ANATOMY AND PHYSIOLOGY

Respiratory System, in anatomy and physiology, organs that deliver oxygen to

the circulatory system for transport to all body cells. Oxygen is essential for cells,
which use this vital substance to liberate the energy needed for cellular activities.
In addition to supplying oxygen, the respiratory system aids in removing of
carbon dioxide, preventing the lethal buildup of this waste product in body
tissues. Day-in and day-out, without the prompt of conscious thought, the
respiratory system carries out its life-sustaining activities. If the respiratory
system’s tasks are interrupted for more than a few minutes, serious, irreversible
damage to tissues occurs, followed by the failure of all body systems, and
ultimately, death.

While the intake of oxygen and removal of carbon dioxide are the primary

functions of the respiratory system, it plays other important roles in the body. The
respiratory system helps regulate the balance of acid and base in tissues, a
process crucial for the normal functioning of cells. It protects the body against
disease-causing organisms and toxic substances inhaled with air. The respiratory
system also houses the cells that detect smell, and assists in the production of
sounds for speech.

The respiratory and circulatory systems work together to deliver oxygen to

cells and remove carbon dioxide in a two-phase process called respiration. The
first phase of respiration begins with breathing in, or inhalation. Inhalation brings
air from outside the body into the lungs. Oxygen in the air moves from the lungs
through blood vessels to the heart, which pumps the oxygen-rich blood to all
parts of the body. Oxygen then moves from the bloodstream into cells, which
completes the first phase of respiration. In the cells, oxygen is used in a separate
energy-producing process called cellular respiration, which produces carbon
dioxide as a byproduct. The second phase of respiration begins with the
movement of carbon dioxide from the cells to the bloodstream. The bloodstream
carries carbon dioxide to the heart, which pumps the carbon dioxide-laden blood
to the lungs. In the lungs, breathing out, or exhalation, removes carbon dioxide
from the body, thus completing the respiration cycle.

STRUCTURE

The organs of the respiratory system extend from the nose to the lungs

and are divided into the upper and lower respiratory tracts. The upper respiratory
tract consists of the nose and the pharynx, or throat. The lower respiratory tract
includes the larynx, or voice box; the trachea, or windpipe, which splits into two
main branches called bronchi; tiny branches of the bronchi called bronchioles;
and the lungs, a pair of saclike, spongy organs. The nose, pharynx, larynx,
trachea, bronchi, and bronchioles conduct air to and from the lungs. The lungs
interact with the circulatory system to deliver oxygen and remove carbon dioxide.

NASAL
PASSAGES
Anatomy of the Nose
The uppermost
portion of the human
respiratory system,
the nose is a hollow air passage that functions in breathing and in the sense of
smell. The nasal cavity moistens and warms incoming air, while small hairs and
mucus filter out harmful particles and microorganisms.
 The flow of air from outside of the body to the lungs begins with the nose,
which is divided into the left and right nasal passages. The nasal passages are
lined with a membrane composed primarily of one layer of flat, closely packed
cells called epithelial cells. Each epithelial cell is densely fringed with thousands
of microscopic cilia, fingerlike extensions of the cells. Interspersed among the
epithelial cells are goblet cells, specialized cells that produce mucus, a sticky,
thick, moist fluid that coats the epithelial cells and the cilia. Numerous tiny blood
vessels called capillaries lie just under the mucous membrane, near the surface
of the nasal passages. While transporting air to the pharynx, the nasal passages
play two critical roles: they filter the air to remove potentially disease-causing
particles; and they moisten and warm the air to protect the structures in the
respiratory system.

Filtering prevents airborne bacteria, viruses, other potentially disease-

causing substances from entering the lungs, where they may cause infection.
Filtering also eliminates smog and dust particles, which may clog the narrow air
passages in the smallest bronchioles. Coarse hairs found just inside the nostrils
of the nose trap airborne particles as they are inhaled. The particles drop down
onto the mucous membrane lining the nasal passages. The cilia embedded in the
mucous membrane wave constantly, creating a current of mucus that propels the
particles out of the nose or downward to the pharynx. In the pharynx, the mucus
is swallowed and passed to the stomach, where the particles are destroyed by
stomach acid. If more particles are in the nasal passages than the cilia can
handle, the particles build up on the mucus and irritate the membrane beneath it.
This irritation triggers a reflex that produces a sneeze to get rid of the polluted air.

The nasal passages also moisten and warm air to prevent it from

damaging the delicate membranes of the lung. The mucous membranes of the
nasal passages release water vapor, which moistens the air as it passes over the
membranes. As air moves over the extensive capillaries in the nasal passages, it
is warmed by the blood in the capillaries. If the nose is blocked or “stuffy” due to
a cold or allergies, a person is forced to breathe through the mouth. This can be
potentially harmful to the respiratory system membranes, since the mouth does
not filter, warm, or moisten air.

