Basic Sciences-The Human Body - The Respiratory

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First Edition
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The respiratory system / edited by Kara Rogers.

p. cm. -- (The human body)
“In association with Britannica Educational Publishing, Rosen Educational Services.”
Includes bibliographical references and index.
ISBN 978-1-61530-147-8 (library binding)
1. Respiratory organs—Popular works. I. Rogers, Kara.
QP121.R467 2011
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On the cover: The human lungs are extraordinary organs that constantly pump crucial
oxygen through airways and into the bloodstream. © www.istockphoto.com / Sebastian
Kaulitzki
On page 10: Singing is one of many common activities that requires dynamic breath
control. Chip Somodevilla/Getty Images
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CONTENTS
Introduction 10
Chapter 1: Anatomy and

Function of the Human
Respiratory System 19
The Design of the Respiratory
32
System 19
Morphology of the Upper Airways 21
The Nose 21
The Pharynx 24
Morphology of the Lower Airways 25
The Larynx 26
The Trachea and the Stem
Bronchi 28 43
Structural Design of the Airway Tree 29
The Lungs 31
Gross Anatomy 31
Pulmonary Segments 33
The Bronchi and Bronchioles 33
The Gas-Exchange Region 34
Blood Vessels, Lymphatic Vessels,
and Nerves 36
Lung Development 38
Chapter 2: Control and

Mechanics of Breathing 41
Control of Breathing 41
51
Central Organization of Respiratory
Neurons 44
Chemoreceptors 46
Peripheral Chemoreceptors 46
Central Chemoreceptors 48
Muscle and Lung Receptors 49
Variations in Breathing 50
Exercise 51
Sleep 52
The Mechanics of Breathing 53
The Lung–Chest System 55
The Role of Muscles 56
61 The Respiratory Pump and Its
Performance 57
Chapter 3: Gas Exchange and

Respiratory Adaptation 60
Gas Exchange 60
Transport of Oxygen 63
Transport of Carbon Dioxide 65
Gas Exchange in the Lung 68
Abnormal Gas Exchange 69
Interplay of Respiration, Circulation,
and Metabolism 73
Adaptations 78
High Altitudes 79
Swimming and Diving 81
Chapter 4: Infectious Diseases

of the Respiratory System 87
Upper Respiratory System
Infections 88
77 Common Cold 88
Sore Throat 91
Pharyngitis 91
Sinusitis 92
Tonsillitis 94
Lower Respiratory System
Infections 95
Laryngitis 95
Tracheitis 96
Croup 98
Infectious Bronchitis 99
Bronchiolitis 100
Influenza 102
Whooping Cough 105
Psittacosis 107
Pneumonia 108
Legionnaire Disease 113
Tuberculosis 114
115
Chapter 5: Diseases and
Disorders of the
Respiratory System 122
Disorders of the Upper Airway 122
Snoring 123
Sleep Apnea 124
Pickwickian Syndrome 126
Diseases of the Pleura 126
Pleurisy 127
Pleural Effusion and Thoracic
Empyema 127
Pneumothorax 129
Diseases of the Bronchi and
Lungs 130
Bronchiectasis 130
Chronic Bronchitis 131
Pulmonary Emphysema 133
Chronic Obstructive Pulmonary
Disease 136
Lung Congestion 138 123
Atelectasis 141
Lung Infarction 144
Cystic Fibrosis 145
Idiopathic Pulmonary Fibrosis 149
Sarcoidosis and Eosinophilic
Granuloma 149
Pulmonary Alveolar Proteinosis 150
Immunologic Conditions of the
Lung 151
Lung Cancer 152
Diseases of the Mediastinum and
Diaphragm 156
Chapter 6: Allergic and
Occupational Lung Diseases
and Acute Respiratory
Conditions 159
Allergic Lung Diseases 159
Asthma 160
Hay Fever 164
Hypersensitivity Pneumonitis 166
Occupational Lung Disease 167
Silicosis 169
165 Black Lung 170
Asbestosis and Mesothelioma 171
Respiratory Toxicity of Glass and
Metal Fibres 173
Byssinosis 174
Respiratory Toxicity of Industrial
Chemicals 175
Disability and Attribution of
Occupational Lung Diseases 176
Other Respiratory Conditions 177
Circulatory Disorders 177
Respiratory Distress Syndrome 179
Air Pollution 180
167 Carbon Monoxide Poisoning 183
Acidosis 184
Alkalosis and Hyperventilation 184
Hypoxia 186
Altitude Sickness 188
Barotrauma and Decompression
181 Sickness 189
Thoracic Squeeze 192
Drowning 193
Chapter 7: Approaches to
Respiratory Evaluation and
Treatment 196
Recognizing the Signs and Symptoms
of Disease 196
Methods of Investigation 199
Pulmonary Function Test 202
Chest X-ray 203
Lung Ventilation/Perfusion
Scan 204 202
Bronchoscopy 205
Mediastinoscopy 208
Types of Respiratory Therapy 210
Drug Therapies 211
Oxygen Therapy 214
Artificial Respiration 218
Thoracentesis 220
Hyperbaric Chamber 221
Lung Transplantation 223
Conclusion 223
Glossary 226
219
Bibliography 228
Index 230
INTRODUCTION
7 Introduction 7
T he human lungs are amazing feats of nature. They

