The cardiovascular system; The respiratory system

The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume
fraction (EVF) is the proportion of blood volume that is occupied by red blood cells.

- hematocrit is independent of body size!!!

High blood pressure (hypertension)

Low blood pressure (hypotension)

The average heartbeat is 75 beats per minute.

Blood flow of the heart:

1) Beginning with the left ventricle, blood is pumped to the aorta via the
aortic valve

Note: The aorta is the largest blood vessel in the body, originating from
the left ventricle of the heart and bringing oxygenated
blood to all parts of the body in the systemic circulation.

a) the aorta has the highest BP in the body and then drops
from there until blood returns to the heart

Note: Blood pressure (BP) is the pressure (force per unit area)
exerted by circulating blood on the walls of blood
vessels, and constitutes one of the principal Vital
signs. The pressure of the circulating blood
decreases as it moves away from the heart through
arteries and capillaries, and toward the heart through
veins.

b) the left ventricle contracts with the most force to propel

blood through the systemic system

2) From the aorta, branch many smaller arteries, which themselves branch into
smaller arterioles, which branch into still smaller capillaries.

3) Blood from the capillaries are collected in the venules, which then collect
into larger veins, which collect again to the superior and inferior vena
cava.
 Note: A venule is a small blood vessel that allows deoxygenated blood to
return from the capillary beds to the larger blood vessels
called veins

4) The vena cava empties into the right atrium of the heart.

Note: Arteries and arterioles carry blood away from the heart while veins
and venules carry blood back to the heart.

This first half is called systemic circulation.

- Systemic circulation is the portion of the cardiovascular system

which carries oxygenated blood away from the heart, to the body, and
returns deoxygenated blood back to the heart.

5) From the right atrium, blood is squeezed into the right ventricle via the
tricuspid valve.

Note: The right atrium has a BP of almost zero thus it serves as an

ideal receptive area for the blood coming back to the
heart.

- if any area has a BP of zero blood will pool there.

6) The right ventricle then pumps blood through the pulmonary arteries via
the pulmonary valve, to arterioles, to capillaries in the lung.

Note: The pulmonary artery contains the most deoxygenated blood

in the body!!

7) The oxygenated blood then goes to the pulmonary veins leading to the heart
and empty into the left atrium via the mitrial (bicuspid) valve
 8) Left atrium then fills the left ventricle

This second half of circulation is called the pulmonary circulation.

- Pulmonary circulation is the portion of the cardiovascular system

which carries oxygen-depleted blood away from the heart, to the
lungs, and returns oxygenated blood back to the heart.

The heart muscle pumps the blood through the body by means of rhythmical contractions
(systole – ventricles contract) and relaxations or dilations (diastole – entire heart
relaxes and atria contract)!!!

The heart's left and right halves work almost synchronously (contract at the
same time), and they pump the same amount of blood aka same stroke
volume!!

When the ventricles contract (systole), the valves between the atria and the ventricles
close as the result of increasing pressure, and the valves to the pulmonary artery and the
aorta open. When the ventricles become flaccid during diastole, and the pressure
decreases, the reverse process takes place.
The rate of these contractions is controlled by the autonomic nervous
system but the autonomic nervous system doesn’t initiate the
contractions!!!

The Sinoatrial node (SA node), located in the right atrium, is the impulse generating
(pacemaker) tissue located in the right atrium of the heart. It contracts by itself at
regular intervals (it is autorythmic). It spreads its contractions to the surrounding
cardiac muscle via electrical synapse from gap junctions.

Recall: gaps junctions are small tunnels connecting cells that allow small
molecules and ions to move between cells

- Gap junctions provide the heart to spread the action potential from cell
to cell.

The pace of the SA node is faster than the normal heartbeats, but the parasympathetic,
vagus nerve innervates the SA node, slowing down the contractions and increases the
digestive activity in the intestines

The AV node is an area of specialized tissue between the atria (interatrial septa – wall
of cardiac muscle between the atria), which conducts the normal electrical impulse
from the atria to the ventricles.

The AV node is slower to contract, creating a delay which allows the atria to finish
their contraction, and to squeeze the contents into the ventricles before the
ventricles begin to contract.

From the AV node the action potential moves down conductive fibers called the bundle
of HIS. The bundle of His is located in the wall separating the ventricles.

The action potential then spreads out through the ventricular walls via conductive fibers
called Purkinje Fibers. From them, the action potential is spread through gap
junctions from one cardiac muscle to the next.

Purkinje fibers are located in the inner ventricular walls of the heart,
and allows for a more unified, and stronger contraction!!!
EKG
P wave: represents depolarization of both atria

The delay in the AV node forms much of the PR segment on the ECG. And part of
atrial repolarization can be represented by PR segment.

The QRS corresponds to the depolarization of the ventricles

T wave represents: ventricular repolarization

The T wave represents the repolarization (or recovery) of the ventricles. The interval
from the beginning of the QRS complex to the apex of the T wave is referred to as the
absolute refractory period. The last half of the T wave is referred to as the relative
refractory period (or vulnerable period).

