Last week we studied vertebrate and invertebrate systems with an examination of

musculoskeletal systems. This week we will investigate how animals transport

solutes and exchange gases within their bodies via the circulatory and respiratory
systems. This figure is an image of a heart using angiography with contrast dye so
that we can visualize the blood vessels (shown in red).

1
If an organism is capable of obtaining its necessary nutrients and removing its
metabolic wastes via diffusion, then it may be capable of surviving without a
circulatory system. In the more ancient invertebrate phyla such as the Porifera
(sponges) and Cnidaria (jellies and hydroids), this is the case and there is no
circulatory system.

Circulatory systems are needed by many multicellular organisms so that they are
able to deliver nutrients to the cells deep within the body and to remove metabolic
wastes produced by these cells. Circulatory systems usually have three major
components. These are:
1. A heart used to keep the blood circulating.
2. Blood, a liquid used to transport nutrients and waste products.
3. Blood Vessels, which are tubes used to conduct the blood throughout the body.
There are two basic types of circulatory systems:

Open circulatory systems (figure a) are the simplest type of circulatory systems.
These are found in many of the invertebrate organisms such as snails, clams, crabs,
arthropods and some molluscs. Seen in the left figure above, they have one or more
simple hearts with associated heart valves, a network of blood vessels, and a large
open space called a hemocoel. When the hearts contract, fluid pressure forces the
heart valves closed and the fluid hemolymph is forced out the vessels into the
hemocoel. When the hearts relax, the heart valves open and hemolymph is drawn

2
back into the heart, so that the cycle may repeat itself.

In open circulatory systems nutrients and wastes are exchanged by diffusion between the
hemolymph and body cells. This type of circulation is metabolically inexpensive, and as an
animal’s activity increases, the circulation becomes more efficient. One basic limitation is
that hemolymph cannot be selectively delivered to different tissues.
Closed circulatory systems (figure b) can be seen in all vertebrates and in some
invertebrate organisms such as the cephalopods, and earthworms (like the figure on the
right, above). In these systems, blood is confined to the heart and a continuous series of blood
vessels. Advantages of closed circulatory systems include:
• the need for less circulating fluid,
• high fluid pressure,
• more rapid blood flow, and
• more efficient transport of dissolved substances.
In closed circulatory systems, blood (the circulatory fluid) remains within discrete vessels for
distribution. The blood and interstitial fluid are physically separated, and as a result they
differ in their chemical compositions. Larger, more active animals need a higher pressure to
pump blood to all body cells. Some animals have a closed circulatory system composed of a
single circuit, while others have double circulation.

Typical features of closed circulatory system includes one or more contractile hearts, solutes
are exchanged with the environment and the body cells, they often contain disease-fighting
cells and molecules, they can be adjusted to match the animal’s metabolic demands, they
have the capacity to heal themselves when wounded , and the system grows in size as an
animal grows. Other advantages of a closed circulatory system are that nearly all body cells
are within one or two cell widths of a blood vessels, and that blood flow can be selectively
controlled with vasodilation/vasoconstriction of blood vessels.

2
The closed circulatory system of the vertebrates has the following functions:
1. Transports oxygen from gills or lungs to the tissues, and carbon dioxide from
the tissues to the lungs/gills.
2. Moves nutrients from the digestive system to all the body cells.
3. Carries waste products to the liver for detoxification and the kidney for
excretion.
4. Distributes the chemical messengers called hormones from their organ of
secretion, to the target at which they have their effect.
5. Act to regulate body temperature, by adjusting blood flow.
6. Promotes healing of wounds, and prevents blood loss through the creation of
clots.
7. Protects the body from foreign invaders by circulating cells and products (i.e.
antibodies) of the immune system.

3
In this portion of the lecture, we will examine the evolution of the heart with an
examination of the types of hearts that exist and then focus on the human heart, its
internal conduction system and a look at blood pressure, which the heart is
responsible to generate.

4
Fish were the first vertebrate to develop a heart. Their hearts have two chambers, as
seen here, and include a single atrium, and a single ventricle. Fish have one
circulatory path (i.e., single circulation). Atria are the receiving chambers of the
heart that produce minor contractions which move blood through one way valves
into the ventricles. The ventricles are the chambers which create contractions that
generate the major force responsible for maintaining blood pressure and moves the
blood. There are three valves in the two-chambered heart. These are “one-way
valves” that allow blood to flow only in a single direction. The first is found
between the veins that deliver blood to the heart, and the atrium. The second is
located between the atrium and the ventricle. The third is located between the
ventricle and artery that leaves the heart.
Contractions in the atria and ventricle are sequential and the following events take
place during the cardiac cycle of the two chambered heart:
1. At the beginning of the cardiac cycle, only the valve between the vein and atria is
open. During this time, the atrium fills with blood.
2. Upon filling, the atria contracts. This causes the first valve (at the vein) to close,
and causes the second valve, (i.e. between the atrium and ventricle) to open. At this
time, blood flows from the atrium, into the ventricle.
3. Next, the atrium relaxes, and the ventricle contracts. This causes closure of the
second valve, and opening of the third valve (the one between the ventricle and
departing artery). At this time, blood leaves the ventricle and enters the artery just

5
outside the heart.
Blood will not flow backwards, because these valves will force the blood to flow only in one
direction. After leaving the two-chambered heart, the blood travels to capillary beds in the
gills where it picks up oxygen and dumps its carbon dioxide. From there, the blood enters the
systemic circuit to delivering its oxygen to the tissue and to pick up waste carbon dioxide.
The blood then returns to the atrium and the process is repeated. Interestingly, respiratory
surfaces function best when the blood that is flowing through them is maintained at a low
pressure. Fish hearts does not generate high pressure when pumping blood to gills, and this
results in low blood pressure as blood enters the gills, and even lower pressure as it is leaving
the gills. This limits the rate at which oxygenated blood can be delivered to body, and
metabolism may be restricted as a result.

5
Double circulation occurs when oxygenated and deoxygenated blood are separated
into two distinct circuits that leave the heart. It is found in crocodiles, birds and
mammals and requires hearts that have either three or four chambers. Three-
chambered hearts evolved in the amphibians and in some reptiles. They consist of
two atria, and a single ventricle. This type of heart also has one-way valves to
prevent backflow of blood and is more evolutionarily advanced than the simpler
two-chambered heart. The beauty of this extra chamber is that it allows for two
separate circuits of blood flow.

In amphibians a pulmocutaneous circuit travels to the lungs and the skin where
gases are exchanged, while the systemic circuit travels to the rest of the body.
Deoxygenated blood from the body returns to the heart at the right atrium. At the
same time, the left atrium is collecting oxygenated blood from the lungs and the
skin. The blood from both atria is then pumped into the lone ventricle. The
ventricle then pumps the blood to both the circuits described previously. Like the
amphibians, reptiles have three-chambered hearts with two circulatory routes, but
blood is only oxygenated through the lungs. The circulation in the crocodilians has
some special adaptations that allow them to stay submerged for extended periods of
time.
Four-chambered hearts are also seen in all birds and mammals. These contain
two atria and two ventricles, and can be thought of as two separate (but connected)
pumps that work together, side by side each other. This heart contains a left atrium,
left ventricle, right atrium, and right ventricle (as diagrammed in this figure).