pump vital oxygen through airways and into the
bloodstream every second of every day. Without this abil-
ity, humans could not survive on Earth.
This book explains the science behind the amazing
human respiratory system. It also sheds light on how eas-
ily a healthy respiratory system can be damaged, whether
by a viral or bacterial infection or through detrimental
habits such as smoking. But there are many treatments to
keep the airways free and clear, and this book also describes
the many different approaches doctors can take to save
patients’ lives and lungs.
The anatomy of the human respiratory system starts
at the place where air first enters the body—the nose. This
structure provides humans with the sense of smell while
also filtering, warming, and moistening inhaled air.
Air that passes through the nose travels to the phar-
ynx, or throat, the cone-shaped passageway leading from
the mouth and nose to the larynx, or voice box. The larynx
is a hollow tube connected to the top of the windpipe, and
this air canal to the lungs not only enables humans to speak
but also keeps food out of the lower respiratory tract.
After passing through the larynx, air travels through
the trachea, also known as the windpipe. Here, the air is
cleansed and moistened before entering the lungs. The
clean air then travels into the deep tissues of the lungs,
eventually reaching the region where gas is exchanged, the
centre of the respiratory system.
The right lung is slightly larger than the left lung
because of the asymmetrical position of the heart. The
right lung has 10 airway segments, and the left lung has 8
to 10. A thin membranous sac known as the pleura covers
the lungs. Inside the lungs, there are numerous nerves and
blood vessels. However, the most prominent feature of
the lung interior are the many small air passages called
11
7 The Respiratory System 7
bronchioles, which range in diameter from 3 mm (0.12

inch) to less than 1 mm (less than 0.04 inch).
The gas-exchange area, the region where oxygen is
transferred to the blood and carbon dioxide is removed,
is made up of three separate compartments for blood, air,
and tissue. The tissue compartment supports the air and
blood compartments and lets them come into close con-
tact, which makes exchanging gases easier, but still keeps
them separate. The exchange of carbon dioxide and oxy-
gen takes place in tiny air sacs called alveoli, which look
like cells in a honeycomb. The average adult lung has
approximately 300 million alveoli.
Lungs also have two distinct blood circulation sys-
tems. The first of these, the pulmonary system, is
characterized by the transport of carbon dioxide–laden
blood from the right side of the heart, through the pulmo-
nary arteries, and to the lungs and by the subsequent
transport of oxygen-rich blood from the lungs, through
the pulmonary veins, and to the left atrium of the heart.
From the heart, the oxygenated blood is pumped to the
rest of the body, thereby delivering oxygen and other
nutrients to organs distant from the lungs. The second
blood system in the lungs, the bronchial circulation, com-
prises the network of blood vessels supporting the
conducting airways themselves. The bronchial circulation
is a vital source of nourishment for the lung tissues.
The act of breathing, or respiration, is an automatic
process, controlled by the brain. Thus, humans and other
animals do not need to actively think about breathing in
order for it to happen. A significant feature of the human
respiratory system is its capacity to instantly adjust to
internal and external stimuli on its own. A series of neural
networks in the brain control the rate of breathing by
communicating with the muscles in the chest and the
12
7 Introduction 7
abdomen. One of the major abdominal muscles involved