Arteries

Arteries are elastic and stretch as they fill with blood. When the ventricles finish their
contraction, the stretched arteries recoil, keeping the blood moving more smoothly.
They are wrapped in smooth muscle that is typically innervated by the
sympathetic nervous system (“fight or flight”)!!

- Epinephrine is a powerful vasoconstrictor (and vasodilator for

skeletal muscle) causing arteries to constrict.

Larger arteries have less smooth muscle per volume than medium sized and are less
affected by the sympathetic nervous system. Under sympathetic stimulation some
medium sized arteries can reroute blood!!!
Arterioles are very small. They are wrapped by smooth muscle. Constriction and
dilation of arterioles can be used to regulate blood pressure as well as rerouting
blood.

Arteries carry blood away from the heart. The pulmonary artery contains the most
deoxygenated blood in the body!!

Capillaries

Capillaries are microscopic blood vessels whose cell walls are only one cell thick, and
the diameter is roughly equal to that of a red blood cell, therefore have the highest
resistance however.

- Nutrient and gas exchange with any tissue other than vascular tissue
takes place ONLY across capillary walls

There are four (4) methods for materials to cross capillary walls:

1) Pinocytosis (type of endocytosis, so ATP is involved)

2) diffusion or transport through capillary cell membranes

 3) movement through pores in the cells called fenestrations

4) movement through the space between the cells (intracellular cleft)

** Hydrostatic pressure forces fluid out of the circulatory system **

* Osmotic pressure forces the fluid back in to the capillaries and it stays the same *

As blood flows into a capillary, hydrostatic pressure is greater than osmotic pressure, and
the net fluid flow is out of the capillary, and into the interstitium. Although osmotic
pressure remains relatively constant throughout the capillary,
hydrostatic pressure drops from the arteriole end to the venule end.
Thus, osmotic pressure overcomes hydrostatic pressure near the venule end of a capillary,
and the net fluid flow is into the capillary and out of the interstitium.

The osmotic pressure in capillaries is greater towards, in comparison to hydrostatic

pressure, the venule end and the hydrostatic pressure is greater towards the arteriole
end.

- Remember osmotic pressure stays constant!!!

Capillaries have the greatest total cross-sectional area, and therefore

have the lowest velocity. Have the highest resistance however.

There is a 10% net loss of fluid to the interstitium because of this.

Veins and Venules

Venules and veins are similar in structure to arterioles and arteries.

- The lumen is larger than the lumen of comparable arteries, and veins
contain a far greater volume of blood. The total cross sectional
area of veins are about 4x as large as arteries.

- Veins, venules, and venus sinuses in the systemic circulation hold

about 64% of the blood in a body at rest, and act as a blood
reservoir for blood!!!

- Veins carry blood to the heart!!

 - Contraction of skeletal muscle helps blood move through
veins; however, the major propulsive force moving blood
through the veins is the pumping of the heart.

- Similar to the lymph system

Blood Flow and Bernoulli’s Equation

The total cross sectional area of veins are about 4x as large as arteries and therefore
have a smaller velocity according to the continuity equation, which blood flow follows,
from physics lecture 5:
Q = Av

The blood volume flow rate is approximately constant, the blood velocity is inversely
proportional to the cross-sectional area.

A1V1 = A2V2

The total cross-sectional area:

Capillaries > veins > arteries

Bernoulli's principle basically states that when the velocity of a fluid through a tube
increases, the pressure (more specifically, what is known as the fluid's 'gravitational
potential energy') decreases. That is pressure and kinetic energy are 'traded' for one
another in an ideal fluid flow system. This is essentially a type of conservation of energy.

Picture the following situation:

You have a tube that abruptly changes radius from a large radius to a small radius and an
ideal fluid is flowing from the large radius section to the small radius section. In this
situation, the fluid pressure of the fluid in the large radius part of the tube is actually
greater than the pressure in the small radius part of the tube. In addition, note that the
fluid velocity is higher in the small part of the tube than the large part of the tube.
Bernoulli's principle is basically saying that as a fluid's velocity goes up, it's fluid
pressure must go down, and as it's velocity goes down, it's fluid pressure must go
up. In essence, this is a form of conservation of energy; the increase in kinetic energy of
the fluid going from the large part of the tube to the small part of the tube occurs at the
expense of a drop in fluid pressure.

Okay so realizing that fact, now think about what is observed to happen in the blood
vessels.

As you go from the aorta to the capillaries, the cross-sectional area of the sum of the
tubes increases:

1) That is, the cross-sectional area of the capillaries summed together is far
greater than the cross-sectional area of the aorta.

2) Also remember that fluid velocity is higher in the aorta than in the
capillaries.

3) In addition, blood pressure is observed to decrease from the aorta to the

capillaries. That is, pressure decreases as you move toward the
veins.

But wait a minute...didn't we just say that Bernoulli's principle states that if the velocity
of a fluid were to decrease, that there must be a concurrent increase in the pressure of the
fluid? Doesn't that imply that pressure should increase as we move from the aorta (small
cross-sectional area) to the capillaries (large cross-sectional area)? Yes, that is Bernoulli's
principle. Hmmm...so what's wrong? This means that Bernoulli's principle is not satisfied
by the circulatory system!! But why?

