Download RUN FOR YOUR LIFE By LORELA BERBERI

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RUN FOR YOUR LIFE
By
LORELA BERBERI
_____________________
A Thesis Submitted to the Honors College
In Partial Fulfillment of the Bachelor’s Degree
With Honors in
Physiology
THE UNIVERSITY OF ARIZONA
MAY 2016
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Table of Contents
Abstract ……………………..…………………………………………………..….2
The heart …………..………………………………………………………..….…..3
The Vessels ……………………………………….………………..………..……..9
Blood ………………………………….………………………….………………14
Coronary Artery Disease ………………...……………………………………….16
Running ………...…………………………….…………………………………..21
Running and the Heart ………….…………………………………………….…..26
From Couch to 5K………...………………………………………………………29
Sources Cited…..…………...………………………………………………..……31
Appendix……………………………………………………………………….....34
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Abstract
It is well known that cardiovascular diseases cause a great number of deaths around the world
but to emphasize how great an issue it is, cardiovascular diseases (CVDs) are considered the
number one cause of death globally. An estimated 17.5 million people died from CVDs in 2012.
That represents 31% of all global deaths1. However, this is a relatively preventable disease with a
moderation of diet and the uptake of aerobic exercise such as running. A literature review was
employed in order to gather data about the pros and cons of running on cardiovascular health.
We demonstrated that running can significantly reduce the risks of cardiovascular disease but not
eliminate diseases completely. In addition, we discuss the idea that extreme running is not the
cause of sudden deaths during long marathons, but that undetected heart diseases are. This
literature review was written in hopes of making the community more aware of the dangers of
cardiovascular diseases, provide them with knowledge to reduce their risks, and encourage even
those with low risks to receive yearly checkups in the chances that they might have a genetic
disorder and are exacerbating their condition by putting too much stress on their hearts.
1.
"Cardiovascular Diseases (CVDs)." WHO. N.p., n.d. Web. 02 Dec. 2015.
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The Heart
The heart is an organ to be revered. Its
strength compared to its size is astounding. The heart
beats approximately 100,000 times a day with each
beat pushing blood 20 cm further through the vessels.
Where does this strength come from? The heart,
sometimes called a double pump, consists of four
small chambers (two atria and 2 ventricles) and 4
valves (2 atrioventricular valves and 2 semilunar
valves. As Figure 1 illustrates, the two atria sit above the ventricles, with atrioventricular valves
separating the two. All valves are made of simple squamous epithelial cells. The atrioventricular
valves have chordae tendineae anchoring them to the papillary muscles in the heart walls to
prevent the valves from opening backwards, or inverting. The right atrioventricular valve has
three leaf-like cusps and is thus called the
tricuspid valve while the left atrioventricular
valve has two cusps and is thus called the
bicuspid, or mitral, valve. The semilunar valves
separate the ventricles from the rest of the body.
Both have three cusps and do not have chordae
tendineae. Inversion is prevented based on
pressure differences as will be discussed below
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(see figure 2). The job of these valves is simply to allow blood to travel in one direction through
the heart.
As figure 3 depicts, when blood first enters the heart if flows in from the superior and
inferior vena cava into the right atrium. In order for the right atrioventricular valve, or tricuspid
valve, to open and allow blood to move to the right ventricle, the pressure in the right atrium
must exceed the pressure in the right ventricle. When this happens the cusps are forced to open
downward and the chordae tendineae are relaxed. Because most of this pressure comes from the
filling of the atria with blood, the atria do not need to generate much pressure by contracting.
Therefore, the muscle that makes up the
atria is thin compared to the ventricles.
Once most of the blood is in the right
ventricle and the ventricle begins to
contract, the pressure of the right
ventricle will be greater than the pressure
of the right atrium, causing the cusps to
come back together. The chordae
tendineae become tight and prevent the
valve from inverting or opening into the atrium. The function of this right pump is to take
deoxygenated blood that has come in through the veins and send it to be oxygenated to the lungs.
Thus, the semilunar valve that separates the right ventricle and the pulmonary arteries is called
the pulmonary valve.
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Once the red blood cells have oxygen bound to them, the blood must return to the heart
so that it can be effectively pumped through the body. As before, blood coming to the heart must
enter the atria. This time it goes into the left atrium through the pulmonary veins. When the left
atrium is filled with newly oxygenated blood, it’s pressure is higher than the pressure in the right
ventricle due to the amount of blood in the atrium, the cusps of the mitral valve to open
downward. Pressure starts to build in the left ventricle as it fills with blood and as its walls begin
to contract. First the pressure will rise above the pressure in the left atrium, shutting the mitral
valve, and then it will rise above the pressure in the aorta, causing the aortic valve to oven. The
aorta is the largest artery in our body and connects the heart to the vessels of the body. It will be
discussed in further detail in the next section.