In addition to their role in the respiratory system, the nasal passages

house cells called olfactory receptors, which are involved in the sense of smell.
When chemicals enter the nasal passages, they contact the olfactory receptors.
This triggers the receptors to send a signal to the brain, which creates the
perception of smell.

PHARYNX

Air leaves the nasal passages and flows to the pharynx, a short, funnel-

shaped tube about 13 cm (5 in) long that transports air to the larynx. Like the
nasal passages, the pharynx is lined with a protective mucous membrane and
ciliated cells that remove impurities from the air. In addition to serving as an air
passage, the pharynx houses the tonsils, lymphatic tissues that contain white
blood cells. The white blood cells attack any disease-causing organisms that
escape the hairs, cilia, and mucus of the nasal passages and pharynx. The
tonsils are strategically located to prevent these organisms from moving further
into the body. One tonsil, called the adenoids, is found high in the rear wall of the
pharynx. A pair of tonsils, the palatine tonsils, is located at the back of the
pharynx on either side of the tongue. Another pair, the lingual tonsils, is found
deep in the pharynx at the base of the tongue. In their battles with disease-
causing organisms, the tonsils sometimes become swollen with infection. When
the adenoids are swollen, they block the flow of air from the nasal passages to
the pharynx, and a person must breathe through the mouth.

LARYNX

Air moves from the pharynx to the larynx, a structure about 5 cm (2 in)

long located approximately in the middle of the neck. Several layers of cartilage,
a tough and flexible tissue, comprise most of the larynx. A protrusion in the
cartilage called the Adam’s apple sometimes enlarges in males during puberty,
creating a prominent bulge visible on the neck.

While the primary role of the larynx is to transport air to the trachea, it also

serves other functions. It plays a primary role in producing sound; it prevents
food and fluid from entering the air passage to cause choking; and its mucous
membranes and cilia-bearing cells help filter air. The cilia in the larynx waft
airborne particles up toward the pharynx to be swallowed.

Food and fluids from the pharynx usually are prevented from entering the

larynx by the epiglottis, a thin, leaflike tissue. The “stem” of the leaf attaches to
the front and top of the larynx. When a person is breathing, the epiglottis is held
in a vertical position, like an open trap door. When a person swallows, however,
a reflex causes the larynx and the epiglottis to move toward each other, forming
a protective seal, and food and fluids are routed to the esophagus. If a person is
eating or drinking too rapidly, or laughs while swallowing, the swallowing reflex
may not work, and food or fluid can enter the larynx. Food, fluid, or other
substances in the larynx initiate a cough reflex as the body attempts to clear the
larynx of the obstruction. If the cough reflex does not work, a person can choke,
a life-threatening situation. The Heimlich maneuver is a technique used to clear a
blocked larynx (see First Aid). A surgical procedure called a tracheotomy is used
to bypass the larynx and get air to the trachea in extreme cases of choking.

TRACHEA, BRONCHI, BRONCHIOLES

Air passes from the larynx into the trachea, a tube about 12 to 15 cm

(about 5 to 6 in) long located just below the larynx. The trachea is formed of 15 to
20 C-shaped rings of cartilage. The sturdy cartilage rings hold the trachea open,
enabling air to pass freely at all times. The open part of the C-shaped cartilage
lies at the back of the trachea, and the ends of the “C” are connected by muscle
tissue.
 The base of the trachea is located a little below where the neck meets the
trunk of the body. Here the trachea branches into two tubes, the left and right
bronchi, which deliver air to the left and right lungs, respectively. Within the
lungs, the bronchi branch into smaller tubes called bronchioles. The trachea,
bronchi, and the first few bronchioles contribute to the cleansing function of the
respiratory system, for they, too, are lined with mucous membranes and ciliated
cells that move mucus upward to the pharynx.

Human Lungs
In humans the lungs occupy a large portion of the chest cavity from the
collarbone down to the diaphragm. The right lung is divided into three sections,
or lobes. The left lung, with a cleft to accommodate the heart, has only two lobes.
The two branches of the trachea, called bronchi, subdivide within the lobes into
smaller and smaller air vessels known as bronchioles. Bronchioles terminate in
alveoli, tiny air sacs surrounded by capillaries. When the alveoli inflate with
inhaled air, oxygen diffuses into the blood in the capillaries to be pumped by the
heart to the tissues of the body. At the same time carbon dioxide diffuses out of
the blood into the lungs, where it is exhaled.