It should be noted that Bernoulli's principle only really applies under some very ideal
conditions:

1) Non-turbulent flow
2) laminar flow
3) incompressible fluids
4) low mach numbers.

The cardiovascular system, however is not a laminar flow system, but rather a
pulsatile flow system (think beating heart), it also has many imperfect bifurcations
(branches) which cause turbulent flow, and also, its has particles in the fluid (Cells,
proteins, etc.) which are not a negligible size as the arteries branch off into smaller
and smaller tubes. In capillaries, the red blood cells can be the same width as the
capillary itself. In those situations, the fluid is no longer incompressible...heck some
would argue it's not even really a fluid. Thus, overall, Bernoulli's equation does not hold
for the circulatory system!

We can simplify Bernoulli's equation into two principles based on cross-sectional area:

1) "As Cross-sectional area increases, fluid velocity decreases”

2) "As Cross-sectional area increases, fluid pressure increases."
 For the cardiovascular system, the first one is true, and is seen in the continuity equation:
A1v1 = A2v2.

So blood velocity:

Capillaries < veins < arteries

The second part though, is not true. In fact, as we move from aorta (small cross-
sectional area, high velocity) to capillaries (large cross-sectional area, low velocity),
the pressure decreases. It does not increase! This is contradictory to Bernoulli's principle
for ideal fluids.

So you must be very careful when applying Bernoulli's principle to the cardiovascular
system. You must keep straight that the cardiovascular system, as a whole,
DOESN’T follow the ideal laws of fluid flow!

BP decreases as we go away from the heart and is the lowest in the

veins!!

Note: The pumping force of the heart is the major contributor to pressure in
the blood vessels. To compensate for the lower pressure, veins
have a valve system that prevents back flow of blood, however,
the major propulsive force moving blood through the veins is the
pumping of the heart.

←
← The veins can expand and narrow. When veins expand, more blood can be stored in
the veins and less blood returns to the heart for pumping into the arteries. As a
result, the heart pumps less blood, and blood pressure is lower. On the other hand,
when veins narrow, less blood is stored in the veins, more blood returns to the heart for
pumping into the arteries, and blood pressure is higher.

Or you can think of it like this: as blood vessels constrict, resistance

obviously goes up. That means the heart now has to pump the same
amount of blood against greater resistance, which means the heart has
to use more force which leads to greater pressure!!!

Blood pressure drops when:

1) arteries or arterioles dialate
2) heart function (i.e. heart rate) decrease
3) there is a decrease in blood volume.

However, the stroke volume of the heart is relatively constant in a person!!!

Note: In cardiovascular physiology, stroke volume (SV) is the volume of blood

pumped from one ventricle of the heart with each beat!!

Recall: The heart's left and right halves work almost synchronously (contract
at the same time), and they pump the same amount of blood.

- So the stroke volume is the same on the right half as it is on

the left half!!

Blood pressure is higher at feet than head because of gravity. This is why you can get
dizzy if you stand up too fast. Orthostatic hypotension resulting from decreased venous
return because the blood is pooled in your lower extremities.

Note: A heart attack diminishes the heart’s ability to pump blood, which
decreases the blood pressure!!

The Respiratory system

The respiratory system provides a path for gas exchange between the external
environment and the blood.

Inspiration occurs when the medulla oblongata of the midbrain signals the diaphragm
to contract.
 Recall: Medulla oblongata – Generates rhythmic breathing, regulates heart
rate and BP

The diaphragm is skeletal muscle, and innervated by the phrenic nerve

(somatic nervous system).

- Therefore uses acetylcholine as a neurotransmitter as well!!

Note: The phrenic nerver (somatic) carries signals from the medulla
oblongata to the diaphragm

- epinephrine would act as a vasodilator on this

When relaxed, the diaphragm is dome shaped. It flattens upon contraction, expanding
the chest cavity and creating negative gauge pressure (less than atmospheric pressure).
Intercostal muscles (rib muscles) also help to expand the chest cavity. Atmospheric
pressure forces air into the lungs. Upon relaxation of the diaphragm, the chest cavity
shrinks (aided by different intercostal muscles and abdomincal muscles), and the
elasticity of the lungs along with the increased pressure in the chest cavity forces air out
of the body.

Inspiration: Breathing/Inhalation

- always an active process

- caused my muscular contraction of:
a) diaphragm (phrenic nerver innverates this)
b) intercostal muscles (rib muscles)

- creates negative gauge pressure which forces air in

Expiration: Breathing out/Exhalation

- Occurs when the phrenic nerve ceases to send a signal to the

diaphragm
- Typically a passive process (no energy required)
- Mainly caused by:
a) elastic recoil of the diaphragm (when its relaxed its dome
shaped)
b) relaxation of the intercostal muscles
- The pressure in the lungs increases relative to the exterior and forces
air out

Note: The right lung is larger than the left lung.

Distention: The state of being distended, enlarged, swollen from internal
pressure!!

For example, on inhalation there is distention of the lungs due to the increased air
pressure within the lungs.