6
Movement of the blood in the four-chambered heart is maintained by the presence of four
one-way valves that prevent backflow. There are two atrioventricular (or AV) valves: one is
located between the left atrium & left ventricle, while the other is located between the right
atria and right ventricle. Each ventricle has a semilunar valve that exits the chamber, and
leads to an artery (arteries conduct blood away from the heart, while veins bring blood back
toward the heart). The four-chambered heart also allows for blood to be delivered in two
separate circuits. A major advantage of double circulation is that there can be two different
blood pressures in the pulmonary and systemic circuits. The right ventricle can pump blood
through the pulmonary circuit with low pressure, while at the same time, the left ventricle
generates much higher pressure into the systemic circuit to send the blood much longer
distances.

6
Why are some vertebrate hearts four-chambered, and others are not? Benoit
Bruneau and colleagues addressed this question using heart development gene Tbx5

In their experiment they compared Tbx5 expression in amphibians, reptiles, birds,

and mammals (illustrated in this figure). Their results showed that in amphibians
(with just a single ventricle) Tbx5 is expressed throughout the ventricle. In
reptiles (which contain an incomplete septum) Tbx5 expression is missing in part of
the right half of the ventricle. Finally, in birds and mammals (each containing two
ventricles) Tbx5 expression is missing in the right ventricle but is high in the left
ventricle. They concluded that a gradient of Tbx5 is required for the ventricle to
form two chambers and a complete double circulation. If Tbx5 was
experimentally induced in mice in a pattern like a lizard’s Tbx5 expression, the
mouse heart developed only three chambers (with no distinction between the left
and right ventricle).

7
In four chambered hearts, two sides of the heart are separated by a wall called the
septum. The right side of the heart carries deoxygenated blood from the right
ventricle, through the pulmonary semilunar valve, to the pulmonary circuit where
pulmonary arteries carry blood to the lungs. There, oxygen is picked up and carbon
dioxide is dumped. The freshly oxygenated blood returns by way of the pulmonary
veins to the heart at the left atrium. Blood is then moved through the left AV valve,
to the left ventricle. From there it is sent through the aortic semilunar valve, to
enter the systemic circuit, which begins at the aorta. This circuit delivers blood
everywhere else in the body (myocardium or heart muscle, head, neck, arms, torso,
trunk and legs). Oxygen is delivered to the cells of the body, and carbon dioxide
waste is picked up by the blood. The blood of the system circuit is sent to the vena
cava, which returns the blood to the heart at the right atrium. Finally, this
deoxygenated blood is sent through the right AV valve, and on to the right ventricle,
where the process is repeated.
Coronary arteries and veins give the myocardium (heart muscle) its own freshly
oxygenated blood supply. As blood exits the left ventricle through the aortic
semilunar valve into the aorta, it will enter the coronary circulation via the coronary
arteries, and then return back to the right atrium. The myocardium is exceptional at
removing oxygen from the blood: 75% of the blood here is deoxygenated, as
compared with about 40% that leaves the skeletal muscles and 25% leaving the
liver.

8
The cardiac cycle in organisms with four-chambered hearts can be observed in these
figures above and is also described in the flash presentation of the four-chambered
heart. During this process the atria contract at the same time (atrial systole), and
deliver blood to their respective ventricles below. The atria then relax (atrial
diastole), while the ventricles contract (ventricular systole), thus forcing the AV
valves closed. The blood of the ventricles is ejected from the heart through the now-
open semilunar valves. After completing its circuit, blood returns to the heart and
passively fills the atria during ventricular relaxation (ventricular diastole).
The AV valves only allow blood flow from the atria to the ventricle, when atrial
pressure is greater than that of the ventricles. So, when the pressure reverses itself,
the AV valves close and the myocardium shudders in response to the turbulent flow
of blood that is caused by this event. This creates the first part of the heart beat
(which we call a heart sound named “lub”). The second heart sound is caused after
the ventricles relax. Ventricular relaxation causes the pressure in the ventricles to
decrease, which results in the closing of the semilunar valves. This causes a similar
myocardial shuddering and the second heart sound (“dup”) that we hear.
The sequence of contraction in the heart is orchestrated carefully to ensure that the
atria contract first, forcing blood into the ventricles, followed by ventricular
contraction that sends blood out the top of the heart to the major distributing
arteries. This is controlled internally (with some external neurological influence). If
a vertebrate heart is disconnected from its body and is maintained in an isosmotic
solution, it will continue to beat. This is because it has a natural pacemaker built

9
within. In the four-chambered heart, this pacemaker is in the roof of the right atrium and is
called the SA (or sinoatrial) node. Here the cells spontaneously depolarize, which causes
them to contract. Recall that the myocardial cells are connected by gap junctions, so this
signal spreads throughout the right atrium, and into the left atrium. At this point, both atria
contract. There are no gap junctions connecting the cells of the atria and ventricles, so this
bioelectric signal must be carried to the ventricles another way. In the floor of the right
atrium, there is another cluster of cells called the AV (or atrioventricular) node. This area
will also spontaneously depolarize like the SA node, but at a slower rate. It is influenced by
the SA node, and will fire when receiving signals from myocardium of the right atrium. Thus
the faster rate generated by the SA node is the pacemaker of the cell. The AV node can serve
as a backup pacemaker in case the SA node fails. The AV node is neurologically connected to
the ventricles by way of the AV bundle, and will send a signal to the ventricles. The AV
bundle splits into two bundle branches as it passes down the muscular wall that separates the
ventricles. When these branches reach the apex (i.e. the lowest point) of the heart, they spread
out to the myocardium by way of specialized conducting (Purkinje) fibers, that act to
deliver the electrical signal to the myocardium of the ventricles. If this electrical sequence is
interrupted and the cells of the heart develop uncoordinated contractions, the condition of
fibrillation occurs. When this happens, a mechanical defibrillator may be used to shock the
heart and hyperpolarize all of its cells. This stops all of them from beating, allowing the
natural pacemakers to resume control of the cardiac rhythm.

9
Cardiac output is equal to the amount of blood that the heart pumps in liters per
minute. Cardiac output can be calculated as the heart rate (in beats per minute) X
stroke volume (cardiac volume ejected per beat), as shown in this figure and it
depends directly on the size of the heart and how often it beats.
A small animals’ high heart rates give them a greater cardiac output than would be
predicted based on size. This is because small animals have high metabolic
demands, which must be matched by cardiac output. This figure shows common
factors that affect both heart rate and stroke volume in humans.

10
This figure show an ECG wave and its corresponding electrical conduction events.
It outlines the P wave which is caused when the atria initially depolarize; this
directly leads to atrial systole. The P-Q interval is an interval in time, which occurs
as the electrical signal passes through the SA node, to the AV node, then into the
septum between the ventricles and to the apex of the heart. As the electrical wave
spreads across the ventricle, the huge QRS Complex is generated. This directly
leads to ventricular systole. A T wave occurs when the ventricles repolarize, back to
resting state.

