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The Respiratory System
Lecture 11th (11th-15th February 2018)
The respiratory is a biological system consisting of specific organs and structures used
for the process of respiration. It is involved in the intake and exchange of oxygen (O2)
and carbon dioxide (CO2) between body and the environment. Respiration, takes place
in the respiratory organs called lungs. The passage of air into the lungs to supply the
body with O2 is known as inhalation, and the passage of air out of the lungs to expel
carbon dioxide (CO2) is known as exhalation; this process is collectively
called breathing or ventilation. The anatomical features of the respiratory system
include: (1). trachea; (2). bronchi; (3). bronchioles; (4). lungs, and (5). diaphragm.
Molecules of O2 and CO2 are passively exchanged, by diffusion, between the gaseous
external environment and the blood. This exchange process occurs in the alveoli (air
sacs) in the lung via the process of osmosis.

(Fig. 1): Anatomy of the respiratory system of human

The conducting portion is made up of: (1). Nostrils and nasal cavities; (2).
Nasopharynx; (3). Larynx; (4). Trachea; (5). bronchii and (6). bronchioles. The
trachea branches to give rise to two primary (main) bronchii. These then branch
successively to give rise, in turn, to secondary and tertiary bronchii. These then
branch to give rise to several orders of progressively smaller airways called
bronchioles, the smallest of which are called terminal bronchioles. These are the
last components of the conducting portion of the respiratory system. Terminal
bronchioles give rise to respiratory bronchioles, which ultimately lead to the alveoli.
The respiratory tract is divided into the upper airways and lower airways. The upper
respiratory tract can refer to the parts of the respiratory system lying above the sternal
angle (outside of the thorax), above the vocal folds, or above the cricoid
cartilage. The larynx is sometimes included in both the upper and lower airways. The
larynx is also called the voice box and has the associated cartilage that produces
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sound. The tract consists of the nasal cavity and paranasal sinuses, the pharynx 

(nasopharynx,  oropharynx and laryngopharynx) and sometimes includes the larynx.
The lower respiratory tract is derived from the developing foregut and consists of
the trachea, bronchi (primary, secondary and tertiary),  bronchioles  (including
terminal and respiratory), and lungs (including alveoli) [Fig. 2a & 2b]. It also
sometimes includes the larynx. The lungs can be included in the lower respiratory
tract or as separate entity and include the respiratory bronchioles, alveolar
ducts, alveolar sacs, and alveoli. The respiratory tract can also be divided into
a conducting zone and a respiratory zone, based on the distinction of transporting
gases versus exchanging them. From the bronchi, the dividing tubes become
progressively smaller with an estimated 20 to 23 divisions before ending at an
alveolus.

(Fig. 2a & 2b): (a). The Anatomy of upper and lower respiratory tract; (b).
Parts of conducting portions (respiratory tree) of the respiratory system.
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(Fig. 3a & 3b): (a). Schematic drawing as CS of trachea to demonstrate its main
components. (b). The respiratory tree: (1). Trachea; (2). Mainstem bronchus; (3). Lobar
bronchus; (4). Segmental bronchus; (5). Bronchiole; (6). Alveolar duct and (7). Alveolus.