Now that the structure of the heart and
how blood moves through it has been
discussed, it is crucial for this thesis to
understand how the heart works on the cellular
and molecular level. What is unique about the
heart is that it is auto-rhythmic; it contains
cells that can cause contraction without any
neural input. The main muscle cells are called
striated muscle because it looks striped. A cell
of the heart muscle, or a cardiac myocyte, is
made of myofibrils, long cords of protein, in its
cytoplasm. A myocyte’s cell membrane is called the
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sarcolemma and it is wrapped around the myofibrils. Its sarcoplasmic reticulum is analogous to
an endoplasmic reticulum of a non-muscle cell. Instead of synthesizing molecules, however, the
sarcoplasmic reticulum stores calcium ions and pumps them into the sarcoplasm when the
muscle is stimulated (See Figure 4). Myofibrils are made of units of sarcomeres, the basic
contractile unit. Sarcomeres are made up of regulatory proteins troponin and tropomyosin, as
well as the contractile proteins myosin and actin. When calcium ions are released from the
sarcoplasmic reticulum it binds to troponin which causes tropomyosin to move. This uncovers
the myosin binding sites on actin, allowing myosin heads to attach to those sites and physically
pull (See figure 5). This action causes contraction or shortening of the muscle. ATP is then
utilized to release myosin from actin, causing relaxation.
Myocytes and the content of their sarcoplasm are physically connected to each other
through intercalated discs. Intercalated discs are made up of two types of cell junctions. First
there are desmosomes which bind intermediate filaments of both cells and holds the cells
together so that separation does not occur during contraction. Secondly, there are gap junctions,
channels between two cells that connect their cytoplasm, allowing molecules and ions to easily
travel between the cells. These are important because it allows the electrical impulses to directly
pass from cell to cell. These channels are composed of two connexons, one in the membrane in
each cell that join together to create a channel.
Since the heart does not require
stimulation from nerves, the signal that
travel through gap junctions and causes
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the release of calcium is produced by pacemaker cells. Pacemaker cells are located in four areas
of heart. One group of these cells make up the sinoatrial node (SA node) because it is located on
the upper part of the wall of the right atrium, and the second is called the atrioventricular node
(AV node) because it is located in the right atrium, just above the interventricular septum. The
SA node is the main pacemaker of the heart. It fires at a rate of about 60-70 depolarizations/
minute when it spontaneously depolarizes and repolarizes, or the charge inside the cell becomes
more positive and then comes back down to normal. The change in voltage across the cell
membrane allows voltage gated channels to open and ions to flow through the membrane. This
electrical charge spreads from one cell to the next through intercalated discs, eventually covering
both atria. The calcium that is released due to this stimulus causes the atrial myocardium to
contract. The signal from the SA node also spreads through the atria then reaches the AV node.
There is about a 100 microsecond delay at the AV node before it fires and the signal is spread
through the ventricles. Its purpose is to allow enough time for the atria to contract and the
ventricles to fill with blood before the ventricles contract. When the AV node depolarizes the
signal not only travels through the ventricle walls but also down the Bundle of His and purkinje
fibers which are located along the septal wall and the apex of the heart, respectively (see figure
6). It travels faster through these structures so that the signal can reach the bottom of the
ventricles faster and allow the ventricles to contract as a unit.
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There are many
graphs and charts that
help clarify what is going
on in the heart in terms
of electrical activity,
pressure, volumes and
sounds.
Electrocardiograms
(ECG) show the
electrical activity of our
hearts. This representation is one often seen in doctors’ offices. The reason is because if we can
identify a problem with electrical conductance, we know that there probably is a mechanical
problem that follows it. ECGs are possible because the electrical signals in our heart can reach
the surface of our body where it can be measured with electrodes placed on our skin. If put in the
proper position around the chest, one of the signals will look similar to that represented in figure
7. Waves are labeled as P, QRS, or T, and represent the depolarization or repolarization of
myocardium. Starting at the left end and moving right, the P wave represents the depolarization
of the atria, the QRS complex represents the depolarization of the ventricles, and the T wave
represents ventricular repolarization. The repolarization of the atria is masked by the QRS
complex. An ECG strip is printed on a grid with small boxes that are 1 mm in length that add up
to a large box 5 mm in length. Machines are programed to print out ECG strips so that the length
of each 1 mm box represents .04 seconds and its height represents .1 mV. This allows us be sure
our heart is depolarizing and repolarizing enough and at the proper time.
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An additional
method of looking at the
activities of the heart is
through a Wiggers
Diagram (See figure 8).
This graph plots the
ECG as well as
pressures, heart sounds
and the volume of the
left ventricle as a
function of time on one
diagram. Therefore, we know that following ventricular depolarization (QRS complex) the mitral
valve closes and the pressure begins to rise. The pressure in the left atrium and ventricle
increases once the mitral valve closes because the left ventricle is contracting. The sound that is
generated when the AV valve closes is not from the valve itself but from the vibrations within
the walls of the ventricles that it causes (Cohen, Zoe. “Heart Sounds”, n.d.). It is the “lub” in the
“lub-dup” we hear when listening to our hearts. The “dup” comes from the vibrations in the wall
from the semilunar valves closing. The other sounds indicated in the Wigger’s Diagram are
sometimes pathological and will be talked about later. Looking at the ventricular volume line,
there is a constant volume after AV valve closure and before aortic valve opening even though
there is an increase in pressure due to contraction. This is called isovolumetric contraction. All
valves are closed because the pressure has yet to surpass the pressure in the aorta, preventing
blood flow out of the ventricle. Once the semilunar valves open there is a decrease in volume in
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the ventricles as blood leaves. The pressure in the ventricles decreases when blood is ejected,
causing the pulmonary valves to close. As the ventricle walls continue to relax there is
isovolumic relaxation because no valves are open and no blood is entering or leaving the
ventricles. When the pressure in the ventricles is lower than that of the atria there is an increase
in volume because the AV valves open and allow the ventricle to be filled with blood once again.