Air enters through the nose, moves through the (in order):

4) Pharynx
5) larynx
6) trachea
7) bronchi
8) broncioles
9) alveoli - where oxygen is exchange for carbon dioxide with the blood.

The nasal cavity is the space inside the nose:

- it filters, moistens, and warms incoming air!!

- Coarse hair at the front traps dust particles

- Mucus secreted by goblet cells also traps particles

Recall: Goblet cells secrete mucus to lubricate the intestine and

help protect the brush border from damage

- Capillaries within the nose warm the air

- Cilia move the mucus and dust to the back towards the pharynx, so
that it may be removed via spitting or swallowing.

The pharynx (or throat) functions as a passageway for food and air!!!

The larynx is the voice box!! It sits behind the epiglottis, which is a cartilaginous
member that prevents food from entering the trachea during swallowing!! When
nongaseous material enters the larynx, a coughing reflex is triggered forcing the
material back out. The larynx contains the vocal cords!!!

The trachea (or windpipe) lies in front of the esophagus.

 - It is composed of ringed cartilage (can’t constrict), covered by ciliated
mucous cells. Like the nasal cavity, the mucous and cilia in the trachea
collect dust and usher it toward the pharynx.

Note: Cartilage can’t constrict, it is avascular and receives nutrients via

simple diffusion!!

Before entering the lungs the trachea splits into right and left bronchi. Each bronchus
branches many more times to become tiny bronchioles, which are surrounded by
smooth muscle (Epinephrine would dilate/relax this). Bronchioles terminate in grape-
like clusters called alveolar sacs composed of tiny alveoli.

- From each alveolus, oxygen diffuses into a capillary where it is picked up

by red blood cells. The red blood cells release carbon dioxide, which
diffuses into the alveolus and is expelled on exhalation.

Erythrocytes are cells that contain hemoglobin and can carry oxygen to the blood.

- They have no organelles, but can perform glycolysis/fermentation

Since cilia are made of microtubules and cilia are found in the respiratory
tract, fallopian tube, and ependymal cells of the spinal cord, a problem in the
production of microtubules can result in breathing problems, infertility, and
poor circulation of cerebrospinal fluid!!!
Surfactant is a lipid molecule, produced by pneumocytes (lung cells), that decreases the
surface tension within the alveolar walls and prevents alveoli collapse. Alveolar
collapse would inhibit an effective exchange of air because it decreases the surface
area upon which gas exchange occurs.

The Chemistry of Gas Exchange

Typically we inspire about 79% nitrogen and 21% oxygen. Majority of air that we
inspire is nitrogen!!!

Inside the lungs, the partial pressure of oxygen is approximately 110 mm Hg and carbon
dioxide is approximately 40 mm Hg. Under these pressures, oxygen diffuses into the
capillaries, and carbon dioxide diffuses into the alveoli.

1 mm Hg = 1 torr
This diffusing is all possible because of the partial pressure
(concentration) differences on either side for a certain substance….a
concentration gradient!!!

98% of the oxygen in the blood binds rapidly and reversibly with the protein hemoglobin
inside the erythrocytes forming oxyhemoglobin.

- Deoxyhemoglobin is the form of hemoglobin without the bound oxygen.

Hemoglobin is composed of four polypeptide subunits, each with a single heme

cofactor (nonprotein component)!! The heme cofactor is an organic molecule with
an atom of iron at its center. Each of the four iron atoms in hemoglobin can bind
with one O2 molecule.

When one O2 molecule binds with an iron atom on hemoglobin, oxygenation of the other
heme group is accelerated. This is called homotropic activation.

- Homotropic activation- substrate serves as an activator, and You

achieved the typical S or sigmodical curve found in
describing behavior of enzymes such as hemoglobin.

Oxygen binds to the most difficult site first. This alters the conformation
of the protein so the next subunit binds oxygen more easily. This
process is then repeated for the other two subunits. This change in
conformation caused by the progressive binding of a ligand is known as
cooperativity and leads to sigmoid kinetics. The binding of one ligand
(substrate or modulator) changes the conformation of the protein. This
can increase or decrease the affinity for further ligands

Note: The release of oxygen by an of the heme groups also accelerates

the release of the others!!!

Myoglobin is a single-chain globular protein, containing a heme (iron-

containing porphyrin) prosthetic group in the center around which the
remaining apoprotein folds. Unlike the blood-borne hemoglobin, to which it is
structurally related, this protein does not exhibit cooperative binding of
oxygen.

Instead, the binding of oxygen by myoglobin is unaffected by the oxygen

pressure in the surrounding tissue!! Myoglobin is often cited as having an
"instant binding tenacity" to oxygen given its hyperbolic oxygen dissociation
curve. High concentrations of myoglobin in muscle cells allow organisms to hold
their breaths longer. It is found mainly in muscle tissue where it serves as an
intracellular storage site for oxygen!!

As O2 pressure increases, the O2 saturation of hemoglobin increases sigmoidally!!

The oxygen saturation of hemoglobin also depends upon CO2 pressure, [H+],
temperature of the blood, and [DPG].