Trachea:
The trachea is the largest tube in the respiratory tract and consists of tracheal
rings of hyaline cartilage. The trachea is a wide flexible tube, the lumen of which is
kept open by 20 tracheal cartilages, which are C-shaped rings of hyaline cartilage.
The gaps between the rings of cartilage are filled by the trachealis muscle- a bundle of
smooth muscle, and fibroelastic tissue (Figs. 1 and 3). Together these hold the lumen
of the trachea open, but allow flexibility during inspiration and expiration. The
respiratory mucosa and submucosa are adapted to warm and moisten the air, and to
trap particles in mucous. The trachea branches off into two bronchial tubes, a left and
a right main or primary bronchus. The bronchi branch off into smaller sections
inside the lungs, called bronchioles. These bronchioles give rise to the air sacs in the
lungs called the alveoli. The respiratory tree or trachea-bronchial tree is a term
also used to refer to the branching structure of airways supplying air to the lungs and
includes the trachea, bronchi and bronchioles. In the tertiary bronchii, there is less
cartilage, and it does not completely encircle the lumen, as shown diagramatically
beloow [Fig. 5]. Note also how the mucosa is folded, and think about how this might
change as you breathe in and out.
Mucosa and sub-mucosa of Trachea:
The respiratory mucosa is made up of the epithelium and supporting lamina
propria) (Fig. 4a & 4b). The epithelium is tall columnar pseudostratified with
cilia and goblet cells. The supporting lamina propria underneath the epithelium
contains elastin, that plays a role in the elastic recoil of the trachea during
inspiration and expiration, together with blood vessels that warm the air.
The sub-mucosa contains glands which are mixed sero-mucous glands. The
watery secretions from the serous glands humidify the inspired air. The mucous,
together with mucous from the goblet cells traps particles from the air which are
transported upwards towards the pharynx by the cilia on the epithlium. This helps
to keep the lungs free of particles and bacteria.

(Fig -4 a&b): (a). A CS through the trachea, shows the major layers. (b). A higher power
image of the trachea showing the glands and epithelium in more detail. Note the
numerous sero-mucous glands in the submucosa layer. The layer of cartilage is not seen
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here, but instead there is a layer of fibro-elastic Co.T. which runs between the rings of
cartilage.

(Fig-5 a&b): (a). A CS of a tertiary bronchus. Compare this picture with that of the
trachea: Can you identify the circular layer of smooth muscle, and the cartilage, and
some glands in the submucosa? The smooth muscle is used to control the diameter and
length of the bronchii which contracts during expiration to help expel the air. There is
also lots of elastin present in the submucosa, as in the trachea. The epithelium is now tall
columnar, not pseudostratified (difficult to see at this magnification) and has very few
goblet cells.

The tertiary bronchii branch into bronchioles, which have a diameter of 1mm or less,
and the wall structure changes. The epithelium is made up of ciliated columnar cells
in larger bronchioles, or non-ciliated in smaller bronchioles (difficult to see at low
magnification). There are no goblet cells, but there are cells called Clara cells. These
cells are secretory - they secrete one of the components of surfactant.

Bronchioles:
Bronchial anatomy:
A typical pair of human lungs contain about 700 million alveoli, producing 70-75
m2 of surface area. Each alveolus is wrapped in a fine mesh of capillaries covering
about 70% of its area. An adult alveolus has an average diameter of 200
micrometres, with an increase in diameter during inhalation.

(Fig -6 a&b): (a). A CS of a bronchiole where there is neither cartilage nor glands. Can
you identify the ring of smooth muscle, which is arranged in discrete bundles with a
variety of organizations.
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Terminal Bronchiole:
The final branches of the bronchioles are called terminal bronchioles. These have a
layer smooth muscle surrounding their lumens [Fig.6a & 6b]. Stimulation of the vagus
nerve (parasympathetic) causes the smooth muscle to contract, and reduce the
diameter of the terminal bronchioles.
Small sacs are found extending from the walls of the terminal bronchii called
respiratory bronchioles (R), that are lined by a ciliated cuboidal epithelium, and some
non-ciliated cells called clara cells (Fig. 7).
Asthma: because the diameter of the bronchioles is reliant on smooth muscle tone,
these airways can almost completely shut if the smooth muscles contract strongly,
which can happen in an asthmatic attack.
The lungs:
The lungs are the largest organs in the lower respiratory tract. They are suspended
within the pleural cavity of the thorax. The pleurae are two thin membranes, one cell
layer thick, which surround the lungs. The inner (visceral pleura) covers the lungs
and the outer (parietal pleura) lines the inner surface of the chest wall. This
membrane secretes a small amount of fluid, allowing the lungs to move freely within
the pleural cavity while expanding and contracting during breathing. The lungs are
divided into different lobes. The right lung is larger in size than the left, because of
the heart's being situated to the left of the midline. The right lung has three lobes i.e.
upper, middle, and lower (or superior, middle and inferior), and the left lung has two
i.e. upper and lower (or superior and inferior), plus a small tongue-shaped portion of
the upper lobe known as the lingula. Each lobe is further divided up into segments
called bronchopulmonary segments. Each lung has a costal surface, which is
adjacent to the ribcage; a diaphragmatic surface, which faces downward toward the
diaphragm; and a mediastinal surface, which faces toward the center of the chest, and
lies against the heart, great vessels, and the carina where the two mainstem bronchi
branch off from the base of the trachea. The lungs are made up of 13 different kinds
of cells, 11 types of epithelial cell and 2 types of mesenchymal cell. The epithelial
cells form the lining of the tracheal, and bronchial tubes, while the mesenchymal cells
line the lungs. The respiratory tract is covered in epithelium, which varies down the
tract. There are glands  and  mucus produced by goblet cells in parts, as well
as smooth muscle, elastin or cartilage.