The filling of the ventricles is a passive process until the “atrial kick” at the very end. This is
atrial contraction and is responsible for about 10% of the final diastolic volume at rest.
The Vessels
Blood vessels are the highways that transport oxygen saturated red blood cells to
every cell of our body. The four main types of vessels are arteries, arterioles, capillaries and
veins. This thesis will explore their makeup and function, and then discuss how these vessels are
kept healthy.
When oxygenated blood first leaves the left
side of the heart it enters the aorta, the largest
artery of the body with a diameter of about three
centimeters (O’Gara, 2016) and wall thickness of 2
mm (Cohen, Zoe. “Arteries and Arterioles”, n.d.).
The aorta is
thick and
highly elastic.
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From the aortic valve it arches up before it dips back down and runs along the abdomenal wall. It
can be seen in figure 9 that when the descending aorta reaches our pelvis the aorta splits into the
left and right common iliac arteries which run down each of our legs. There are several hundred
arteries that branch off of the aorta that supply the head, limbs and organs. These arteries have
walls that are about 1 mm thick and are highly elastic. They are specialized to serve as rapid
transit passageways and they act as a pressure reservoir that helps maintain blood flow. Artery
and arteriole walls have the same general make up that is shown in figure 10. There is a layer of
smooth muscle and elastic fibers called the tunica media. The tunica media is lined with the
tunica intima, endothelium along the lumen of all vessels, and the tunica adventitia which is
made of collagen fibers.
Arteries then branch into arterioles, of which there are about half a million of. They not
only have thinner walls but the walls are much more muscular and less elastic than arteries.
Arterioles supply individual organs and can adjust how much blood goes to each when the
smooth muscle around the vessels contract or relax. This smooth muscle is innervated by
sympathetic nerve fibers and is sensitive to many local chemicals and hormones which cause its
contraction or relaxation. For instance, if there is more myogenic activity, an increase in oxygen,
a decrease in carbon dioxide, an increase in endothelin, sympathetic stimulation or cold,
vasoconstriction will occur. The radius of the
arteries decreases, increasing resistance and
decreasing the flow rate. When the smooth
muscle relaxes this is termed vasodilation and
there is an increase of blood flow to the tissues.
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Vasodilation is cause by factors opposite of those that cause vasoconstriction. An increase in
endothelial-derived relaxing factors (EDRF) such as nitric oxide, increased histamine, increased
H+, increased potassium, increased osmolality, and adenosine release and prostaglandin release
will also cause vasodilation. The one place we don’t want vasoconstriction is the brain so
sympathetic innervation is missing on the arterioles of the brain (Cohen, Zoe. “Arteries and
Arterioles”, n.d.). The ability to shunt blood to areas that need it the most is crucial. Areas
require more blood if there is an infection, hence why histamine release produces dilation, or if
there is more metabolic activity in a certain tissue or organ, which is why increased carbon
dioxide and decreased oxygen also stimulate vasodilation.
Arterioles drain blood into capillaries. An average person will have about 10 billion
capillaries in his or her body. The walls of capillaries are only a cell thick and are only covered
by a thin basement membrane, making it easy for substances to cross from these vessels into the
surrounding tissue. They are also so small in diameter that only one red blood cell can move
through at a time. These factors, combined with the incredibly slow rate of blood movement in
capillaries, allow for the exchange of oxygen and nutrients from the blood with carbon dioxide
and wastes from the tissues. Capillaries are the site of more than just gas exchange however.
White blood cells can squeeze between the cells of the capillaries, large molecules and protein
can often leave the circulation through fenestrations or pores in the basement membrane, and
filtration and reabsorption of liquids occur due to pressure differences. There are two main types
of pressures that exist: hydrostatic pressure and colloid osmotic pressure as shown in figure 11.
Hydrostatic pressure is pressure exerted by fluid. On the arterial end of capillaries there is much
higher hydrostatic pressure in the capillary than there is from fluid in the tissue, causing
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filtration. Colloid osmotic pressure, also called oncotic pressure, is a sort of sucking pressure
caused by protein. It is mainly caused by albumin in the blood, the most abundant protein in our
blood. Since there is a higher concentration of albumin in the capillary this oncotic pressure pulls
fluid from the tissues into the capillaries, causing reabsorption. The role of these two forces on
fluid movement across the capillary membrane is described by starling’s principle.
Similar to arteries, there are several hundred veins. Their walls are half as thick and they
don’t have much muscle, making them highly distensible or compliant. Because veins do not
contain much smooth muscle or elastic fibers, blood pools in the veins. At any given time 60%
of our blood resides in veins because they are so compliant. When innervated by sympathetic
stimulation the veins become more toned, which helps increase the return of blood to the heart.