The bronchioles divide many more times in the lungs to create an

impressive tree with smaller and smaller branches, some no larger than 0.5 mm
(0.02 in) in diameter. These branches dead-end into tiny air sacs called alveoli.
The alveoli deliver oxygen to the circulatory system and remove carbon dioxide.
Interspersed among the alveoli are numerous macrophages, large white blood
cells that patrol the alveoli and remove foreign substances that have not been
filtered out earlier. The macrophages are the last line of defense of the
respiratory system; their presence helps ensure that the alveoli are protected
from infection so that they can carry out their vital role.

Alveoli

A scanning electron micrograph reveals the tiny sacs known as alveoli

within a section of human lung tissue. Human beings have a thin layer of about
700 million alveoli within their lungs. This layer is crucial in the process called
respiration, exchanging oxygen and carbon dioxide with the surrounding blood
capillaries.
CNRI/Photo Researchers, Inc.

The alveoli number about 150 million per lung and comprise most of the

lung tissue. Alveoli resemble tiny, collapsed balloons with thin elastic walls that
expand as air flows into them and collapse when the air is exhaled. Alveoli are
arranged in grapelike clusters, and each cluster is surrounded by a dense hairnet
of tiny, thin-walled capillaries. The alveoli and capillaries are arranged in such a
way that air in the wall of the alveoli is only about 0.1 to 0.2 microns from the
blood in the capillary. Since the concentration of oxygen is much higher in the
alveoli than in the capillaries, the oxygen diffuses from the alveoli to the
capillaries. The oxygen flows through the capillaries to larger vessels, which
carry the oxygenated blood to the heart, where it is pumped to the rest of the
body.

Carbon dioxide that has been dumped into the bloodstream as a waste

product from cells throughout the body flows through the bloodstream to the
heart, and then to the alveolar capillaries. The concentration of carbon dioxide in
the capillaries is much higher than in the alveoli, causing carbon dioxide to
diffuse into the alveoli. Exhalation forces the carbon dioxide back through the
respiratory passages and then to the outside of the body.

REGULATION

Diaphragm and Respiration

As the diaphragm contracts and moves downward, the pectoralis minor
and intercostal muscles pull the rib cage outward. The chest cavity expands, and
air rushes into the lungs through the trachea to fill the resulting vacuum. When
the diaphragm relaxes to its normal, upwardly curving position, the lungs
contract, and

The flow of air in and out of the lungs is controlled by the nervous system,

which ensures that humans breathe in a regular pattern and at a regular rate.
Breathing is carried out day and night by an unconscious process. It begins with
a cluster of nerve cells in the brain stem called the respiratory center. These cells
send simultaneous signals to the diaphragm and rib muscles, the muscles
involved in inhalation. The diaphragm is a large, dome-shaped muscle that lies
just under the lungs. When the diaphragm is stimulated by a nervous impulse, it
flattens. The downward movement of the diaphragm expands the volume of the
cavity that contains the lungs, the thoracic cavity. When the rib muscles are
stimulated, they also contract, pulling the rib cage up and out like the handle of a
pail. This movement also expands the thoracic cavity. The increased volume of
the thoracic cavity causes air to rush into the lungs. The nervous stimulation is
brief, and when it ceases, the diaphragm and rib muscles relax and exhalation
occurs. Under normal conditions, the respiratory center emits signals 12 to 20
times a minute, causing a person to take 12 to 20 breaths a minute. Newborns
breathe at a faster rate, about 30 to 50 breaths a minute.

The rhythm set by the respiratory center can be altered by conscious

control. The breathing pattern changes when a person sings or whistles, for
example. A person also can alter the breathing pattern by holding the breath. The
cerebral cortex, the part of the brain involved in thinking, can send signals to the
diaphragm and rib muscles that temporarily override the signals from the
respiratory center. The ability to hold one’s breath has survival value. If a person
encounters noxious fumes, for example, it is possible to avoid inhaling the fumes.

A person cannot hold the breath indefinitely, however. If exhalation does

not occur, carbon dioxide accumulates in the blood, which, in turn, causes the
blood to become more acidic. Increased acidity interferes with the action of
enzymes, the specialized proteins that participate in virtually all biochemical
reaction in the body. To prevent the blood from becoming too acidic, the blood is
monitored by special receptors called chemoreceptors, located in the brainstem
and in the blood vessels of the neck. If acid builds up in the blood, the
chemoreceptors send nervous signals to the respiratory center, which overrides
the signals from the cerebral cortex and causes a person to exhale and then
resume breathing. These exhalations expel the carbon dioxide and bring the
blood acid level back to normal.