(Fig. 7a&b): A terminal bronchiole (TB) at a lower magnification than the 3 pictures

above which represents the conducting portion of the respiratory system, and has the
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smallest diameter of all (< 1mm). There is no cartilage, or glands, some smooth muscle is
still present, there are no goblet cells. The epithelium is either columnar or cuboidal.
(AD) means alveolar duct; (BV) blood vessels.

Alveolus (little cavity):
Alveolus is a hollow cavity found in the lung parenchyma, and is the basic unit of
respiration. Lung alveoli are the ends of the respiratory tree, branching from
either alveolar sacs or alveolar ducts (AD), which like alveoli are both sites of gas
exchange with the blood as well. Alveoli are particular to mammalian lungs. Different
structures are involved in gas exchange in other vertebrates. The alveolar membrane
is the gas-exchange surface. Carbon dioxide CO2 rich blood is pumped from the rest
of the body into the alveolar blood vessels where, through diffusion, it releases its
carbon dioxide and absorbs oxygen (O2). The alveoli are located in the respiratory
zone of the lungs, at the ends of the alveolar ducts and alveolar sac, representing the
smallest units in the respiratory tract. The alveoli are tiny air sacs in the lungs where
gas exchange takes place. There are “about 150 million per lung”.  When the
diaphragm contracts, a negative pressure is generated in the thorax and air rushes in
to fill the cavity. When that happens, these sacs fill with air, making the lung expand.
The alveoli are rich with capillaries, called alveolor capillaries (Fig 7b). Here the red
blood cells absorb oxygen from the air and then carry it back in the form of
oxyhaemaglobin, to nourish the cells. The red blood cells also carry carbon dioxide
(CO2) away from the cells in the form of carboxy-hemoglobin and releases it into the
alveoli through the alveolar capillaries. When the diaphragm relaxes, a positive
pressure is generated in the thorax and air rushes out of the alveoli expelling the
carbon dioxide (CO2).
The alveoli consist of an epithelial layer and an extracellular matrix surrounded by
small blood vessels called capillaries. In some alveolar walls there are pores between
alveoli called Pores of Kohn. The alveoli contain some collagen and elastic fibres.
The elastic fibres allow the alveoli to stretch as they are filled with air during
inhalation. They then spring back during exhalation in order to expel the carbon
dioxide-rich air. Alveolar cells, or pneumocytes, are cells lining the alveoli of
the lungs. Two types of alveolar cell exist: type I alveolar cells and type II alveolar
cells.