in breathing is the diaphragm, which functions to move
air in and out of the lungs as it contracts and relaxes,
respectively.
The neural networks controlling breathing receive
information from special chemical sensors known as che-
moreceptors, which are located throughout the body.
Whereas some chemoreceptors respond to changes in
oxygen and carbon dioxide levels in the bloodstream, oth-
ers respond to chemical changes in the immediate external
environment. Some chemoreceptors send signals to the
brain when they detect noxious or toxic materials in air as
it passes to the lungs. When stimulated, these receptors
constrict the airways and cause breathing to become fast
and shallow. This response represents the body’s attempt
to prevent toxins from entering the lungs. In addition to
the types of sensors described above, there also exist sen-
sors that monitor the muscles that control breathing.
One of the most notable features of respiratory con-
trol is the way in which neural communication between
the body and the brain fine-tunes the rate of breathing in
order to keep carbon dioxide pressure in the blood con-
stant. This fine level of regulation is fundamental in
maintaining the acid–base balance in the body. The effects
of this are illustrated by the differences in respiration rate
observed during exercise and during sleep. During exer-
cise, metabolic rate and acid levels in muscle tissue
increase. These effects trigger an increase in respiration
rate, thereby increasing oxygen delivery to tissues and
maintaining the body’s acid–base balance. In contrast,
during sleep, metabolic rate slows and therefore respira-
tion rate decreases and oxygen demand is low.
In the basic mechanics of breathing, air moves in and
out of the lungs in response to pressure changes. The
13
diaphragm is the major muscle that facilitates breathing,

but it is assisted by a complex assembly of other muscle
groups. The amount of air that the lungs pump changes
dramatically depending on external or internal conditions.
In adults, during vigorous breathing, the volume of air
expired by the lungs can increase by as much as 25 times
the normal resting level.
The lungs serve a fundamental role in ensuring that
excess carbon dioxide is removed from the body. The pul-
monary alveoli, the small air spaces in the lungs, transfer
carbon dioxide from and add oxygen to blood. This
exchange of gases takes place over an immense surface
area. The carbon dioxide that is absorbed by the alveoli is
expelled from the body during exhalation. The oxygen
that the alveoli transfer to the blood is then circulated to
the heart and the body’s other tissues.
Respiration, circulation, and metabolism all work
together. The main purpose of respiration is to provide
oxygen for the body’s cells. Oxygen is used by cells for the
breakdown of nutrients, an activity that is necessary to
supply energy to the cells and the body. Without oxygen,
cells are unable to function properly. Oxygen deprivation,
even for only a few minutes, can cause the brain and the
heart to stop functioning, which can lead to death.
The atmospheric pressure of oxygen differs with
respect to high versus low altitudes on Earth. At high alti-
tudes, oxygen is present at lower levels than it is at low
altitudes. People who live at high altitudes adapt to this
decrease in oxygen availability. However, acclimatization,
in which the body works to more efficiently utilize oxygen
in the air, is a gradual process. Mountain climbers ascend-
ing to extreme heights must spend several days at camps
established increasingly farther up the mountainside, hik-
ing up during the day and descending down to camp to
14
7 Introduction 7
sleep at night. This enables the body to adjust to the