A person can exert some degree of control over the amount of air inhaled,

with some limitations. To prevent the lungs from bursting from overinflation,
specialized cells in the lungs called stretch receptors measure the volume of air
in the lungs. When the volume reaches an unsafe threshold, the stretch
receptors send signals to the respiratory center, which shuts down the muscles
of inhalation and halts the intake of air.

IMMUNITY
Immunology is the study of our protection from foreign macromolecules or
invading organisms and our responses to them. These invaders include viruses,
bacteria, protozoa or even larger parasites. In addition, we develop immune
responses against our own proteins (and other molecules) in autoimmunity and
against our own aberrant cells in tumor immunity (Tortora, et al., 2006).
Our first line of defense against foreign organisms are barrier tissues such
as the skin that stop the entry of organism into our bodies. If, however, these
barrier layers are penetrated, the body contains cells that respond rapidly to the
presence of the invader. These cells include macrophages and neutrophils that
engulf foreign organisms and kill them without the need for antibodies. Immediate
challenge also comes from soluble molecules that deprive the invading organism
of essential nutrients (such as iron) and from certain molecules that are found on
the surfaces of epithelia, in secretions (such as tears and saliva) and in the blood
stream. This form of immunity is the innate or non-specific immune system that is
continually ready to respond to invasion.
A second line of defense is the specific or adaptive immune system which
may take days to respond to a primary invasion (that is infection by an organism
that has not hitherto been seen). In the specific immune system, we see the
production of antibodies (soluble proteins that bind to foreign antigens) and cell-
mediated responses in which specific cells recognize foreign pathogens and
destroy them. In the case of viruses or tumors, this response is also vital to the
recognition and destruction of virally-infected or tumorigenic cells. The response
to a second round of infection is often more rapid than to the primary infection
because of the activation of memory B and T cells. We shall see how cells of the
immune system interact with one another by a variety of signal molecules so that
a coordinated response may be mounted. These signals may be proteins such
as lymphokines which are produced by cells of the lymphoid system, cytokines
and chemokines that are produced by other cells in an immune response, and
which stimulate cells of the immune system. The immune system is composed
of two major subdivisions, the innate or nonspecific immune system and the
adaptive or specific immune system. The innate immune system is our first line of
defense against invading organisms while the adaptive immune system acts as a
second line of defense and also affords protection against re-exposure to the
same pathogen. Each of the major subdivisions of the immune system has both
cellular and humoral components by which they carry out their protective
function. In addition, the innate immune system also has anatomical features that
function as barriers to infection. Although these two arms of the immune system
have distinct functions, there is interplay between these systems (i.e.,
components of the innate immune system influence the adaptive immune system
and vice versa).
Although the innate and adaptive immune systems both function to protect
against invading organisms, they differ in a number of ways. The adaptive
immune system requires some time to react to an invading organism, whereas
the innate immune system includes defenses that, for the most part, are
constitutively present and ready to be mobilized upon infection. Second, the
adaptive immune system is antigen specific and reacts only with the organism
that induced the response. In contrast, the innate system is not antigen specific
and reacts equally well to a variety of organisms. Finally, the adaptive immune
system demonstrates immunological memory. It “remembers” that it has
encountered an invading organism and reacts more rapidly on subsequent
exposure to the same organism. In contrast, the innate immune system does not
demonstrate immunological memory.
All cells of the immune system have their origin in the bone marrow and
they include myeloid (neutrophils, basophils, eosinpophils, macrophages and
dendritic cells) and lymphoid (B lymphocyte, T lymphocyte and Natural Killer)
cells , which differentiate along distinct pathways. The myeloid progenitor (stem)
cell in the bone marrow gives rise to erythrocytes, platelets, neutrophils,
monocytes/macrophages and dendritic cells whereas the lymphoid progenitor
(stem) cell gives rise to the NK, T cells and B cells. For T cell development the
precursor T cells must migrate to the thymus where they undergo differentiation
into two distinct types of T cells, the CD4+ T helper cell and the CD8+ pre-
cytotoxic T cell. Two types of T helper cells are produced in the thymus the TH1
cells, which help the CD8+ pre-cytotoxic cells to differentiate into cytotoxic T
cells, and TH2 cells, which help B cells, differentiate into plasma cells, which
secrete antibodies.
The main function of the immune system is self/non-self discrimination.
This ability to distinguish between self and non-self is necessary to protect the
organism from invading pathogens and to eliminate modified or altered cells (e.g.
malignant cells). Since pathogens may replicate intracellularly (viruses and some
bacteria and parasites) or extracellularly (most bacteria, fungi and parasites),
different components of the immune system have evolved to protect against
these different types of pathogens. It is important to remember that infection with
an organism does not necessarily mean diseases, since the immune system in
most cases will be able to eliminate the infection before disease occurs. Disease
occurs only when the bolus of infection is high, when the virulence of the
invading organism is great or when immunity is compromised. Although the
immune system, for the most part, has beneficial effects, there can be
detrimental effects as well. During inflammation, which is the response to an
invading organism, there may be local discomfort and collateral damage to
healthy tissue as a result of the toxic products produced by the immune
response. In addition, in some cases the immune response can be directed
toward self tissues resulting in autoimmune disease.