Unlike arteries, veins contain valves similar to the semilunar valves of the heart to keep blood
flowing in one direction. All veins from the head drain into the superior venae cavae and all
veins from the rest of the body drain into the inferior venae cavae. Both the superior and inferior
vena cavae then flow into the right atrium and the cycle begins again. Besides sympathetic
activity, the negative pressure in the right atrium after blood has drained into the right ventricle
creates a sucking pressure, increasing blood flow back to the heart. Skeletal muscle activity is
also useful because as this muscle contracts it squeezes the veins that lie within it, and therefore
blood moves towards the right atrium. Breathing causes a similar effect. When the diaphragm
contracts it pulls down, creating more space in the thorac. With a greater volume but the same
amount of air molecules, pressure decreases. This is what causes the lungs to expand but is also
what causes blood to move towards the heart which is located in this thoracic space because
liquids move from high pressure to low pressures.
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Blood vessels are not just handy for transportation; they permit indirect evaluation of the
cardiovascular system and other systems of the body through the use of measurements such as
blood pressure. Blood pressure is the force exerted by the blood against a vessel’s wall, therefore
it depends on the volume of the blood and how compliant the walls of the vessels are. Blood
pressure is measured using a sphygmomanometer. This will give a reading of the maximum
pressure in arteries, or the systolic pressure, over the minimum pressure in the arteries, or
diastolic pressure. The average systolic/diastolic pressure is 120/80 mmHg. The reason we can
feel a pulse is because this pressure difference exists, even though there is a constant blood flow
through the vessels. The difference between systolic and diastolic pressure creates a pressure
wave. This wave is created by the heart during systole and originates in the ascending aorta
because it is such an elastic and compliant artery (Cohen, Zoe. “High Blood…”, n.d.). Therefore,
we can only feel a pulse in arteries, especially those of younger people’s, because of their
compliance and elasticity. As the wave travels from the aorta it amplifies so a pulse might be felt
better in the limbs. Baroreceptors, renin-angiotension system (RAS) and aldosterone are three
systems that help maintain a healthy blood pressure (Cohen, Zoe. “High Blood…”, n.d.).
Baroreceptors are sensors that sense the blood pressure and send that information to the
brain. They allow for quick and short lived regulation. The main baroreceptors are located in the
carotid sinus, arteries that flow along either side of our neck up to the brain, and in the aortic
arch. The baroreceptors in the carotid sinus send information to the brain through cranial nerve
#9 and the baroreceptor in the aortic arch through cranial nerve #10 (Cohen, Zoe. “High
Blood…”, n.d.). Baroreceptors communicate by the speed they fire at. If blood pressure is too
high, they fire more rapidly which tells the brain to decrease sympathetic and increase
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parasympathetic activity. This might cause a decrease in heart rate (how fast the heart pumps
blood), a decrease in stroke volume (the amount of blood ejected out of the left ventricle per
beat) and an increase in vasodilation.
For a longer lastinh change in blood pressure, the body would make adjustments to the
renin-angiotensin system (RAS) as well as the aldosterone level. The RAS is a hormone system
that usually results in the increase in blood pressure by inducing the retention of salt (Na+ and
Cl-) and the excretion of potassium. Since water always follows salt, more water in our vascular
system would contribute to an increase in blood pressure due to an increase in blood volume.
The RAS also supports the release of aldosterone which also causes the retention of water
through salt reabsorption in the kidneys, the increase in sympathetic activity, and
vasoconstriction, and the release of antidiuretic hormone (ADH) from the pituitary gland. ADH
increases the absorption of water and decreases the excretion of fluid in the collecting ducts of
the kidneys (Cohen, Zoe. “High Blood…”, n.d.).
Blood
Women have about 5 liters of blood in their system, men about 5.5 liters. Blood is
composed of 55% of plasma, 45% red blood cells and less than 1% are platelets and white blood
cells.
Plasma it-self is 90% water. Not only does this high percentage of water absorb and
distribute heat generated during metabolism, but it also acts as a transport medium for substances
in the cardiovascular system. Plasma holds many non-cellular, organic and inorganic
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constituents. Six to eight percent of our plasma is composed of proteins such as albumins,
globulins, and fibrinogen while 1% are inorganic constituents such as sodium, chloride,
potassium, calcium, and bicarbonate. As discussed earlier, the proteins in plasma help establish
an osmotic gradient between blood and interstitial fluid at the capillary level which influences
filtration and reabsorption and inversely nutrient and waste exchange. Protein is also the
substance that buffers our blood and maintains the pH. Albumin is the most abundant protein
within plasma and as such is responsible for most of these effects. It is also useful because it can
bind bilirubin, bile salts and penicillin. Globulins are proteins with many functions. Some
globulins are used as clotting protein while others are associated with immunity. Fibrinogen, too,
is an important protein needed for clotting to occur.
Red blood cells, also known as erythrocytes, are derived from red bone marrow where
they mature, lose their nucleus, and are sent out to the blood stream. The loss of a nucleus is
advantageous because it gives the erythrocyte a flat, disc shape that is indented in the middle.
This makes the cell thin and flexible which will
be needed when traveling through tight spaces
such as capillaries. It also allows for a larger
surface area which is needed when traveling
along pulmonary capillaries where oxygen and
carbon dioxide exchange occurs. Erythrocytes
also do not have any mitochondria because
their main job is to transport oxygen to the
tissues and carbon dioxide to the lungs and we
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do not want those cells to metabolize the oxygen. Each red blood cell has about 250 million
hemoglobin molecules, each of which contain four iron groups that bind one O2 molecule each.