The oxygen dissociation curve is a graph that shows the percent saturation of hemoglobin
at various partial pressures of oxygen.
Small fluctuations in oxygen pressure have little effect on certain areas of the graph.

The oxygen dissociation curve can shift based upon certain environmental changes such
as:
1) carbon dioxide pressure or DPG concentration
2) hydrogen ion concentration
3) temperature.

Note: If we increase [H+] (decrease pH), temperature, Pco2, or [DPG] then

hemoglobin affinity for oxygen decreases and unloading will
increase. The graph is shifted to the right

A shift to the right indicates a lowering of hemoglobin’s affinity to oxygen, which

will increase unloading.

A shift to the left indicates an increase of hemoglobin’s affinity to oxygen, which will
decrease unloading.

- Shift due to pH change is called Bohr shift!!

Carbon monoxide has more than 200 times greater affinity for oxygen than does
hemoglobin but shifts the curve to the left!!!
As blood moves through the system capillaries, where it can ONLY diffuse or change
concentration, oxygen diffuses from the blood to tissue, and carbon dioxide from tissue
(where it is created via Kreb cycle and pyruvate decarboxylation) to the blood.

- Gas exchange occurs by simple diffusion and the rate of simple

diffusion cant be increased because the concentration of
oxygen in the atmosphere remains constant!!

This diffusing is all possible because of the partial pressure differences on either side
for a certain substance

Carbon dioxide is carried through the blood in three (3) forms:

1) In physical solution

2) As bicarbonate ion

3) In carbamino compounds (combined with hemoglobin and other

proteins)

Bicarbonate ion is the most prevalent!!

The bicarbonate ion formation is governed by the enzyme carbonic anhydrase, which is
inside the red blood cell (erythrocyte).

- Because it is inside the cell, when carbon dioxide is released into the
lungs, bicarbonate ion diffuses into the cell to be changed into CO2.

- It will likely decrease the rate of gas exchange if we inhibit this enzyme.

Reaction catalyzed by carbonic anhydrase, IN TISSUES (HIGH CO2

CONCENTRATION), is:

Reaction catalyzed by carbonic anhydrase, IN LUNGS (LOW CO2

CONCENTRATION), is:

(in lungs and nephrons of the kidney - low CO2 concentration)

To balance the electrostatic forces when bicarbonate ion diffuse into the cell, to be
converted into CO2, chloride ions move out of the cell in a phenomenon called the
chloride shift!!!

Haldane Effect
Deoxygenation of the blood increases its ability to carry carbon dioxide; this property is
the Haldane effect, because it forms carbamino hemoglobin. Conversely, oxygenated
blood has a reduced capacity for carbon dioxide.

This is a consequence of the fact that reduced (deoxygenated) hemoglobin is a better

proton (hydrogen) acceptor than the oxygenated form, thus acts as a blood buffer.

In red blood cells, the enzyme carbonic anhydrase catalyzes the conversion of dissolved
carbon dioxide to carbonic acid, which rapidly dissociates to bicarbonate and a free
proton (hydrogen):
CO2 + H2O → H2CO3 → H+ + HCO3-

By Le Chatelier's principle, anything that stabilizes the proton produced will cause the
reaction to shift to the right, thus the enhanced affinity of deoxyhemoglobin for
protons enhances synthesis of bicarbonate and accordingly increases capacity of
deoxygenated blood for carbon dioxide

The general equation for the Haldane Effect is:

H+ + HbO2 ←→ H+.Hb + O2

So if we increase the oxyhemoglobin concentration we will subsequently

decrease the carbamino compound concentration!!!

Understand the connection between rate of breathing and carbon dioxide, pH, and oxygen
levels in the blood. For instance, in the case of acidosis, the body compensates
by increasing the breathing rate thereby expelling carbon dioxide and raising
the pH of the blood (this reduces bicarbonate and H+ in the blood).

Central Chemoreceptors:

- located in the medulla oblongata!!

- detect high levels of CO2 in the blood

Peripheral Chemoreceptors:
 - Located in the carotid arteries and the aorta
- Monitor CO2, O2 and H+ levels in the blood

A decrease in the arterial [O2] (hypoxia) will increase the rate of breathing
A high level of arterial [CO2] (hypercapnia) will also increase the rate of breathing

The nitrogen is extremely stable due to its strong triple bond. Thus, nitrogen
diffuses into the blood but doesn’t react with the chemicals in the blood.

The lymphatic system

The lymphatic system collects excess interstitial fluid and returns it to the blood.

Proteins and large particles that cannot be taken up by the capillaries are, removed
by the lymph system. The pathway to the blood takes the excess fluid through lymph
nodes which are well prepared to elicit an immune response if necessary. The lymph
system recycles the interstitial fluid and monitors the blood for infection. In
addition, the lymph system reroutes low soluble fat digestates around the small capillaries
of the intestine and into the large veins of the neck. Most tissues are drained via
lymphatic channels. A notable exception is the CNS!!!

Note: The CNS ISNT drained by the lymphatic system!!!