decreased availability of oxygen. If these precautions are
not taken, as climbers make their way up the mountain,
the body’s tissues become deprived of oxygen, which can
lead to high-altitude pulmonary edema, in which the body
circulates additional blood to the lungs, but the blood
leaks into the air sacs. Essentially, death is caused by
drowning.
Various infectious diseases caused by viruses and bac-
teria can produce difficulties in breathing. The common
cold is an acute infection of the upper respiratory tract
that can sometimes spread to the lower respiratory tis-
sues. Other common upper respiratory conditions include
sore throat and pharyngitis, which can arise as a result of
infection. Inflammation of respiratory tissues can some-
times be severe and chronic. For example, many people
have their tonsils removed after suffering from chronic
tonsillitis.
In the lower respiratory system, bacteria can cause
inflammation of the trachea, a condition known as trache-
itis, as well as bacterial pneumonia, which can be
particularly dangerous in infants and in the elderly. Before
antibiotics were widely available, pneumonia was a wide-
spread and notoriously deadly disease. Although bacteria
sometimes cause pneumonia, certain viruses and fungi can
also cause the disease. Pneumonia also often affects per-
sons with impaired immune systems, because these
individuals are unable to defend against infectious
organisms.
Tuberculosis is another example of a respiratory dis-
ease caused by bacteria. In the 18th and 19th centuries, it
was a leading cause of death, and in the first decade of the
21st century, the emergence of drug-resistant tuberculosis
bacteria has resulted in a resurgence of the disease. The
15
tuberculosis bacteria spread slowly in the lungs and cause

hard nodules (tubercles), or large cheese-like masses, to
form. This process leads to the eventual breakdown of
respiratory tissues, resulting in the formation of cavities
in the lungs. Eventually, blood vessels in the lungs burst,
and the infected person coughs up bright red blood.
Influenza is a common, seasonal respiratory illness
that is caused by viral infection. Infection is accompanied
by fever, chills, muscle pains, headaches, and stomach
pain. It is a highly contagious disease too. Every few
decades, a strain of influenza virus gives rise to a pandemic,
an outbreak of the illness that occurs on a global scale and
is characterized by rapid spread. One of the deadliest
influenza pandemics was that of 1918–19, which caused
between 25 million and 50 million deaths worldwide.
Many respiratory conditions arise from noninfectious
causes. For example, snoring is caused by blocked airways,
which may be associated with obesity. A severe form of
snoring is sleep apnea, in which the collapse of the airways
leads to intermittent stoppages in breathing. Sleep apnea
causes affected individuals to awaken periodically through
the night.
Some respiratory diseases are inherited. One of the
best-characterized inherited conditions is cystic fibro-
sis, the primary symptom of which is the production
of a thick, sticky mucus that blocks the airways and
the digestive tract. For some diseases of the respiratory
system, no cause has been identified, despite extensive
research. One example is idiopathic pulmonary fibrosis,
which results in progressive shortness of breath until a
person can no longer breathe. The term idiopathic means
“of unknown cause,” and thus is used to describe diseases
of uncertain origin.
A respiratory disease of major concern in the world
today is lung cancer. Lung cancer can arise as a result of a
16
7 Introduction 7
variety of factors, although tobacco smoking is the pri-

mary cause. Doctors first described the symptoms of lung
cancer in the mid-19th century. In the early 20th century,
it was still considered rare. Now, however, lung cancer is
the leading cause of cancer deaths worldwide, resulting in
an estimated 1.3 million fatalities each year.
Breathing problems caused by allergies to environ-
mental conditions are fairly common. Today, more than 7
percent of children and 9 percent of adults suffer from
asthma, most likely resulting from exposure to air pollu-
tion, tobacco smoke, and even cockroaches.
Some respiratory diseases arise as a result of occupa-
tional, or work, factors. The best-known occupational
lung disease is black lung, which affects coal miners who
inhale coal dust for many years. Construction workers and
insulators exposed to asbestos often suffer from asbesto-
sis, or white lung disease. Breathing asbestos can also
cause the cancerous condition known as mesothelioma.
There is hope for those who suffer from respiratory
diseases and disorders. Scientists are constantly research-
ing and developing new and different treatments for
respiratory ailments. Many treatments, however, have
been around for years and are readily available. Nasal
decongestants and antihistamines are examples of com-
monly used remedies.
Several vaccines have been developed to prevent ill-
nesses such as influenza. Antiviral drugs capable of treating
viral respiratory infections have emerged and become
widely available. The antiviral agents Tamiflu (oseltamivir)
and Relenza (zanamivir) played an important role in treat-
ing persons affected by influenza during the H1N1
influenza pandemic of 2009. In addition to vaccines and
antivirals, antibiotics are vitally important for the treat-
ment of respiratory infections that are caused by bacteria,
particularly pneumonia and tuberculosis.
17
Lung cancer treatments may consist of surgery, che-