NON-SPECIFIC IMMUNITY

The elements of the non-specific (innate) immune system include anatomical

barriers, secretory molecules and cellular components. Among the mechanical
anatomical barriers are the skin and internal epithelial layers, the movement of the
intestines and the oscillation of broncho-pulmonary cilia. Associated with these
protective surfaces are chemical and biological agents.

A. Anatomical barriers to infections

1. Mechanical factors

The epithelial surfaces form a physical barrier that is very impermeable to most
infectious agents thus, the skin acts as our first line of defense against invading
organisms. The desquamation of skin epithelium also helps remove bacteria and other
infectious agents that have adhered to the epithelial surfaces. Movement due to cilia or
peristalsis helps to keep air passages and the gastrointestinal tract free from
microorganisms. The flushing action of tears and saliva helps prevent infection of the
eyes and mouth. The trapping effect of mucus that lines the respiratory and
gastrointestinal tract helps protect the lungs and digestive systems from infection.

2. Chemical factors

Fatty acids in sweat inhibit the growth of bacteria. Lysozyme and phospholipase found in
tears, saliva and nasal secretions can breakdown the cell wall of bacteria and destabilize
bacterial membranes. The low pH of sweat and gastric secretions prevents growth of
bacteria. Defensins found in the lung and gastrointestinal tract have antimicrobial
activity. Surfactants in the lung act as opsonins (substances that promote phagocytosis
of particles by phagocytic cells).

3. Biological factors

The normal flora of the skin and in the gastrointestinal tract can prevent the
colonization of pathogenic bacteria by secreting toxic substances or by competing with
pathogenic bacteria for nutrients or attachment to cell surfaces.

B. Humoral barriers to infection

The anatomical barriers are very effective in preventing colonization of tissues by

microorganisms. However, when there is damage to tissues the anatomical barriers are
breached and infection may occur. Once infectious agents have penetrated tissues,
another innate defense mechanism comes into play, namely acute inflammation.
Humoral factors play an important role in inflammation, which is characterized by edema
and the recruitment of phagocytic cells. These humoral factors are found in serum or
they are formed at the site of infection.

The complement system is the major humoral non-specific defense mechanism.

Once activated complement can lead to increased vascular permeability,
recruitment of phagocytic cells, and lysis and opsonization of bacteria.
Coagulation system, depending on the severity of the tissue injury, the
coagulation system may or may not be activated. Some products of the
coagulation system can contribute to the non-specific defenses because of their
ability to increase vascular permeability and act as chemotactic agents for
phagocytic cells. In addition, some of the products of the coagulation system are
directly antimicrobial. For example, beta-lysin, a protein produced by platelets
during coagulation can lyse many Gram positive bacteria by acting as a cationic
detergent. Lactoferrin and transferrin binds with iron, an essential nutrient for
bacteria, these proteins limit bacterial growth. Interferons are proteins that can
limit virus replication in cells. Lysozyme breaks down the cell wall of bacteria.
Interleukin-1 induces fever and the production of acute phase proteins, some of
which are antimicrobial because they can opsonize bacteria.

 Cellular barriers to infection

Part of the inflammatory response is the recruitment of polymorphonuclear

eosinophiles and macrophages to sites of infection. These cells are the main line
of defense in the non-specific immune system.

Polymorphonuclear cells are recruited to the site of infection where they

phagocytose invading organisms and kill them intracellularly. In addition, PMNs
contribute to collateral tissue damage that occurs during inflammation.

Tissue macrophages and newly recruited monocytes, which differentiate into

macrophages, also function in phagocytosis and intracellular killing of microorganisms.
In addition, macrophages are capable of extracellular killing of infected or altered self
target cells. Furthermore, macrophages contribute to tissue repair and act as antigen-
presenting cells, which are required for the induction of specific immune responses.

Natural killer (NK) and lymphokine activated killer (LAK) cells can nonspecifically
kill virus infected and tumor cells. These cells are not part of the inflammatory response
but they are important in nonspecific immunity to viral infections and tumor surveillance.
Eosinophils have proteins in granules that are effective in killing certain parasites.