This means that each red blood cell can carry about a billion molecules of oxygen at a given
time. How does a red blood cell know when to pick up oxygen and when to release it? It has to
do with its affinity with oxygen. Hemoglobin’s affinity for oxygen is affected by the partial
pressure of oxygen and carbon dioxide in a local area. The hemoglobin saturation curve
summarizes this nicely (See figure 12). The curve shifts to the left when the pH of blood
increases, the partial pressure of carbon dioxide decreases or when temperature decreases. All
these conditions point to an increased affinity of hemoglobin for oxygen, leading to binding of
oxygen to red blood cells. The opposite is also true; more acidic conditions, high CO2 pressure
and high temperature lead to decreased affinity for oxygen causing oxygen release.
A healthy red blood cell circulates the system for about four months (110 to 120 days)
before it is taken out of circulation and removed by cells in the spleen. Red blood cells undergo
hemolysis if they are damaged and are destroyed before 100 days of circulation (Schrier, 2015).
More erythrocytes are created to either replace old red blood cells or increase the amount of red
blood cells there are in the system. The later would be necessary if a person experiences an
increase in altitude. At higher altitudes less oxygen is available in the air (low partial pressure of
oxygen). This low oxygen is detected by the kidneys which increases the concentration of
erythropoietin in the blood. Erythropoietin is a hormone that is used to signal the bone marrow to
increase the rate of production of red blood cells. This increase in red blood cells allows for more
oxygen to be bound and transported to the body, even though there are low levels of oxygen in
the air.
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White blood cells are nucleated cells used as our defense system. They include the
granulocytes (neutrophils, basophils, and eosinophils) and the agranulocytes (monocytes and
lymphocytes). The term granulocytes is used to describe cells that contain granules in its
cytoplasm. These granules can sometimes be used to destroy other cells or particles when
released. Granulocytes and agranulocytes can be easily distinguished when the cells are dyed and
viewed under a microscope because the granules often stain well.
Neutrophils are phagocytes which means they are able to engulf bacteria and small
objects into their cytoplasm and then destroy them. Eosinophils are capable of destroying
parasites but are also responsible for allergies when they recognize an object such as a certain
food, as a pathogen and create an immune response towards it. Monocytes also become
phagocytes They are then called macrophages and can leave the blood circulation. Lymphocytes
are cells that are specialized to recognize foreign invaders, or antigens, and destroy them by
multiple different methods. Depending on the type of lymphocytic cell, it might call in
phagocytes or destroy the antigen itself using its specialized proteins. Basophils are sparse in the
blood yet they are the largest. They too can act as phagocytes and produce inflammatory
reactions during immune responses by releasing histamine and serotonin.
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Coronary Artery Disease
Coronary artery disease
(CAD) develops when the
coronary arteries, the arteries
that supply the heart muscle
with oxygen and nutrients,
become damaged or diseased
because of plaque deposits or
inflammation. Plaque buildup
causes damage to heart tissue
because it limits the amount of blood flow to area. The tissue then becomes ischemic and unable
to contract. If damage is due to plaque deposits as in figure 13, it is termed atherosclerotic
cardiovascular disease. The World Health Organization (WHO) estimates there will be about 20
million CVD deaths in 2015. Researchers project that CVD alone will be responsible for more
deaths in low income countries than infectious diseases by 2030. Coronary heart disease is most
notable in Eastern European and former Soviet countries, where mortality rates have continued
to increase at an alarming pace and where the highest mortality rates ever recorded are currently
being observed. By contrast, CHD mortality rates in Japan and Several European Mediterranean
countries have remained relatively low (Institute of Medicine, 2010). 610,000 die of heart
disease, 370,000 people die annually from CHD (U.S. Department of Health & Human Services,
2015). Risk factors for CAD can be categorized as modifiable or non-modifiable. Non-
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modifiable means risks that are out of one’s control. One non modifiable risk factor for CHD is
gender. Middle- aged males are 2-5 times more likely to have CHD than women of the same age.
However, in both sexes, the risk of CHD increases with age. This, combined with the nonmodifiable risk factor of being a woman after menopause, causes the sex difference in risk factor
levels to diminishes with increasing age. One-third of the age- related increase in CHD risk in
men and 50-60% in women is explained by the difference in serum total cholesterol level, blood
pressure, body mass index, and diabetes prevalence. (Jousilahti, 1998) The post menopause risk
factor in woman is partially also explained by the difference in blood pressure, pulse rate, serum
total cholesterol, triglycerides, low- density lipoprotein cholesterol between pre and post
menopause (Bulliyya, 2001). Lastly, family history of CHD can be a large non- modifiable risk
factor. Genetics can affect lipoprotein metabolism, homeostasis of blood pressure, glucose
metabolism, hemostasis, inflammation response genes oxidation mediators, adhesion mediators,
and gene regulatory factors which can lead to CHD (International Task Force for Prevention of
Coronary Heart Disease, n.d.).
Modifiable risk factors
can be prevented and include
dyslipidemia, diabetes,
hypertension, and smoking.