motherapy, and radiation. Treatment may also be based on
the results of genetic screening, which can identify muta-
tions that render some lung cancers susceptible to certain
drugs. Sometimes a person’s lung becomes so diseased
that the only hope for survival is a lung transplant.
The best thing a person can do for his or her lungs is to
prevent them from becoming diseased in the first place.
As this book shows, the human respiratory system is a
finely tuned feat of engineering, and the consequences of
neglecting or damaging that fragile system can be drastic.
A healthy set of lungs is nothing to take for granted.
CHAPTER1
ANATOMY AND FUNCTION
OF THE HUMAN
RESPIRATORY SYSTEM
O ur respiratory system provides us with the funda-
mental ability to breathe: to inhale and exhale air
from our lungs. Breathing, or respiration, is fundamental
to survival, and though we possess the ability to consciously
control the rate of our breathing, it is otherwise an auto-
matic process, occurring without our having to think about
it. Yet, as simple as it is for us to inhale and exhale, support-
ing this process are a number of complex actions that occur
within our bodies. These actions encompass not only mus-
cular movements but also cellular and chemical processes.
The respiratory system consists of two divisions: upper
airways and lower airways. The transition between these
two divisions is located where the pathways of the respira-
tory and digestive systems cross, just at the top of the
larynx (or voice box). The upper airway system comprises
the nose and the paranasal cavities (or sinuses), the phar-
ynx (or throat), and part of the oral cavity. The lower
airway system consists of the larynx, the trachea, the stem
bronchi, and all the airways that branch extensively within
the lungs, such as the intrapulmonary bronchi, the bron-
chioles, and the alveolar ducts.
the design of the

respiratory systeM
The human gas–exchanging organ, the lung, is located in
the thorax (or chest), where its delicate tissues are
19
The lungs serve as the gas-exchanging organ for the process of respiration.
Encyclopædia Britannica, Inc.
protected by the bony and muscular thoracic cage. The

lung provides the body with a continuous flow of oxygen
and clears the blood of the gaseous waste product, carbon
dioxide. Atmospheric air is pumped in and out regularly
through a system of pipes, called conducting airways,
20
7 Anatomy and Function of the Human Respiratory System 7
which connect the gas–exchange region inside the body

with the environment outside the body.
For respiration, the collaboration of other organ sys-
tems is essential. The diaphragm, as the main respiratory
muscle, and the intercostal muscles of the chest wall play
an essential role by generating, under the control of the
central nervous system, the pumping action on the lung.
The muscles expand and contract the internal space of the
thorax, whose bony framework is formed by the ribs and
the thoracic vertebrae. Other elements fundamental to the
process of respiration include the blood, which acts as a
carrier of gases, and the circulatory system (i.e., the heart
and the blood vessels), which pumps blood from the heart
to the lungs and the rest of the body.
Morphology of the
upper airways
The nose, sinuses, and pharynx of the upper airways serve
the vital role of filtering and warming air as it enters the
respiratory tract. The filtering process is vital to clearing
inhaled air of dust and other debris, and it protects against
the passage into the lungs of potentially infectious foreign
agents. The oral cavity, through which air may be inhaled
or exhaled, is sometimes also considered a part of the
upper airways. In addition to fulfilling a fundamental role
in respiration, the structures of the upper respiratory tract
also have other important functions, such as enabling the
sensation of smell.
The Nose
The nose is the external protuberance of an internal space,
the nasal cavity. It is subdivided into a left and right canal
by a thin medial cartilaginous and bony wall, the nasal
21
septum. Each canal opens to the face by a nostril and into