Because of starling forces, when blood flows through capillaries, the blood plasma
literally leaks out of the capillaries and into your tissues. This is the 'interstitial space'. No
RBCs leak through the capillaries, although WBCs do!! When this fluid exits your
capillaries it's in the 'interstitial space' and is called 'interstitial fluid'. Note that interstitial
fluid is the same thing as 'lymph', although technically this fluid isn't really 'lymph' until
it enters the lymphatic system. This is just an issue of nomenclature. When the blood
plasma leaks out of your circulatory system it comes in contact with all the cells of your
body. This is why you hear that cells are 'bathed' in lymph.

Lymph system is an open system, unlike the circulatory which is closed.

Now, the lymphatic system is a system of vessels much like our blood vessels except that
it is not 'circulatory' in nature. Remember that the blood vessels are continuous. If you
traced a line through a blood vessel you could travel round and round the circulatory
system ad infinitum. It's never ending, self-contained loop. The lymphatic system doesn't
work like that though. It's composed of 'terminal' vessels. If you traced a lymph vessel
from beginning to end you'd eventually exit the lymphatic system out into the
interstitial space (or into the circulatory system depending which way you're going).

In other words, fluid enters at one end and leaves at the other. Lymph capillaries are
like tiny fingers protruding into the tissues. To enter the lymph system, interstitial fluid
flows between overlapping endothelial cells. Larges particles literally push their
way between the cells into the lymph. Large particles CANNOT push
their way out.

When there is enough fluid in the 'interstitial' space, the lymphatic system will pick up
this fluid and return it to the circulation. I believe that the lymphatic system converges
around the level of your neck and then literally feeds back into the circulatory vessels.

Typically the interstitial fluid pressure is slightly negative (gauge pressure

wise). As the interstitial pressure rises toward zero, lymph flow increases!!!

Factors that affect interstitial pressure:

1) blood pressure
2) interstitial osmotic pressure
3) plasma osmotic pressure
4) permeability of capillaries

Remember that there is no 'pump' for the lymphatic system (like the heart). It
functions via a series of one-way valves, so fluid can only flow in one
direction, like in veins.

Recall: Veins also have these one way valve systems, and also work by skeletal
muscle contractions

So that means that as your muscles contract or you move around, you're squeezing the
lymph vessels in your body and causing the lymph to progress toward your neck.

Fluid is propelled in two (2) ways in the lymph system:

1) Smooth muscle in the walls of larger lymph vessels contract when

stretched
2) The lymph vessels maybe be squeezed by adjacent skeletal muscle
through body movement, arterial pulsations, etc..

This is why when you have been sitting down for a long time and not moving your feet,
your feet might get a little swollen. The swelling is the fluid that leaked from your
capillaries into the interstitial space of your feet. When you start wiggling your toes and
moving your feet around, you'll eventually push that fluid into your lymphatic system
through those one way ducts and up toward your neck. Therefore, Lymph flow in an
active individual is better than one in a resting individual.

Lymph from the right arm and head enter the blood via the right lymphatic duct, while
the rest of the body goes through the thoracic duct.
Lymph nodes contain large quantities of lymphocytes (agranular), which is
a type of white blood cell that can live for a long time.

The Blood

Blood is a connective tissue. Like any connective tissue, it contains cells and a matrix.

The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume
fraction (EVF) is the proportion of blood volume that is occupied by red blood cells.

Anemia is a condition where the RBC count decreases!!

Blood regulates the extracellular environment of the body by transporting nutrients,

waste products, hormones, and even heat.

Blood also protects the body from injury and foreign invaders.

Blood is composed of three (3) parts: the plasma, the buffy white coat (WBCs) and red
blood cells:

1) the plasma
- noncellular fluid which contains the matrix of blood, which
includes water, ions, urea, ammonia, proteins, and other organic and
inorganic compounds

- Important proteins in the plasma include: albumin, immunoglobins,

(antibodies) and clotting factors like fibrinogen and prothrombin
c) Albumins transport fatty acids and steroid and to regulate the
osmotic pressure of the blood

d) Fibrinogen, prothrombin, albumin and most plasma proteins

are made in the liver.

e) An important function of plasma proteins is to act

as a source of amino acids for tissue replacement!!

- ANTIBODIES (immunoglobulins) ARE PROTEINS and

are made in the lymph tissue by plasma cells NOT by the
liver!!

- Plasma in which the clotting protein fibrinogen is removed is

called serum
2) Leukocytes (white blood cells)

- do contain organelles, have a nucleus, but don’t contain

hemoglobin
- function to protect the body from foreign invaders
- Cant undergo mitosis

- There are two types of Leukocytes:

a) granular
i) fight general (nonspecific) infective agents
(part of innate immunity)!!!
ii) live a short time
iii) multiply quickly
iv) neutrophils, eosinophils, and basophils

neutrophils are neutral to acidic and basic dyes

eosinophils stain to acidic dyes
basophiles stain to basic dyes

b) agranular
i) work against specific agents of infection!!
ii) live a very long time
iii) monocytes, lymphocytes, megakaryocytes

Megakaryocytes stay mainly in the bone marrow

Monocytes become macrophages

- The most abundant leukocyte is the neutrophil!!