11
A heart’s primary function is to move the fluid that contains nutrients, respiratory
gases and waste products. In mammals, this is blood (shown in this figure), and it
has two major components. The liquid portion is called plasma and the cell-related
components are sometimes referred to as formed elements. The plasma makes up
about 55% of the blood volume and is mostly water. Within the plasma there are
dissolved nutrients, hormones, biologically important ions (called “electrolytes”)
and proteins.
There are three basic formed elements: erythrocytes (red blood cells), leukocytes
(white blood cells) and platelets (thrombocytes). Plasma is the liquid portion of the
blood and is important in carrying the bloods cells throughout the body. Notice from
the figure above that plasma is over half of the blood by volume, and of that portion,
more than 90% of it is water. The other 9% of that portion consists of proteins and
dissolved solutes such as the electrolytes (sodium ions, chloride ions, potassium
ions, etc.).
The proteins in the blood create osmotic pressure. Remember that dissolved
particles will cause water to flow towards them by osmosis (we call this osmotic
pressure). This osmotic pressure helps to counteract the effects of blood pressure in
the capillary beds, which tends to squeeze fluid out of the bloodstream and into the
surrounding tissue spaces. Most of the fluid that leaves the capillary beds is returned
because of this higher osmotic pressure in the blood. The remaining fluid is returned
to the blood stream via the lymphatic system.
There are three major types of plasma proteins and they include albumins,
globulins, and fibrinogen. Albumins are the most abundant and create the highest amount of
osmotic pressure. Some globulins act as antibodies, and others are involved in transportation
of organic molecules. Fibrinogen is essential for blood clotting. If the clotting factors are
removed from plasma, we call it serum. Serum is found in the fluid between cells (interstitial
fluid), and is clinically important in replacing lost fluid in patients.

12
All formed elements are derived from the same type of cell, a multipotent stem
cell. A stem cell is one that can give rise to many different cell lines. Multipotent
stem cells grow and differentiate in red bone marrow, found in the shafts and ends
of long bones (especially in children), and in the flat bones of the body, such as the
hip bones and skull. They are also found in the vertebrae. The figure above shows
how one of these stem cells can divide and become many different types of cells. If
the stem cell produces an erythroblast, then an erythrocyte or red blood cell can
be formed. Erythrocytes function to carry oxygen and to manufacture some
important proteins. They are under a lot of physical stress, and last anywhere from
90-120 days, so they are constantly being replaced. If the stem cell produces another
type of cell, such as a lymphoblast, monoblast or myeloblast, then they will
differentiate into one of the leukocytes or white blood cell types. Finally, if the stem
cell forms a megakaryoblast, then this cell will break apart and form fragments,
known as platelets or thrombocytes. These aid in blood clotting.
Leukocytes or white blood cells (WBC’s) are important in the defense against
foreign invaders and they exist in five different forms, seen in this figure. Their
numbers are much lower than that of red blood cells, however their importance
cannot be understated, and they can be produced at an extraordinary rate. We
categorize leukocytes by whether or not they have granules. Those that do, are
called granulocytes and those that do not are called agranulocytes. The three type
of granulocytes are distinguished by how they react to certain histological stains -
such as those that stain with a basic stain (basophils), those that stain well with a
neutral stain (neutrophils – the most abundant leukocyte) and those that stain best
with eosin, an acidic stain (eosinophils).
The agranulocytes include the lymphocytes and the monocytes. Lymphocytes are
the second most abundant type of leukocyte and are responsible for immunity
specific to bacterial and viral infections.

14
Megakaryocytes are large cells that remain in the bone marrow and give rise to
platelets (also called thrombocytes). This figure shows how portions of the
megakaryocyte pinch off portions of themselves to form the platelets, which are
released in the blood stream where they survive for about 10 days. These cell
fragments play a very important role in blood clotting.

15
Red blood cells or erythrocytes (shown throughout the figure) have no nucleus and
very few organelles, but the cells that they come from are very active and have a
nucleus. As they mature, the organelles (including lots of Rough ER) and the
nucleus are destroyed or removed. During its development, the cell manufactures
and assembled lots of hemoglobin proteins which surrounded four iron molecules
(shown in the next slide). The hemoglobin molecule contains four protein subunits,
each with its own heme group that contains an iron center. Each hemoglobin
molecule can carry four oxygen molecules (one at each of the iron molecules).
Oxygen is easily bound and unbound here. But if carbon monoxide (CO) is picked
up by these heme groups, they are difficult to remove. Therefore, CO poisoning
interferes with the blood’s oxygen carrying ability by blocking available heme
binding sites on the hemoglobin molecules. Erythrocytes last about 3-4 months and
are being constantly replaced. Some of the iron of old erythrocytes is recycled by
activities of the spleen and liver, however this must be supplemented by dietary iron
because of the inefficiency of this process.

16
There are several different blood pigments in various animal groups. The first,
hemoglobin (illustrated in this figure) is found in most vertebrates and is carried in
the erythrocytes; it is capable of carrying lots of oxygen because of a central heme
group, associated with an iron molecule (bottom figure), and is surrounded by 4
protein subunits (and as previously described). Hemocyanin (another pigment) is
found in many invertebrates such as crustaceans and earthworms. It also delivers
oxygen, but floats free in the hemolymph, using copper to bind oxygen, giving the
hemolymph a blue-green color. A third pigment, hemerythrin (found in the marine
invertebrate sipunculids and brachiopods) also carries oxygen. Like hemoglobin,
hemerythrin is bound in blood cells, has iron associated with it, but it does not
contain heme.

17
When there is not enough oxygen in the blood, the kidneys are involved in a
negative feedback loop to correct the problem. First, the kidneys detect the stimulus
of low blood oxygen levels. Next, they produce and secrete a hormone called
erythropoietin (EPO) into the blood stream. This hormone targets the bone
marrow and promotes production of more red blood cells. This ultimately leads to
a higher blood oxygen concentration (which is the opposite of the initial stimulus –
i.e., low blood oxygen concentration, and this is a self-regulating system).
This picture shows Lance Armstrong, a famous American cyclist whose multiple
first place medals for winning the Tour de France were vacated. After many years
and numerous allegations of cheating, it was confirmed that he used EPO to “blood
dope” and gain a competitive advantage.

18
Primates are a group of mammals to have ABO blood types. This figure shows how
human red blood cells can have either type A (Group A) or B (Group B) surface
glycoproteins or both (Group AB), or neither (Group O). These proteins act as
antigens and can elicit an immune response in someone who does not have these
proteins, and whose immune system sees them as ‘foreign’ antigens. Type O blood
lacks both A & B antigens and will not create an immune response into a person of
A, B, or AB blood types. Someone with type AB blood can receive blood from
blood types A, B or AB because their body recognizes either A or B glycoproteins as
self, and we call type AB the universal acceptor.
This figure does not show the Rh antigen, which is also antigenic in someone who
does not have this glycoprotein. If Rh is absent, we say that the person is Rh
negative. Thus, a person with type O – (read as “O negative”) blood lacks A, B, and
Rh: thus, we call type O - blood the universal donor and will not elicit an immune
response when infused into anyone. If Rh is present, we say that they are Rh
positive. A person with A, B, and Rh is AB+ (AB positive), and can safely receive
any combination of these antigens without danger of an immune response.