Dyslipidemia means there is an
abnormal amount of
lipoproteins (lipids,
phospholipids, cholesterol, and
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triglycerides that are carried by protein) in the plasma. Total blood cholesterol levels that are 240
mg/dL or above, HDL levels that are 50 mg/dL or below, LDL levels that are 160 mg/dL and
above, and triglyceride levels that are 200 mg/dL and above are considered a risk (see figure 14).
LDL delivers cholesterol to the tissues which is why high levels of it is a risk for CAD while
HDL reverses cholesterol transport. It picks up cholesterol from the tissues and returns it to the
liver for metabolism. Thus, high levels of HDL are protective against CAD. Diabetics can have
the same risk factors of CAD because it often involves dyslipidemia, obesity and a sedentary
lifestyle. Diabetes is associated with a two-fold increase in the risk for CAD death and up to a
six-fold risk for stroke.
Hypertension, or high blood pressure,
means that with each beat arteries must deal with
greater pressure than normal, which mean the
heart must now work harder. Over time, this leads
to hypertrophy of heart muscle and stiffer arteries.
These injured arteries can attract more LDL
cholesterol and white blood cells and build up,
reducing blood flow to the heart. The plaque can
also rupture and travel along arteries until it
becomes stuck in a vessel. An obstruction in a vessel such as this will cut off blood flow which
results in a heart attack (“Atherosclerosis”, n.d.). The chart in figure 15 is a perfect guide for
levels of blood pressure readings. Smoking is another modifiable risk factor because it too can
cause damage to your heart and vessels, leading to coronary heart disease. Nicotine in cigarettes
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increases heart rate. The heart must work harder, causing an increased blood pressure and an
increased afterload. Smoking also increases free fatty acids in the blood, leading to dyslipidemia.
Lastly, it increases carbon dioxide levels in the blood so that there is competition with oxygen
binding to hemoglobin. Studies indicate that 21% of the annual mortality from CAD is traceable
to cigarette smoking, and this also includes second hand smoke. After smoking is discontinued,
the risk associated with CAD may decrease as much as 50% in one year (Cohen, Zoe. “Coronary
Artery Disease, n.d.).
Dyslipidemia, diabetes, hypertension and smoking are considered modifiable risk factors
because smoking can be stopped, one can eat less fats, take medication to control lipids, and
hypertension, or exercise to reduce these risks. These actions are most effective if done while
lipids and hypertension are borderline high, but not considered high yet.
If blood flow through the coronary arteries is blocked by at least 50% it leads to
myocardial ischemia (inadequate blood supply). As dangerous as this is alone, it can be deadly
when paired with increased cellular metabolism which is seen during exercise. The tissue is
using oxygen at a greater rate during increased cellular metabolism but the ischemic heart cannot
meet this demand for oxygen. Myocardial ischemia can also be a product of a coronary spasm,
hypotension, arrhythmias, and decreased oxygen carrying capacity of the blood.
The oxygen carrying capacity of the blood decreases during hypoxemia (lack of oxygen),
or anemia. There are many different type and causes of anemia. Causes include impaired red
blood cell production, blood loss, or increased red blood cell destruction. Impaired red blood
cells may have an abnormal shape, an abnormal color, or both. If the cells are larger than normal
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they are considered macrocytic, if smaller than normal microcytic and if they are normal
normocytic. The color of red blood cells is important because it represents the concentration of
hemoglobin it contains. Recall that hemoglobin has a molecule of iron in it. This gives red blood
cells its color. If red blood cells contain too little hemoglobin it is termed hypochromic, if too
much red blood cells hyperchromic, and if it contains a normal amount of hemoglobin red blood
cells are said to be normochromic. The most common form of anemia is due to iron- deficiency.
Iron deficiency can result from too much bleeding such as GI bleeding in men or excess bleeding
during menstruation and pregnancy in women, or iron-deficiency can result from dietary factors.
Other types of anemia are due to hemorrhaging, sickle-cells (stiff red blood cells that can’t hold
oxygen properly), hemolytic red blood cells (cells that are destroyed too early), and folate
deficiency (folate is needed for red blood cell production).
Myocardial cells become ischemic within 10 seconds of no oxygen supply. After several
minutes the ischemic tissue becomes damaged and the heart can no longer contract. Cardiac
output decreases and the heart is no longer able to meet the demands of the body or its own
tissue. If ischemia is detected it can be treated with nitrates which cause vascular dilation, betablockers which decrease heart rate and thus reduce cardiac muscle demand, decreasing calcium
which would also slow down heart rate and allow for greater coronary filling time, percutaneous
coronary intervention which dilates the coronary vessels with a catheter, or coronary artery
bypass graft which creates a new passage way for oxygenated blood to travel directly
downstream of the blocked. Cardiac tissue is viable only for 20 minutes under ischemic
conditions. If it is left untreated myocardial infarction could occur. This is the leading cause of
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death in the US. Myocardial infarctions can either involve the full thickness of the ventricles
(this is more common) or only 1/3-1/2 of the ventricular wall.