3) Erythrocytes (red blood cells)

- have no organelles (not even a nucleus)
- contain hemoglobin
- since there are no organelles, they only use anaerobic respiration
- don’t undergo mitosis or reproduce
- function is to transport oxygen and get rid of CO2
- spleen and liver destroys old worn out erythrocytes

Note: All blood cells are non-dividing!!

** ALL blood cells differentiate from the same type of precursor, a stem
cell residing in bone marrow **

Erythrocytes lose their nucleus in the marrow, and lose the rest of their organelles within
2-3 days of being released into the blood as reticulocytes.

Platelets are small portions of membrane-bound cytoplasm torn from megakaryocytes.

They function to aid in clotting a wound and DONT have a nucleus and AREN’T
cells!!

- They contain actin and myosin, residuals of the Golgi

and ER, mitochondria, and are capable of making
protaglandins and some important enzymes

- Its membrane is designed to avoid sticking to healthy endothelium

while sticking to injured endothelium. When they come into contact
with injured endothelium, they become sticky and begin to swell
releasing various chemicals and activating other platelets.

- The platelets stick to the endothelium and to each other forming a

loose platelet plug. Healthy individuals have many platelets in their
blood.

Coagulation involves many factors starting with Platelets and including the plasma
proteins prothrombin and fibrinogen.

It occurs in three steps:

1) a dozen or so coagulation factors form a complex called a protrombin
activator

2) Protrombin activator catalyzes the conversion of prothrombin, into thrombin

3) Thrombin is an enzyme that governs the polymerization of the plasma

protein fibrinogen to fibrin threads that attach to the platelets and form a
tight plug.

- So when coagulation occurs we have a decrease in fibrinogen

because it is being converted to fibrin!! We also see a decrease in
prothrombin because it is being converted into thrombin.

This blood clot formation appears relatively quick.

The following is the leukocyte composition in the blood:

 Neutrophils  62%
Lymphocytes  30%
Monocytes  5.3%
Eosinophils  2.3%  WORK AGAINST PARASITIC INFECTIONS
Basophils  0.4%  RELEASE CHEMICALS @ SITE OF
INFLAMATION

The Immune System

Consists of the thymus, lymph nodes, tonsils, and spleen!!

There are two types of immunity:

1) innate immunity – involves a generalized protection from most intruding
organisms and toxins.

- Innate immunity includes:

a) the skin barrier (relatively acidic)
b) stomach acid and digestive enzymes
c) phagocytic cells (granulocytes)
d) chemicals in the blood

Injury to tissue results in inflammation, which include dilation of blood vessels,

increased permeability of capillaries, swelling of tissue cells, and migration of
granulocytes and macrophages to the inflamed area.

- Histamine, prostaglandins, lymphokines are just some of

the causative agents of inflammation that are released by
tissue.

- part of the effect of inflammation is to ‘wall-off’ the effected tissue

and local lymph tissue vessels from the rest of the body, impeding
the spread of the infection

Infectious agents that are able to pass through the skin or the digestive defenses and enter
the body are first attacked by local macrophages. These phagocytotic giants can engulf
as many as 100 bacteria. Neutrophils are next on the scene. Most neutrophils are
stored in the bone marrow until needed, but some are found circulating
in the blood or in the tissues.

Neutrophils move toward the infected or injured areas, drawn by chemicals (a

process called chemotaxis) released from damaged tissue or by the infectious agents
themselves.
To enter into tissues, neutrophils slip between the endothelial cells of the
capillary walls, using an amaeboid-like process called diapedesis!!

Monocytes circulate in the blood until they, too, move into the tissues by diapedesis.
Once inside the tissues, monocytes mature to become macrophages.

When neutrophils and macrophages engulf necrotic tissue and bacteria they die.
These dead leukocytes, along with the tissue fluid and necrotic tissue, make up what is
known as pus.

Eosinophils work mainly against parasitic infections. Basophils release many of the
chemicals of the inflammation reaction.

2) acquired immunity – acquired immunity is protection against specific

organisms or toxins.

- Develops after the body is first attacked!!

- There are two types of acquired immunity:

a) humoral or B-cell immunity

I) promoted by B lymphocytes!!

II) Each B lymphocytes is capable of making a

SINGLE TYPE of antibody or
immunoglobulin (is a protein),
which it displays on its membrane

III) B lympocytes differentiate and mature in the

bone marrow and liver!!!

IIV) antibodies recognized a foreign particle called

an antigen, and are highly specific

V) The portion of the antigen that binds to the

antibody is called the antigenic
determinant. An antigenic determinant
that is removed that is removed from an
antigen is called a hapten.

VI) A hapten can only stimulate an immune

response if the individual has been
previously exposed to the full antigen.
 VII) If the B lymphocyte antibody contacts a
matching antigen (presented by the
macrophage), the B lymphocyte,
assisted by a Helper T cell,
differentiates into plasma cells and
memory B cells!!!

VIII) Plasma cells create antibodies (in the lymph

tissue) and then releases them to the
bloodstream

Free antibodies may attach their base to mast cells. When

an antibody whose base is bound to a mast cell
also binds to an antigen, the mast cell releases
histamine and other chemicals. When other free
antibodies contact the specific antigen, they bind to
it.