19
When a blood vessel is damaged, platelets arriving in the blood will stick to the area
and form a clot. Some very complex enzymatic reactions are necessary and certain
proteins must be present. If some of these proteins are missing, then a clotting
disorder may occur, such as the inherited disorder hemophilia.
First, damaged cells with their exposed collagen activates platelets, causing them
to congregate and stick to the area of a wounded blood vessel.
Second, the damaged cells and platelets release chemicals that lead to the
conversion of the inactive protein prothrombin to thrombin.
Third, thrombin causes the formation of fibrin (from the inactive protein
fibrinogen), which forms a meshwork that traps platelets, erythrocytes and
leukocytes. This forms a network to which erythrocytes and platelets stick.
Ultimately, these events form a tangled, sticky mass, and leads to sealing of the
wound.

20
Blood vessels are named according to their position in the path of blood flow.
Arteries are defined as vessels that carry blood away from the heart, whereas
veins are blood vessels that carry blood back toward the heart. An artery has three
layers within its wall, including one that is loaded with smooth muscle. The
innermost layer, which surrounds the lumen is called the endothelium, and it is
associated with a layer of smooth muscle. A layer of connective tissue surrounds
the blood vessel. The smooth muscle and other layers will maintain pressure on the
blood, which helps to maintain overall blood pressure. As arteries get further away
from the heart they split into smaller vessels called arterioles, which are barely
visible to the naked eye. These vessels are composed mostly of smooth muscle, and
they are very important in the control of blood pressure. The normal internal
diameter of the artery is smaller than that of the adjacent vein (figure c). This is
because veins do not have thick muscular walls, and will expand easily. Therefore,
pressure in the veins is much lower than in adjacent arteries.
Arterioles have the ability to dilate or constrict in order to control blood distribution
to tissues. Arterioles end by branching into capillaries. These microscopic networks
of blood vessels is where exchange of gases, nutrients and waste products occurs
between the blood and the surrounding tissues or tissue spaces. Blood leaves
capillaries and enters venules, then finally veins. At the entrance to many capillary
beds are specialized sphincter muscles called precapillary sphincters, which act to
regulate the blood flow to these areas.

21
Capillaries are microscopic blood vessels that are specialized to act as the site of
gas and nutrient/waste exchange. They have a single-celled layer of endothelium
on a basement membrane and are the smallest and narrowest vessels in the body.
Red blood cells pass through microscopic capillaries in single file (left figure).
Oxygen and nutrients will leave the systemic capillaries to supply the surrounding
tissue, while carbon dioxide and waste products will enter the capillaries, to be
carried away from the area (right figures).
The situation is complicated because the blood pressure is higher at the arterial
end, as compared with the venous end of the capillary bed. The blood has a lot of
proteins, which creates osmotic pressure within the blood plasma, and draws fluid
into the capillaries. Remember that osmosis occurs toward the direction of the
dissolved particles, which in this case, are the plasma proteins. The blood pressure
in the arterial area is greater than the opposing force of osmosis, thus forcing fluid
out of the capillaries in this region. In the venous end, however, the blood pressure
drops, and the plasma osmotic pressure remains the same. Now, the osmotic
pressure (drawing fluid into the capillaries) is greater than the fluid pressure forcing
water out of the capillary, so that water enters the capillary. Thus, in the arterial end
water leaves the capillary, and in the venous end, water is recovered. Overall, more
fluid is squeezed out of the capillary and into the extracellular fluid. Therefore,
some fluid is not recaptured by the capillaries and must be recovered through
another mechanism. Normally, the lymphatic system will collect fluid that is not
captured and return it to the blood.

22
In humans, the lymphatic system includes several organs and an extensive network
of lymphatic vessels. Functions of the lymphatic system include:
• Return of excess extracellular fluid to the bloodstream,
• Transportation of fats from the small intestine to the bloodstream,
• Removal of aged blood cells and debris from the bloodstream,
• Defense against bacteria and viruses.
This figure shows many of the major features of the human lymphatic system.
Notice the abundance of lymph nodes and how they are concentrated in the armpits
and neck. They are also abundant in the inguinal region, near the groin (not shown
here).

23
As blood travels through the capillary beds of the systemic circuit and into the
venules and veins, the system has lost a lot of fluid pressure. The walls of veins are
under low pressure, and the blood needs assistance in moving through the area back
towards the heart. One way valves are present in veins (shown above), which keeps
the blood flowing in the proper direction and prevents back flow. Veins are often
surrounded by skeletal muscle, which during exercise will act to compress the vein,
thus moving blood along in veins. There are also other anatomical strategies that
exist to compensate for the low blood pressure of veins. Often they are located are
near arteries, or are strategically located in the thoracic cavity near the expanding
lungs. These can exert pressure on the veins, and will squeeze the blood
downstream.

24
Blood pressure is the force exerted by blood on the walls of blood vessels. This
force is originally produced by the heart, the smooth muscle surrounding the vessels
and the anatomic features of veins just described (one way valves and skeletal
muscle pump). During the cardiac cycle, we distinguish a cardiac contraction
(called systole) from a cardiac relaxation (called diastole). The “e” at the end of
these two terms is pronounced as a hard “e”. The pressure generated by the heart
was traditionally measured by how high that pressure is able move a column of
liquid mercury. The figure above shows a gauge, instead of a column of mercury,
although many are still used today. The “mm” stands for millimeters and there are
25.4 mm in 1 inch. We call this blood pressure, and it is important because it
moves blood within the blood vessels. However, if blood pressure is too high, then it
can wear out the blood vessels over time, and also lead to organ damage.
Most people have had their blood pressure measured, so it is helpful to understand
what the numbers mean. Perhaps your blood pressure was taken, and written down
as 117 / 72. The first (and highest) number recorded is the pressure that is produced
during a cardiac contraction (remember that this is called “systole”) and we refer to
it as systolic blood pressure. The last number recorded is the diastolic blood
pressure, taken during diastole, or cardiac relaxation. Healthy blood pressure is
usually considered anything below 120 / 80. When a blood pressure cuff is inflated
it will push on the soft tissue, which then compresses the artery. In the upper arm
the artery of concern is the brachial artery (which feeds the two arteries of the
lower arm = radial and ulnar). So, when the brachial artery is compressed by

25
pressure greater than systolic blood pressure, the artery is completely closed. A clinician
measuring blood pressure will slowly release air pressure in cuff – this can heard as that
hissing sound. At the same time they are listening (or auscultating) for any sounds, caused by
blood getting through a partially blocked artery. This will occur only when the cuff pressure
becomes equal to, or less than systolic blood pressure. The systolic blood pressure is recorded
when they hear the first sound. As cuff pressure decreases further, the quality of the sounds
will change as the artery opens up, until the artery is completely open. The last sound that
they hear is when they record the diastolic blood pressure.

25
Blood vessels may become blocked by plaque formation. The figure above shows
how solid masses, called plaques, can line the lumen of blood vessels, causing
atherosclerosis. This is particularly dangerous when this occurs in the coronary
arteries, blocking off the blood supply of the myocardium (i.e., heart muscle). Some
causes of plaque formation include sustained hypertension (elevated blood
pressure). Another danger of atherosclerotic plaques is the potential for a clot to
adhere to the area. If the clot remains stationary it is called a thrombus, but if it
comes loose and travels in the blood stream it is considered a thromboembolism or
simply an embolism. An embolism may lodge itself in the arteries of the heart or
the brain, causing often fatal complications, if untreated.
A stroke or cerebrovascular accident (CVA) may happen if a cranial arteriole bursts
or becomes blocked. Symptoms may include numbness, blindness in one eye, one
side paralysis or difficulty speaking.
An MI (myocardial infarction) or heart attack can occur if any portion of the heart
lacks sufficient blood supply. Symptoms may include chest pain (angina pectoris)
and left arm pain that may radiate upward to the jaw.
Strokes and heart attacks are often permanently debilitating or even fatal. Any sign
of either should not be ignored and emergency medical care should be
immediately sought. Patients that come into emergency departments with signs of
either are fast tracked and seen promptly by ER physicians. Time is essential
because permanent damage is often preventable with proper intervention.