Running
An important question to answer is “Is running a natural thing for humans or does it
cause more harm than good?” To answer this question, we must look at our evolution and
determine whether our body was built for these conditions. Humans are thought to have evolved
from apelike ancestors who are not considered excellent runners. For examples, though
Chimpanzees can spring, it’s normally only for distances less than 100 m (Lieberman, 2007). In
fact, mammals in general are not considered to be excellent runners. You might be thinking
“well that can’t be true, dogs and horses can outrun me in distance and in speed.” While humans
were not built for speed, Lieberman’s and Bramble’s paper on The Evolution of Marathon
Running discusses how humans were built to handle the energetics, stabilization and
thermoregulation required by endurance running.
Humans evolved the ability to walk on two legs, a trait known as bipedalism, over 4
million years ago (National Museum of Natural History, 2016), but just because we have the
ability to walk does not mean we are built for running. Humans became good runners about 2
million years ago, long after bipedal walking and around the same time that humans ingrained
meat into their diet (Lieberman, 2007). The weapons at this time only allowed them to kill
animals from short distances away. The dangers of this and having to compete with other
carnivores lead to the evolution of human traits which made humans better runners. They could
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now use strategies such as persistence hunting where a runner follows an animal for hours until
the animal develops hyperthermia, and is then safe to kill from short distances.
In terms of energetics, endurance running is only 30-40% more costly than efficient
walking speeds and humans have elastic energy stored in tendons which, when recoiling, push
the body forward (Lieberman, 2007). Human are actually considered to be more stable when
running than walking. We have an enlarged gluteus maximus which contracts more during
running than walking, a narrow waist, a mobile thorax that allows rotation of the arms and trunk,
and enlarged semicircular canals in the ears that improve the sensitivity of the vestibule-ocular
reflexes to rapid pitching movements generated in running but not walking (Lieberman, 2007).
Most importantly, humans evolved to having less body
fur and more sweat glands, making us more efficient at
cooling our core body temperature than any other
mammal. Because of this, humans can even outrun
horses and dogs in long distance runs. Another
important point to consider is the strength of our bone.
Running produces much more stress on the skeletal
system than walking as seen in figure 15, so humans had to evolve ways to minimize this stress.
One way of reducing this stress is to increase the surface area in joints so that the force is spread
over larger areas. It was found that Homo had an enlargement of most joints of the lower body
including the femoral head and knee, the sacroiliac joint, and the lumbar centra (Bramble, 2004).
There is also enlargement of the iliac pillar in the pelvis and a larger cross- sectional area of the
calcaneal tuber (Bramble, 2004). Additionally, we have a shorter femoral neck, which is thought
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to reduce bending moments in the femoral neck, and a reduction in hip breadth, which also
reduced bending moments on the pelvis and lower back (Bramble, 2004).
Though humans no longer need to hunt our food, these evolutionary trademarks are still
there and suggest that not only is running safe, but it could be beneficial. Though this doesn’t
necessarily mean we have been built for extreme marathon runs. As Lieberman and Ramble
state, “In short, the human ability to run long distances, such as a marathon, is neither a simple
byproduct of the ability to walk bipedally, nor a biologically aberrant behavior. Instead, running
has deep evolutionary roots. Although humans no longer need to run, the capacity and proclivity
to run marathons is the modern manifestation of a uniquely human trait that helps make humans
the way we are” (Lieberman, 2007).
Running and the Heart
This thesis has explored how evolution has given humans an ability to run and do it
safely through protections of bones, core body temperature, energy and even ability to safely run
without falling. Running long distances often has profound effects, particularly to the
cardiovascular system. Most sudden death that occur during long runs are said to be
cardiovascular related so this thesis will look at what endurance running over time does to one’s
heart and whether this is dangerous or not.
The name marathon comes from to Battle of Marathon from which a herald,
Pheidippides, ran from Marathon to Athens, a distance of 26 miles, to announce the Greek
victory. Shortly after, he collapsed and died from exhaustion. This is not unheard of as in 2009,
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seven deaths occurred in a six-week period during half and full marathons and in a nine-year
study it was found that 28 people in 3,718,336 full marathon runners died either during or within
24 hours of finishing a marathon race, with the average age of those that died being 45 years.
While that might not seem like a lot from a statistical point of view it was a big impact to the
families and community who previously though running was extremely safe. At first it was
thought this increase in deaths was occurring because there was a large jump in marathon
participants, meaning these new athletes were less experienced and perhaps did less premarathon training. Those that train less for a marathon were found to have more cardiac injury
biomarkers after a marathon. However, it was found that these runners finished the marathon
with an excellent time. Next, experts looked at physiology to see what was happening. Although
there was a 90% change of injury amongst those training for a marathon, the majority of this was
musculoskeletal. Sudden deaths were cardiac and cardiovascular related. These deaths included
such things as coronary atherosclerosis, cardiac arrhythmias, prolapsed mitral valves,
hypertrophic cardiomyopathies, coronary fibromuscular dysplasia, and heart failures. Some may
read this and think this is a reason to stop running marathons or push oneself too much during
workouts, or at the very least get a screening for any cardiac risks but on the contrary, this study
found that the risk of dying in a marathon remains low. In addition, many other studies were
observing the tremendous amount of benefit from aerobic exercise.
Physical movement alone causes an increase in our metabolic activity. This is because
more muscles are contracting and at a higher frequency, thus more ATP is needed to release the
cross bridges between the myosin heads and the actin filaments. In order to make more ATP,
more oxygen must be brought in by our vascular system and CO2 carried out. This could mean
29
that the heart pumps faster or that with each pump more oxygenated blood is released in the
systemic circulation. Prior to exercise the heart begins to beat faster as one anticipates exercise.