(Fig. 8 a&b): A 3D and A histologic slide of a human alveolar sac

There are three major types of cell in the alveolar wall–two types of alveolar cell and
a phagocyte.
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 Type-I cells (pneumocyte-I) are thin and flat and form the structure of the
alveoli
 Type-II (pneumocyte-II) cells secrete surfactant to lower the surface tension
of water and allows the membrane to separate, therefore increasing its capability
to exchange gases. Surfactant is continuously released by exocytosis. It forms an
underlying aqueous protein-containing hypophase and an overlying phospholipid
film composed primarily of dipalmitoyl phosphatidylcholine.
 The phagocytes are macrophages, that destroy foreign material, such
as bacteria.
The surfactant is produced by great alveolar cells (granular pneumonocytes,
a cuboidal epithelia), which are the most numerous cells in the alveoli, yet do not
cover as much surface area as the squamous alveolar cells (a squamous
epithelium).

(Fig.9): An alveoli with alveolar cells and surrounding capillaries

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(Fig.10): Schematic diagrams of alveolar wall and cells.

Important notes:
Most of the epithelium (from the nose to the bronchi) is covered in ciliated pseudo-
stratified columnar epithelium, commonly called respiratory epithelium. The cilia beat
in one direction, moving mucus towards the throat where it is swallowed. Moving
down the bronchioles, the cells get more cuboidal in shape but are still ciliated.
Cartilage is present until the small bronchi. In the trachea they are C-shaped rings of 
hyaline cartilage, whereas in the bronchi the cartilage takes the form of interspersed
plates.
Glands are abundant in the upper respiratory tract, but there are fewer lower down and
they are absent starting at the bronchioles. The same goes for goblet cells, although
there are scattered ones in the first bronchioles.
Smooth muscle starts in the trachea, where it joins the C-shaped rings of cartilage. It
continues down the bronchi and bronchioles, which it completely encircles. Instead of
hard cartilage, the bronchi and bronchioles are composed of elastic tissue.
Most of the respiratory tract exists merely as a piping system for air to travel in the
lungs, and alveoli are the only part of the lung that exchanges O2 and CO2 with
the blood.
When a human being inhales, air travels down the trachea, through the bronchial
tubes, and into the lungs. The entire tract is protected by the rib cage, spinal cord, and
sternum bone. In the lungs, oxygen from the inhaled air is transferred into the blood
and circulated throughout the body. CO2 is transferred from returning blood back into
gaseous form in the lungs and exhaled through the lower respiratory tract and then the
upper, to complete the process of breathing. The diaphragm is the primary muscle
that allows for lung expansion and contraction. Smaller muscles between the ribs
(costal muscles) assist with this process.

Defences against infection:

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The human trachea has a membrane lining that produces a layer of mucus that helps
filter waste that an organism breathes in through the air. There is also a small lining of
tiny hairs in our lungs called cilia. These tiny hairs act as a filter in our lungs and
control the amount of mucus that enters our lungs. The reason why we cough is
because the cilia push up the mucus, so not too much enters our lungs. If these
hairs are not functioning properly, an organism is at risk of a lower respiratory tract
infection.
The cilia of the respiratory epithelium beat in concert cranially, effectively moving
secreted mucus containing trapped foreign particles toward the laryngopharynx, for
either expectoration or swallowing to the stomach where the acidic pH helps to
neutralize foreign material and micro-organisms. This system is collectively known as
the mucociliary escalator and serves two functions: to keep the lower respiratory tract
sterile, and to prevent mucus accumulation in the lungs.
The mucocilliary escalator is vital for the movement of mucus up the respiratory tract
to the pharynx. The mucus layer is biphasic with a serous, sol layer in which the cilia
beat and, above this, a viscoelastic or gel layer. Due to the viscous properties of this
upper mucous layer, the tips of the cilia catch in the layer, which may contain
particulate matter, and drag it cranially toward the laryngopharynx.
Upper respiratory tract infections (URI or URTI):
They are illnesses caused by an acute infection which involves the upper respiratory
tract including the nose, sinuses, pharynx or larynx. This commonly includes (1).
Nasal obstruction; (2). Sore throat; (3). Tonsillitis; (4).  Pharyngitis; (5). Laryngitis;
(6). Sinusitis; (7). Otitis media and (8). the common cold. Most infections are viral in
nature and in other instances the cause is bacterial. Upper respiratory tract infections
can also be fungal  or  helminth in origin, but these are rare. 