26
One way to treat a clogged coronary artery is through the use of coronary bypass
surgery (seen above right). During this procedure, a vein is taken from one part of
the patient (often the great saphenous vein of the leg) and is used to go around the
blocked portion of the coronary artery. Often multiple coronary arteries are blocked
so the procedure may be a double, triple, or quadruple bypass surgery, indicating
that two, three or four arteries were bypassed.
Another, less invasive procedure is angioplasty, seen in the figure on the left, where
a plastic tube with a mini-balloon attached is inserted in an artery of the arm or leg.
It is snaked to the coronary arteries and the balloon is inflated to relieve the
blockage. Modifications of this procedure may include a small drill-like device
where the plaques are scraped away.
Now, let’s take a look at how gases are handled by respiratory systems of animals.

27
Air is composed of about, 21% oxygen, 78% nitrogen, and roughly 1% carbon
dioxide and other gases. In an examination of respiratory gases, nitrogen is usually
ignored because it is generally not part of the respiratory process, unless pressurized
air is breathed. Exchange of O2 and CO2 depends on the solubility of the gas in
water and the rate of diffusion of that gas.

Atmospheric pressure is the amount of force that is exerted by the weight of the
atmosphere on the body surfaces of animals. It is measured in mmHg (mm of
mercury), and at sea level it is equal to 760 mmHg (also called 1 atmosphere).
Atmospheric pressure decreases at higher elevations, and it is the sum of the
individual (or partial) pressures of each gas in proportion to their amounts,
illustrated in this figure (this is called Dalton’s Law of Partial Pressures). The
percentage of gases within the atmosphere remain the same, regardless of altitude,
but lower atmospheric pressure results in lower partial pressures. So, at sea level the
partial pressure of oxygen is 160 mmHg, but at increased elevation, the amount of
oxygen in the air is still 21%, but the partial pressure drops to 112 mmHg at 10,000
feet, and at 18,000 feet it is about half that of sea level. Diffusion of gases into and
out of the blood is driven by partial pressure gradients, so the rate of oxygen
diffusion into the blood is lower at higher elevations.
Gases dissolve in solutions, such as fresh water, sea water or body fluids. Most
gases dissolve poorly in water, and several factors influence solubility. Higher
pressures will result in forcing more gas into solution, up to a limit for each gas.
Cold water dissolves gas better than warm water, and the presents of other solutes

28
decreases the amount of gas that dissolves into solution. Hence, saltwater and blood both
dissolve less O2 than pure water. This has implications for the way that gases are carried in
animal circulatory systems.

28
Respiration occurs when gas is exchanged in an organism. This can occur when we
breathe, between the lungs and the bloodstream (external respiration), or between
the blood and the tissues (internal respiration). The oxygen that organisms take in
can then be used in the production of ATP during the process of cellular respiration.
There are some remarkable adaptations that organisms have developed for gas
exchange, all of which ultimately rely on diffusion. Cell respiration depletes
oxygen levels, and increases carbon dioxide levels. It is essential for an animal’s
survival, that the oxygen is replenished and carbon dioxide is removed.

29
In order to facilitate diffusion, all animal respiratory systems must meet three
requirements:
1. Respiratory surfaces must stay moist because living cell membranes are moist.
Therefore gases diffusing into or out of the body must be dissolved in water.
2. Respiratory surfaces must be thin enough to promote diffusion.
3. Respiratory surfaces must have enough surface area to allow adequate gas
exchange.
The types of respiratory systems found in animals include those that exchange gases
through: body surfaces, gills, tracheae, & lungs.
Some other features of gas-exchange organs include a high surface area for gas
exchange with extensive blood flow over thin, delicate structures.
Organisms in moist environments often lack specialized respiratory structures and
move gases directly through body surfaces. For instance, the unicellular alga
Ventricaria ventricosa, which may be up to 5 cm (2 inches) in diameter exchanges
gases directly across its cell membranes. Some animals, like the flatworms, have
flattened bodies which keep all cells close to the surface. Another strategy is to
have cells far from the surface to require little oxygen, such as the jellyfish. A third
strategy is to bring the watery environment close to the cells, which is what we
see in the sponges.
Amphibians and earthworms use their skin as a respiratory organ, and can do so

30
because there are capillaries very close to the skin. Amphibians are the only vertebrates to
rely on their skin for gas exchange under water. It is extremely important to keep this surface
moist in order to facilitate gas exchange, and in this photo (© Ken Thomas) it is obvious that
the frog’s skin is wet. Amphibians are nearly unique in the animal world because they utilize
both lungs and gills. The lungfish is believed to be very much like the ancient ancestors to the
amphibians. In a developing tadpole, gills are present which allow the animal to be totally
aquatic. During metamorphosis, lungs develop as legs grow and the tail deteriorates. This
specialization allows the frog to become somewhat terrestrial, however it must remain moist.
This is because the skin also acts as a respiratory organ.

30
Gills, another type of organ for gas exchange, are found in many aquatic animals.
These structures have elaborate branching or folding patterns specifically designed
to increase surface area, which in turn increases diffusion. Some species such as the
nudibranchs (sea slugs) illustrated here have external gill. However many aquatic
organisms such as the fish shown have internal gills.
External gills vary widely in appearance but all have a large surface area with
extensive projections. They may exist in one body area or be scattered over a large
area. They are unprotected and subject to damage, and energy is required to wave
gills back and forth. Their obvious appearance and motion may attract predators.

31
Gills are remarkable structures. They have delicate membranes that lay over dense
capillaries. In fish, an operculum covers the gills, giving them internal gills. As a
fish breathes, it takes water into its mouth, passes it over the gills and ejects it out
the opercula. Fast swimming fish like tuna and mackerel swim with their mouths
open and create a current in this way. The slow swimmers and sedentary fish will
use their opercula to pump water over the gills. Water has only a very small
percentage of dissolved oxygen, as compared with the atmosphere, so aquatic
breathing animals have a serious challenge in their attempt to extract oxygen from
the water. Moving sufficient amounts of water over the gills also requires
tremendous energy, thus fishes have developed a very effective adaptation to
maximize gas exchange. If blood and water flowed in the same direction, as gaseous
transport occurred, the concentration gradient would deteriorate. At this point, gas
exchange would decrease. The figure above shows how water in the fish gill flows
across the capillary bed; this in the opposite direction (i.e. “countercurrent”) of the
blood flow within the capillary bed. In this way, the exchange of oxygen and carbon
dioxide is maximized.

32
In the fish gill, the blood is moved in the opposite direction that water flows. When
there are two currents that flow in opposite directions like this, we call it a
countercurrent system. Because gases are being exchanged here, it is a
countercurrent exchanger. The figure above shows how two substances separated
by membranes will have maximal exchange when they flow in opposite directions,
as compared to when their flow is concurrent (same direction). There are many
examples of countercurrent exchangers in the animal world. The reason that a
penguins foot does not melt ice is that the blood is cooled as it travels down the leg,
and is then warmed back up as it returns to the body, via countercurrent heat
exchange.