This is called an anticipatory response. Once exercise starts, stroke volume may increase up to
40-60% of maximal capacity before it plateaus. An increased stroke volume during exercise is
essential for maintaining cardiac output because the increased heart rate alone could cause a
decrease in diastolic filling time. In metabolically active tissues we get vasodilation of the
arterioles, meaning vascular resistance decreases so that more oxygenated blood can reach these
muscles. As a result of increased heart rate and stroke volume, cardiac output increases
proportionally with exercise intensity and can increase as high as 20-40 L/min. All of this newly
oxygenated blood mainly goes to tissues with the greatest demand or metabolic activity such as
skeletal muscles and the heart.
With continued training we start to see physical changes to the heart. Its mass increases
because its walls become thicker from pumping more forcefully at a faster rate. The volume of
its chambers also increases because of the increased blood volume returning to the heart and
increased stroke volumes. This increase in mass and volume is termed hypertrophy. Because of
these physical changes of the heart, trained athletes have increased stroke volumes even at rest,
not to mention during exercise when compared to an untrained individual’s stroke volume during
exercise. At rest an untrained individual might eject 50 mL/beat while a world-class endurance
athlete 110 ml/ beat (Cohen, Zoe. “Integration”, n.d.). This increase in stroke volume is due to a
few factors. First, with skeletal muscles flexing more it causes an increased pressure on veins
which in turn causes an increase in blood volume returning to the heart. The increase in atrial
inotropy, or contraction strength, and an increase in ventricular relaxation cause an increased
30
filling of the ventricles. An increase in inotropy of the ventricles decreases end systolic volume
and thus increases stroke volume and ejection fraction. The trained individual will have a higher
cardiac output and whole body oxygen consumption during maximum exercise. They also have
an increase in blood volume, which is mainly due to an increase in plasma and a greater
production of red blood cells. This increased blood volume causes a greater opening of existing
capillaries and even an increased number of capillaries, also increasing the blood supply to
skeletal muscles. Lastly, the blood pressure of athletes is quite low during rest and submaximal
exercise despite the fact that there is an increased blood volume because there is better
compliance of vasculature.
From Couch to 5K
The Center for Disease Control National Institutes of Health, and many other sources
realize the importance of daily exercise and therefore provide guidelines and basic information
that everyone should know. The following exercise recommendations emerged from
epidemiologic studies, in which the relation of exercise to health outcome is evaluated, and
exercise training studies in a controlled laboratory environment. It is important to instill habits of
health in children and prevent certain diseases such as childhood obesity and diabetes. The CDC
recommends children participate an hour or more in aerobic activities each day (Physical, 2012).
This should involve vigorous-intensity activities such as running at least 3 days per week. They
should participate in muscle strengthening exercises and bone strengthening activities, such as
jump rope or running, at least 3 days a week each. Age appropriate muscle strengthening activity
31
includes things such as doing gymnastics, playing on a jungle gym or climbing trees. The NIH
highly suggests that these activities remain varied.
Adults need at least 2 hours and 30 minutes of moderate-intensity aerobic activity a week
or this can be supplemented by an hour and 15 minutes of vigorous-intensity aerobic activity a
week. In addition, they need to complete muscle- strengthening activities at least two days a
week on all major muscle groups. This is important for all adults over the age of 18 (Physical,
2012). Though you could split this time up the CDC recommends doing at least 10 minutes of
moderate or vigorous effort activity at a time. However, it is important to keep in mind that these
are the minimal requirements and that more time equals more health benefits. As adults get older
they should attempt to increasing their aerobic activity to 5 hours of moderate exercise a week or
2.5 hours of vigorous- intensity aerobic activity. The NIH suggests that inactive adults gradually
increase their level of activity as well (Recommendations, 2015). The reason for this was that a
study done by the American College of Sports Medicine along with other studies found that
higher intensity exercise produced greater gains in fitness (Mathews, 2012). Adults over the age
of 65 should be physically active for at least an hour and a half a week, though experts suggest
that those with a chronic condition such as heart disease, should ask their doctor about what
types and amounts of activity are safe for them.
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Appendix
Appendix A
Festival of Books
I created the following pamphlet for the Festival of Books. Most people were interested
in basic information on the heart so I would explain the chambers, the valves, the flow of
blood, and give pedestrians some interesting facts about the heart overall. People
absolutely enjoyed the models of the heart and getting to take them apart. A lot of the
older folks asked us questions based on their experience as with heart disease. For
instance, a couple came up to us and shared that the wife’s dad was about to undergo
mitral valve replacement. They asked us what the mitral valve was, how the procedure is
done, what they can expect, and so on. It was a very unique and priceless experiences as
it gave me a glimpse of how I could one day explain the physiology and pathophysiology
to my own patients. I also really enjoyed talking to younger kids about the dangers of
eating fatty foods and living a sedentary lifestyle. I’m confident that each person that
walked to our table learned something new about the heart and I could only hope they
realize from my pamphlet the high risks of heart disease from living a lifestyle that
popular in the American culture, and the wide benefits available from running.
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37
Appendix B
Poster Session