Lower respiratory tract infections (LRTI):

Our respiratory system is very prone to developing infections in the lungs. Infants and
older adults are more likely to develop infections in their lungs, because their lungs
are not as strong in fighting off these infections. Most of these infections used to be
fatal, but with new research and medicine, they are now treatable. With bacterial
infections, antibiotics are prescribed, while viral infections are harder to treat, but still
curable.
Local defense:
Irritation of nerve endings within the nasal passages or airways, can induce a cough
reflex and sneezing. These responses cause air to be expelled forcefully from the
trachea or nose, respectively. In this manner, irritants caught in the mucus which lines
the respiratory tract are expelled or moved to the mouth where they can
be swallowed. During coughing, contraction of the smooth muscle in the airway walls
narrows the trachea by pulling the ends of the cartilage plates together and by pushing
soft tissue into the lumen. This increases the expired airflow rate to dislodge and
remove any irritant particle or mucus.
Respiratory epithelium can secrete a variety of molecules that aid in the defense of the
lungs which include secretory immunoglobulins (IgA), collectins, defensins and other
peptides. These secretions can act directly as antimicrobials to help keep the airway
free of infection. A variety of chemokines and cytokines are also secreted that recruit
the traditional immune cells and others to site of infections.
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Surfactant immune function is primarily attributed to two proteins: SP-A and SP-D

which can bind to sugars on the surface of pathogens and thereby opsonize them for
uptake by phagocytes. It also regulates inflammatory responses and interacts with the
adaptive immune response. Surfactant degradation or inactivation may contribute to
enhanced susceptibility to lung inflammation and infection.
Most of the respiratory system is lined with mucous membranes that contain mucosa-
associated lymphoid tissue, which produces white blood cells such as lymphocytes.
Some of these infections have environmental factors such as smoking. When you
inhale a tobacco product, the smoke paralyzes the cilia, causing mucus to enter the
lungs. If you smoke frequently, over time these cilia hairs die, and can no longer filter
mucus. Tar from the smoke inhaled enters your lungs, turning the pink-coloured lungs
black. The accumulation of this tar could eventually lead to lung cancer, emphysema
or chronic obstructive pulmonary disease.
1. Lung cancer:
This is a common lower respiratory disease that can be caused by exposure to harmful
chemicals, or prolonged use of tobacco. This disease is chronic and progressive, the
damage to your lungs is irreversible and eventually fatal. This disease destroys the
alveoli, and lung tissue. Damage to these air sacs, and tissue makes breathing very
difficult, causing shortness in breath, hyperventilation, and raised chest. The
decreased amount of alveoli causes loss of oxygen (O2) to the lungs, and more
accumulation of carbon monoxide (CO). There are two types of emphysema: (1).
Primary emphysema can be found in younger adults. This type of emphysema
deteriorates the air sacs, and lung mass. (2). Secondary emphysema can be found in
older adults who smoke/have smoked and have a history of chronic bronchitis.
2. Pneumonia:
The common cold/flu is the most common cause for the upper respiratory tract
infection, which can cause more serious illness that can develop in the lower
respiratory tract. Pneumonia is the most common, and frequent lower respiratory tract
infection. This can be either viral, bacterial, or fungal. This infection is very common,
because pneumonia can be airborne, and when you inhale this infection in the air, the
particles enter the lungs and move into the air sacs. This infection quickly develops in
the lower part of the lung, and fills the lung with fluid, and excess mucus. This causes
difficulty in breathing, and coughing as the lower respiratory tract tries to get rid of
the fluid in the lungs. An individual can be more prone to developing this infection if
you have asthma, flu, heart disease, or cancer.
3. Bronchitis:
It is an inflammation of the bronchial tubes. There are two forms of this infection: (1).
acute bronchitis, which is treatable and can go away without treatment, or (2). chronic
bronchitis, which comes and goes, but will always affect one's lungs. Bronchitis
increases the amount of mucus that is natural in your respiratory tract. Chronic
bronchitis is common in smokers, because the tar from smoking accumulates over
time, causing the lungs to work harder to repair themselves. 
4. Tuberculosis:
Anybody can contract this infection from airborne droplets, and if inhaled you are at
risk of this disease. This is a bacterial infection caused by bacteria Mycobacterium
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tuberculosis (MTB) which deteriorates the lung tissue resulting in coughing up