Once bound, the antibodies may begin a cascade of

reactions involving blood proteins (called
complement) that cause the antigen bearing cell
to be perforated. The antibodies may mark the antigen for
phagocytosis by macrophages and natural killer
cells.

The antibodies can cause antigenic substances to

agglutinate (unite as if by glue) or perforate the cell.

In the case of a toxin, the antibodies may block its

chemically active portion!!

First time immune response, to a new antigen, is called the

primary response. This requires 20 days to reach its full
potential.

Memory B cells proliferate and remain in the body!! In

the case of re-infection, each of these cells can be called
upon to synthesize antibodies, resulting in a faster response
and more potent affect called the secondary response.
Usually takes 5 days to reach its full potential

Humoral immunity is effective against bacteria, fungi,

parasitic protozoans, viruses, and blood toxins!!

b) cell mediated or T-cell immunity

 I) promoted by T lymphocytes

II) T-lymphocytes mature in the thymus!!

III) T-lymphocytes have an antibody-like protein on

their surface that recognizes antigens.
However, T-lymphocytes NEVER make
free antibodies.

IV) In the thymus, T-lymphocytes are tested against

self-antigens (antigens expressed by
normal cells of the body).

V) If the T-lympocyte binds to a self-antigen,

that T lymphocyte is destroyed. T
lymphocytes that aren’t
destroyed differentiate. (It will
suppress any T lymphocyte that
has a self-antigen)

VI) T-lymphocytes differentiate into:

1) helper T cells

- help B lymphocytes differentiate

and help in activating
killer T cells and
suppressor T cells

- are attacked by the HIV virus

2) memory T cells
- similar to memory B cells

3) suppressor T cells
- play a negative feedback role on
the immune system!!

4) killer T cells (aka cytotoxic T cells)

- punctures antigen-carrying cells

via the protein, perforin
 - can attack many cells because
they DONT phagocytize
their victims!!!

- responsible for fighting some forms

of cancer, and for attacking
transplanted tissue.

Cell-mediated immunity is effective against

infected cells!!

Lets imagine a bacterial infection. First we have inflammation. Macrophages, then

neutrophils, engulf bacteria. Interstitial fluid is flushed into the lymphatic system where
lymphocytes wait in the lymph nodes. Macrophages process and preserve the bacterial
antigens to B lymphocytes. With the help of Helper T cells, B lymphocytes differentiate
into memory cells and plasma cells. The memory cells are preparation in the event that
the same bacteria ever attack again (the secondary response). The plasma cells produce
antibodes, which are released into the blood to attack the bacteria.

Remember that a single antibody is specific for a single antigen, and that a
single B lymphocyte produces only one antibody type and T-lymphocytes cant
produce antibodies!!!

Blood Types

Blood types are identified by the A and B antigens on the surface of red blood cells.

For instance, type A blood means that the red blood cells have A antigens and doesn’t
have B antigens. Therefore it wont create antibodies for the A antigens, as in accordance
with cell mediated immunity, but will make B antibodies.

Type O has no A and B antigens and therefore is the universal donor, it makes A
and B antibodies.

Type AB is the universal receiver because it has both A and B antigens. And doesn’t
make A and B antibodies.

The genes which produce A and B antigens are co-dominant. Thus, an individual
having type A or B blood may be heterozygous or homozygous. An individual with type
O blood has two recessive alleles.

Note: An allele is one member of a pair or series of different forms of a gene

The IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB are
dominant over i, only ii people have type O blood (two recessive alleles). Individuals
with IAIA or IAi have type A blood, and individuals with IBIB or IBi have type B. IAIB
people have both phenotypes, because A and B express a special dominance relationship:
codominance, which means that type A and B parents can have an AB child. A type A
and a type B couple can also have a type O child if they are both heterozygous (IBi,IAi)

Note: A phenotype is any observable characteristic or trait of an organism:

such as its morphology, development, biochemical or physiological properties,
or behavior.

Note: Blood groups are inherited from both parents!!

Blood will attack another type of blood if it contains an antigen which the other type of
blood codes an antibody for.

Rh factors are surface proteins on red blood cells, probably ion channels.

- A negative type of blood doesn’t have these proteins and a positive

type of blood does have it.

Unlike the ABO antigens, the only ways antibodies are developed against the Rh
factor are through placental sensitization or transfusion. That is, if a person who is
Rh-negative has never been exposed to the Rh antigen, they do not possess the Rh
antibody.

There may be prenatal danger to the fetus when a pregnant woman is Rh-negative and the
biological father is Rh-positive. But, as discussed below, the situation is considerably
more complex than that. For the first preganancy, the mother is not exposed to fetal
blood until giving birth and problems are rare. Upon exposure, the mother develops an
immune response against the Rh-positive blood. In a second pregnancy, the second
fetus that is Rh-positive may be attacked by the antibodes of the mother, which are
small enough to pass through the placental barrier. The problem is life threatening,
and treatment usually involves complete replacement of the fetal blood with Rh-negative
blood for the first few weeks of life.

- Negative type of blood will attack a positive type of blood.