33
Insects respire using a simplistic, but effective tracheal system, which is
completely independent of the circulatory system and is made up of the
polysaccharide chitin. This network of tubules (the trachea) are connected to the
outside via tiny openings called spiracles, and carry oxygen to the entire body.
Tracheae branch into tracheoles, that terminate near every body cell, and oxygen
diffuses directly into the body cells. Often you can observe an insect ventilating the
tracheal system through rhythmic body movements. The trachea penetrate many of
the body tissues with microscopic channels, and carry gases to and from the cells.
This mechanism is very efficient and supports insect flight muscles, with the
highest metabolic rate currently known.

34
Most of us learned at an early age that lungs are paired structures that we use to
breath. Lungs receive deoxygenated blood from the heart, then return that same
blood back to the heart after it has been oxygenated. Lungs are used by all air-
breathing terrestrial vertebrates, except the lungless salamanders. Lungs use
negative pressure filling. Essentially, what a lung does is to create a small vacuum
in order to draw in air. Vacuums are caused by pressure differentials in the air.

From a physical standpoint, we know (according to Boyle’s Law) that in gases,

pressure and volume are inversely related to each other. This is illustrated in this
figure. What this means is that as one goes up, the other goes down. So if pressure
in a lung increases, its volume will decrease (and vice versa). Because of this,
expanding and compressing the lungs creates pressure gradients (differences) that
animals use to move the air.

35
In reptiles, the lungs are fully developed. In aquatic species such as turtles and sea
snakes, the animal must surface regularly to breathe, however the skin may be
minimally used for a little gas exchange in some species. The lungs of reptiles are
more fully developed than the amphibians, in order to compensate for a lack of
respiration through the waterproof skin. Alligators have a very specialized system
called a ‘hepatic piston’ where the liver is pulled back in a complex series of
muscular movements involving the diaphragm, to make room for expanding lungs.
Their respiratory system is often compared with that of the birds.
Birds have the most amazing respiratory system of all terrestrial animals. It is highly
efficient because of its multiple chambers. Air in the lungs never has to pass back
the way that it came, and significant amounts of oxygen can be extracted in this
way. This is accomplished by surrounding the lungs with a posterior air sac and
anterior air sac. When the bird breathes in as shown in this figure on the left,
inhaled air is brought first through the trachea. Next, this fresh air is delivered to
the posterior air sac and to the lung. This forces used air into the anterior air sac.
Upon breathing out, as demonstrated in the right hand figure, the chest is deflated
and as a result, both posterior and anterior air sacs are compressed. The used up air
in the anterior air sac is forced out the trachea AND fresh air from the posterior air
sac is delivered to the lung. Within the lung, parabronchi exist, which are a super-
efficient deliverers of gases between the lung and the bloodstream.
Notice that air goes into and out of the lung in different places. This makes gas
exchange more efficient as compared to the mammalian lung which only has a

36
single open, through which air enters and exits.

36
Mammals, like the lunged-amphibians, reptiles and birds, have also developed
specialized respiratory systems that interact closely with the circulatory system to
promote transfer of gases between the environment and the body cells. In contrast to
the avian respiratory system, the mammalian respiratory system passes both fresh
and used air back and forth across the same respiratory surface. We tend to think
about mammalian respiratory systems as being divided into two generalized
regions: these are the conducting region where gases are delivered to and from the
lungs, and the gas-exchange region, where gases are transferred between the
atmosphere and blood near the lung. The left figure shows an overview of the
human respiratory system. Air entering travels through the conducting region and
into the gas exchange region as follows: nose or mouth, pharynx, trachea,
bronchi, bronchioles, alveoli. Air is warmed and humidified in the nose and mouth,
and mucus and hairs in the nose help to remove dust from the air.
Gas exchange takes place in the respiratory membrane of the alveoli (right
figures). It is made up of the alveolar tissue, a single layer of epithelial cells, that is
surrounded by a network of capillaries. The alveoli are a series of tiny air sacs that
occupy a surface area of nearly 1500 square feet (that’s more than half of a tennis
court). Gas exchange occurs in the alveoli through diffusion. Air within an alveolus
of the lungs is richer in oxygen and lower in carbon dioxide as compared with the
gases carried in the nearby capillaries. The respiratory membrane is only two cells
thick, which allows for rapid diffusion of gases. The alveolar membrane is always
moist, and a substance called surfactant is secreted by specialized cells. Surfactant

37
lowers surface tension and helps the thin wet membrane from sticking together upon
exhalation. If surfactant were absent, the alveoli would constantly collapse when a person
exhaled.

37
Which do you think comes first, chest expansion or lung inflation? In other words,
does your chest expand because your lungs inflate, or is it the other way around?
The answer to this question can be discovered when one examines the mechanics of
breathing. The figure above shows how inspiration (inhalation) and expiration
(exhalation) occurs. Here, the mechanics of inspiration are shown. Essentially, the
ribcage expands upward and outward, while the diaphragm moves downward. These
events cause the thoracic cavity to expand. There are two membranes that surround
the lung, which we call the outer and inner pleural membranes. The outer pleural
membrane is stuck to thoracic cavity wall and to the inner pleural membrane, which
itself is stuck to the lung. So, when the thoracic cavity expands, it pulls on the lung
and increases its volume, while creating suction. This causes the pressure within the
lung to decrease, and is a vacuum, so that air will flow into this low pressure area
from the outside.
Now try to answer the question posed above – does the chest expand because the
lungs have inflated, or do the lungs inflate because the chest first expands?
Normally, the chest expands first, which then causes the lungs to inflate. When a
person is on a respirator the opposite occurs because the lungs are mechanically
inflated via a machine first, and the chest expands as a result. Normal expiration is a
passive process, where the muscles between the ribs and diaphragm relax, causing
the thoracic cavity to return to its smaller relaxed size. This, along with the elastic
recoil of the lung tissue, puts increased pressure on the air in the lungs, which then
flows out of the body.

38
One of the keys to the lung volume increase during chest expansion is the presences of the
pleural membranes. This figure shows that a serous membrane surrounds and is directly in
contact with the lung – this is the visceral pleura (visceral tells us that it lies in direct contact
with an organ while pleura tells us that it is associated with the lung). Another membrane, the
parietal pleura, is the serous membrane that lines the cavity that houses the lungs (the
pleural cavity). Both membranes contact each other and there is a potential space between
them, with no air, and the two membranes are stuck together.
As the chest expands and the parietal pleura pulls away from the lung, the negative pressure
of the pleural space and cohesion between the two membranes, pulls on the visceral pleura
and lung to make it expand. This creates the slight pressure vacuum of negative pressure
filling which acts to draw air into the lung from the bronchi.

38
This figure shows the pleural membranes that are essential in creating the vacuum
within the lungs, which initiate negative pressure filling. If an event occurs where
atmospheric air enters the pleural space (such as during an open chest wound), the
parietal and visceral pleura do not remain in contact. The resulting loss of contact
between the membranes may lead to a collapsed lung.