blood. This infection is deadly if not treated.
5. Asthma:
Our bronchial tubes are the main passages to our right and left lungs. These tubes
carry O2 to the bronchioles inside the lungs. If these tubes swell up, this is the result
of asthma which could lead to an asthma attack. This results in wheezing, tightness of
the chest and severe difficulty in breathing. There are different types of asthma that
affect the functions of the bronchial tubes. Allergies can also set off an allergic
reaction, causing swelling to the bronchial tubes; as a result, the air passage will swell
up, or close up completely. 

Prevention of alveolar collapse

Pulmonary surfactant is a surface-active lipoprotein complex (phospholipoprotein)
formed by type-II alveolar cells. The proteins and lipids that make up the 
surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-
water interface of alveoli, with hydrophilic head groups in the water and the
hydrophobic tails facing towards the air, the main lipid component of surfactant,
dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.

The surface tension of a watery surface tends to make that surface shrink. When that
surface is curved as it is in the alveoli of the lungs, the shrinkage of the surface
decreases the diameter of the alveoli. The more acute the curvature of the water-air
interface the greater the tendency for the alveolus to collapse. This has three effects.
(1). The surface tension inside the alveoli resists expansion of the alveoli during
inhalation. Surfactant reduces the surface tension and therefore makes the lungs
more compliant, or less stiff, than if it were not there; (2). the diameters of the alveoli
increase and decrease during the breathing cycle. This means that the alveoli have
a greater tendency to collapse at the end of exhalation that at the end of inhalation.
Since surfactant floats on the watery surface, its molecules are more tightly packed
together when the alveoli shrink during exhalation. This causes them to have a greater
surface tension-lowering effect when the alveoli are small than when they are large
(as at the end of inhalation, when the surfactant molecules are more widely spaced).
The tendency for the alveoli to collapse is therefore almost the same at the end of
exhalation as at the end of inhalation and (3). The surface tension of the curved
watery layer lining the alveoli tends to draw water from the lung tissues into the
alveoli. Surfactant reduces this danger to negligible levels, and keeps the alveoli dry.
Pre-term babies who are unable to manufacture surfactant have lungs that tend to
collapse each time they breathe out. Unless treated, this condition, called respiratory
distress syndrome, is fatal. Basic scientific experiments, carried out using cells from
chicken lungs, support the potential for using steroids as a means of furthering
development of type II alveolar cells. In fact, once a premature birth is threatened,
every effort is made to delay the birth, and a series of steroid injections is frequently
administered to the mother during this delay in an effort to promote lung maturation.
Functions of each parts of the respiratory system.
larynx  the voice box, where vocal chords are located
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 keeps the windpipe "open"

trachea (windpipe)  trachea is lined with fine hairs called cilia
which filter air before it reaches the lungs

 two branches at the end of the trachea, each

bronchi
lead to a lung

 a network of smaller branches leading from the

bronchioles bronchi into the lung tissue & ultimately to
air sacs

 the functional respiratory units in the lung where

alveoli
gases are exchanged

Malfunctions & Diseases of the Respiratory System

A severe allergic reaction

asthma characterized by the constriction of
bronchioles

Inflammation of the lining of the

 bronchitis
bronchioles

A condition in which the alveoli

emphysema deteriorate, causing the lungs to
lose their elasticity

Caused by the bacteria,

pneumococcus. A condition in
pneumonia which the alveoli become filled
with fluid, preventing the exchange
of gases

An irregular & uncontrolled growth

lung cancer
of tumors in the lung tissue