 15

At birth, the foramen ovale and ductus arteriosus close (there is a flap of tissue that covers them and
eventually fuses with the surrounding tissue. The events that cause this are initiated by the first few
breaths that are taken immediately after birth (or at the time during birth that the baby starts to breathe
air). Once air is in the lungs, the lungs inflate. This causes a reduction in the resistance to blood flow in
the pulmonary circulation. As more blood flows into the lungs, there is more blood available to move
to the left side of the heart and into the systemic circulation. At this point the systemic pressure
increases. This pressure increase in the aorta causes aortic pressure to become greater than pulmonary
artery pressure causing the closure of the ductus arteriosus. Simultaneously, the greater pressure in the
left atria compared to the right atria causes the foramen ovale to close.

Failure of the ductus arteriosus to close can lead to a backflow of blood from the aorta into the
pulmonary artery. This can lead to pulmonary blood flow being greater than systemic blood flow. As a
result of the reduction in blood flow in the systemic circulation, the left ventricle has to work harder to
maintain systemic flow. It undergoes hypertrophy (grows) which can lead to weakening of the muscle
and a reduction in the ability to pump blood.