39
Mammals breath in a process known as tidal ventilation. In humans, during a
normal tidal volume the volume of air breathed in and out at rest is about 500 ml
(TV or VT in this figure). The lungs can be deflated or inflated further, which is
represented by the expiratory & inspiratory reserve volumes (ERV / IRV).
However, the lungs never completely deflate, and will contain a residual volume
(RV). This is because the lungs are held open by its adherence to chest wall (by way
of the pleural membranes). The only time that a living mammals lungs are empty is
prior to their first breath.
Because the respiratory membrane in our lungs is wet, surface tension is an force
of attraction between water molecules at the air/ liquid interface across the alveoli
that must be contended with. Unchecked, this interaction would cause a collapse of
the alveoli, and every breath would be as difficult as the very first one we took.
During the late stages of fetal development, type II cells within the lungs begin
secreting the substance surfactant. This is a mixture of proteins and lipids with
polar and nonpolar properties, and it facilitates lung inflation by reducing surface
tension. This prevents respiratory membranes of the lungs from sticking together
during an exhalation.

40
Now, we will shift our attention back to the blood, and how it handles oxygen that is
delivered via the respiratory system. Not enough oxygen is able to dissolve directly
into blood to support an animal’s metabolic needs. The way that these needs are met
is through the use of respiratory pigments which increase the amount of gas that
can be carried in a solution. So, in the blood, respiratory pigments may be contained
within red blood cells or in directly in the plasma. Typically these pigments contain
proteins with one or more metal ions.
Within red blood cells, there is an abundance of the molecule hemoglobin. The
figure above shows the structure of a single hemoglobin molecule which contains 4
protein subunits and a single iron-containing heme unit. A single hemoglobin
molecule binds up to 4 oxygen molecules. Each red blood cell has about 280 million
hemoglobin molecules, and can transport more than one billion oxygen molecules.
At the lungs, oxygen enters the bloodstream and is bound by the protein hemoglobin
that is contained within the red blood cells. The blood is then carried to the body
tissues where oxygen is delivered. When the blood arrives at the tissue spaces,
oxygen is released from the red blood cells and it diffuses into the plasma, then
across an endothelium that lines the vessel, and into the cells of the body tissue.
The blood of some organisms such as crabs contains hemocyanin, a copper based
pigment that also helps carry oxygen. All of the respiratory pigments have a high
affinity for oxygen, and its binding is noncovalent and reversible.

41
The transport of carbon dioxide is much more complex than that of oxygen in the
bloodstream. This allows the brain to closely monitor carbon dioxide concentrations
via the presence of some products that are released in the reactions described below.
The figure on the left shows how carbon dioxide is transported from the cells of the
body tissue, into the blood stream. About 10% of the carbon dioxide is carried
dissolved in the plasma, about 20% is bound to hemoglobin, and the remaining 70%
is carried as bicarbonate ion (HCO3- ). As carbon dioxide diffuses into the red blood
cells, in the presences of the enzyme carbonic anhydrase, it is coupled with water
and converted into carbonic acid in the following series of reactions:
H2O (water) + CO2 (carbon dioxide) → H2CO3 (carbonic acid) → HCO3-
(bicarbonate ion) + H+ (proton)
The bicarbonate ion diffuses out of the red blood cell in a swap with a chloride ion
(Cl-) and is carried dissolved in the plasma, while the proton is held by the
hemoglobin. When the blood arrives at the lungs (right figure), the bicarbonate ion
moves back into the red blood cells and is again swapped with a chloride ion. The
bicarbonate ion is combined with a proton to re-form carbonic acid. The enzyme
carbonic anhydrase catalyzes the split of this molecule to form water and carbon
dioxide. The carbon dioxide leaves the red blood cell and diffuses out of the plasma
and into the lung where it can be exhaled. If there is excess carbon dioxide in the
blood stream, this leads to an increased production in protons, which then drops
plasma pH. If this is not obvious to you, then please review pH in an earlier chapter
on chemistry in your textbook.

42
The oxygen-hemoglobin dissociation curve, shown above, indicates how
hemoglobin (Hb) has a variable affinity for oxygen depending upon several factors.
As the amount (or partial pressure) of ambient oxygen (shown as PO2 ) increases,
more oxygen is bound to hemoglobin to form oxy-hemoglobin (HbO2). When
ambient oxygen is low, less O2 binds to hemoglobin to remain as deoxyhemoglobin
(Hb). Notice the classic sigmoid-shaped (S-shaped) curve, which indicates that the
binding affinity of oxygen to hemoglobin changes as oxygen loads and unloads.
During low partial pressures of oxygen, oxygen binds quickly to hemoglobin
(indicated by the steepness of the curve). At PO2 of 10 mmHg about 10% of the
hemoglobin is bound to oxygen to form oxy-hemoglobin, at PO2 of 20 mmHg this
increases to 35% oxy-hemoglobin, and at PO2 of 30 mmHg there is over 50% oxy-
hemoglobin. As PO2 approaches 65 mmHg about 90% of the hemoglobin in the
blood is bound to oxygen, and the curve flattens out.

43
If the temperature increases, or if the pH decreases (which would be an indirect
result of increased carbon dioxide, and subsequent release of H+), the affinity for
hemoglobin decreases. The result of this is that at the tissue spaces where
metabolism is high (i.e., more heat and carbon dioxide are being produced), more
oxygen is unloaded. This physiological phenomenon, where the oxygen binding
affinity of hemoglobin is inversely related to acidity and carbon dioxide
concentration, first described by Danish physiologist Christian Bohr, is called the
Bohr Effect and is illustrated in the shift of the oxy-hemoglobin dissociation curve.
This curve will shift in response to the production of metabolic waste products.
Increasing amounts of CO2, H+ and high temperature make oxygen load and unload
easier, indicated by the shift in the curve to the right (where more oxygen is
unloaded at the same partial pressure).

44
In different species, the curve is similarly shaped, however those that have higher
metabolic rates will have a right-shifted curve, as shown in this figure. Smaller
animals need to unload hemoglobin more readily at any given temperature because
their higher metabolic rate dictates that they need more available oxygen.

45
Ventilation in many vertebrates is controlled by respiratory centers located in
brainstem. When it is time to breath, signals travel from the brain through nerves to
intercostal muscles and diaphragm, as illustrated in these drawings. When the lungs
are full, stretch receptors send signals to brain that lungs are inflated and this
inhibits the stimulus to contract, until the lung volume decreases upon exhalation.
The signals can be consciously overridden to increase or decrease the rate of
breathing, up to a certain point.
Chemoreceptors throughout the body monitor blood gases and pH. They are located
in the aorta, carotid arteries and the brainstem. Specifically, the act to monitor the
concentration of Hydrogen ions (pH), PO2 and PCO2 . The respiratory centers in the
brainstem will send the signal to increase breathing rate if the pH drops due to
increased acid production from anaerobic metabolism or increased carbon dioxide
from aerobic metabolism. In extreme cases of falling oxygen levels, the respiratory
centers will also respond in the same manner, but normally blood pH and CO2 levels
drive breathing rate.

46
Cardiovascular disease are conditions that affect the heart and blood vessels and
account for more deaths each year in the US than any other cause. Respiratory
diseases affect as many as 10% of the U.S. population and result in an estimated
300,000 – 400,000 deaths per year. Systemic hypertension (high blood pressure)
causes damage leading to the formation of plaque inside artery walls, blocking the
lumen and rarely has any noticeable symptoms. Thus hypertension is often referred
to as a “silent killer”.
Uncontrolled hypertension is dangerous for several reasons, including they it often
leads to plaque formation with arterial walls. Plaques are formed from the
accumulation of fibrous tissues, lipids and even smooth muscle cells. These may
lead to atherosclerosis where the arteries become hardened and narrow, like that
shown in this micrograph. Plaque deposits cause an artery to narrow and harden,
and large plaques may occlude (block) the lumen of an artery entirely. Coronary
artery disease results from plaque forming in the coronary arteries that supply the
heart muscle. Another danger of atherosclerotic plaques is the potential for a clot to
adhere to the area. If the clot remains stationary it is called a thrombus, but if it
comes loose and travels in the blood stream it is considered a thromboembolism or
simply an embolism. An embolism may lodge itself in the arteries of the heart or
the brain, causing often fatal complications, if untreated.

47
A stroke or cerebrovascular accident (CVA) may happen if a cranial arteriole bursts
or becomes blocked. Symptoms may include numbness, blindness in one eye, one
side paralysis or difficulty speaking. An MI (myocardial infarction) or heart attack
can occur if any portion of the heart lacks sufficient blood supply. Symptoms may
include chest pain (angina pectoris) and left arm pain that may radiate upward to
the jaw. Strokes and heart attacks are often permanently debilitating or even fatal.
Any sign of either should not be ignored and emergency medical care should be
immediately sought. Patients that come into emergency departments with signs of
either are quickly seen. Remember that time is essential because permanent
damage is often preventable with proper intervention. During an MI localized
regions of heart muscle will die when the blood supply is cut off and dead cardiac
muscle does not regenerate.
Cardiac angiography can detect narrowing of coronary vessels and balloon
angioplasty, shown here, can be used to widen the lumen of narrowed vessels. In
this procedure a plastic tube with a mini-balloon attached is inserted in an artery of
the arm or leg. It is snaked to the coronary arteries and the balloon is inflated to
relieve the blockage. Modifications of this procedure may include a small drill-like
device where the plaques are scraped away.
Coronary artery bypass uses a healthy blood vessel to replace a blocked coronary
artery. During this procedure, a vein is taken from one part of the patient (often the
great saphenous vein of the leg) and is used to go around the blocked portion of the
coronary artery. Often multiple coronary arteries are blocked so the procedure may

48
be a double, triple, or quadruple bypass surgery, indicating that two, three or four arteries
were bypassed.
When a heart completely fails, alternatives include replacement with artificial hearts or with a
donated human heart. Heart transplants are often the best option, however the patient must
take immunosuppressant drugs for the rest of their life due to risk of tissue rejection.
Unfortunately there are not enough donors to meet the demands for donated hearts. Artificial
hearts often end up being a source of some dramatic infections and are not a preferable
option. Studies are underway to see if human heart valves and human heart tissue can be
grown and inserted safely into patients.
Fortunately, many of these problems are preventable. The best solution for cardiac issues is
to prevent them whenever possible. This means that the patient must take responsibility for
their well being early on in life and continue to live a heart healthy lifestyle throughout their
adult years.

48
There are many types of lung disorders, both temporary (acute) and permanent
(chronic).
Pneumonia, is one of the acute ones, where the alveoli fill with fluid – this
interferes with proper gas exchange. Bronchitis, is also temporary where the
bronchi become inflamed and filled with mucus, interfering with gas exchange.
Asthma may a chronic illness with some acute symptoms; here, the bronchi and
bronchioles become susceptible to irritants, which causes the smooth muscle to
spasm and reduce the diameter of the airway.
Some chronic illnesses include pulmonary fibrosis, where the normally elastic lung
tissue is replaced with fibrous tissue – this makes inflation of the lungs very
difficulty. Pulmonary tuberculosis is a bacterial disease which features
encapsulation of the bacteria within the lungs. This is a difficult disease to manage
because of the evolution of incredibly drug resistant strains of Mycobacterium
tuberculosis. This is a curable disease but might leave the lung tissue damaged.
Emphysema (shown in this figure) occurs when the alveoli become distended and
damaged. This reduces lung capacity and elasticity, and causes all phases of
breathing to become difficult. The extent of lung damage may be severe, and this
disease reduces the elastic quality of lungs and total surface area of alveoli. As a
result there is reduced blood oxygen that accompanies poor lung function. Although
there are several causes, over 85% of known cases are directly due to smoking.

49
Smoking is a tough addiction to crack, as some of us have experienced firsthand. It
is known that cigarette companies have historically spent excessive resources
determining how to get people to start smoking, and how to keep them smoking. For
example, the tobacco industry has targeted specific populations and attempted to
promote smoking as chic and stylish for women, as reported by the Harvard School
of Public Health. Cigarette smoking is known to cause all sorts of long term health
problems, beginning with lung functioning, but also include cardiovascular issues
such as heart attack and stroke. We’ve all seen the pictures, like those above of the
healthy and diseased lungs.
Lung cancer is a very dangerous form of cancer and is often (but not always) caused
by cigarette smoking. This is a progressive disease and if it is caught before the
cancer metastasizes (becomes capable of causing other cells to become cancerous)
the tissue can be removed. If you smoke, acknowledge that it is you are risking your
health. This is a brutal illness! I’ve seen some otherwise healthy non-smokers
people die from this disease in the prime of their lives, leaving young children
behind. If you smoke, you are putting yourself at great risk for lung cancer (and
other diseases). If you get lung cancer, you will suffer tremendously and so won’t
the people you love. If you are addicted to nicotine, it is a difficult habit to break but
there are many resources. Even if you have smoked for many years, stopping
smoking will decrease your risks for this and other diseases such as stroke and heart
attack.
I know that it is hard to quit smoking cigarettes, as I busted that addiction myself. It
can be done, if the smoker is motivated and stays determined. Good sources of

50
motivation include better health, not having to stand outside in the winter to smoke, and more
money. Quick estimates indicate that since I stopped smoking in 1984, I have saved over
$50,000, based upon buying a pack per day at $4.00 per pack (quite conservative at today’s
costs) over the past 35 years. I quit when they became just over $1 per pack because that was
my financial limit, after starting when they cost about 60-65 cents. As the cost continues to
rise, the direct cost savings will be even higher. This does not include the associated health
costs, which can be staggering. If you smoke one pack per day and quit at $8/pack you will
have saved about $30,000 (not adjusted for increasing costs) in ten years. If you saved that
money instead, think about what you’d be able to buy. If you invested it in a stock portfolio
with an average return rate of 7.0% (which is not unreasonable in good times) over this 10
years, it would be worth over $41,000. If you did this for 20 years (still at $8/pack, with the
same return rate) you’d have about $123,000. Compound interest is amazing. Steadily
investing a little now, becomes a lot, many years from now.
Anyway, the best solution to the risks of smoking is to never start, and if you do smoke and
want to quit, then I suggest you do everything in your power to stop. If you choose to smoke,
then know the risks and the costs both to you and to others. Psychologists tell us that one of
the greatest influences on whether children begin to smoke or not is whether their parents
smoke.

50
Next week we will continue our studies of animal systems with an examination of
digestive & excretory systems.

51