the pharynx by the choana. The floor of the nasal cavity is
formed by the palate, which also forms the roof of the oral
cavity. The complex shape of the nasal cavity results from
projections of bony ridges, the superior, middle, and infe-
rior turbinate bones (or conchae), from the lateral wall.
The passageways thus formed below each ridge are called
the superior, middle, and inferior nasal meatuses.
On each side, the intranasal space communicates
with a series of neighbouring air-filled cavities within the
skull (the paranasal sinuses) and also, via the nasolacrimal
duct, with the lacrimal apparatus in the corner of the eye.
The duct drains the lacrimal fluid into the nasal cavity.
This fact explains why nasal respiration can be rapidly
impaired or even impeded during weeping: the lacrimal
fluid is not only overflowing into tears, it is also flooding
the nasal cavity.
The paranasal sinuses are sets of paired single or mul-
tiple cavities of variable size. Most of their development
takes place after birth, and they reach their final size
around age 20. The sinuses are located in four different
skull bones: the maxilla, frontal, ethmoid, and sphenoid
bones. Correspondingly, they are called the maxillary
sinus, which is the largest cavity; the frontal sinus; the eth-
moid sinuses; and the sphenoid sinus, which is located in
the upper posterior wall of the nasal cavity. The sinuses
have two principal functions: because they are filled with
air, they help keep the weight of the skull within reason-
able limits, and they serve as resonance chambers for the
human voice.
The nasal cavity with its adjacent spaces is lined by a
respiratory mucosa. Typically, the mucosa of the nose con-
tains mucus-secreting glands and venous plexuses. Its top
cell layer, the epithelium, consists principally of two cell
types, ciliated and secreting cells. This structural design
22
Sagittal view of the human nasal cavity. Encyclopædia Britannica, Inc.
reflects the particular ancillary functions of the nose and

of the upper airways in general with respect to respira-
tion. They clean, moisten, and warm the inspired air,
preparing it for intimate contact with the delicate tissues
of the gas-exchange area. During expiration through the
nose, the air is dried and cooled, a process that saves water
and energy.
Two regions of the nasal cavity have a different lining.
The vestibule, at the entrance of the nose, is lined by skin
that bears short thick hairs called vibrissae. In the roof of
the nose, the olfactory organ with its sensory epithelium
checks the quality of the inspired air. About two dozen
olfactory nerves convey the sensation of smell from the
23
olfactory cells through the bony roof of the nasal cavity to

the central nervous system.
The Pharynx
For the anatomical description, the pharynx can be
divided into three floors. The upper floor, the nasopharynx,
is primarily a passageway for air and secretions from the
nose to the oral pharynx. It is also connected to the tym-
panic cavity of the middle ear through the auditory tubes
that open on both lateral walls. The act of swallowing
briefly opens the normally collapsed auditory tubes and
allows the middle ears to be aerated and pressure differ-
ences to be equalized. In the posterior wall of the
Sagittal section of the pharynx. Encyclopædia Britannica, Inc.
24
nasopharynx is located a lymphatic organ, the pharyngeal

tonsil. When it is enlarged (as in tonsil hypertrophy), it
may interfere with nasal respiration and alter the reso-
nance pattern of the voice.
The middle floor of the pharynx connects anteriorly to
the mouth and is therefore called the oral pharynx or oro-
pharynx. It is delimited from the nasopharynx by the soft
palate, which roofs the posterior part of the oral cavity.
The lower floor of the pharynx is called the hypophar-
ynx. Its anterior wall is formed by the posterior part of the
tongue. Lying directly above the larynx, it represents the
site where the pathways of air and food cross each other:
air from the nasal cavity flows into the larynx, and food
from the oral cavity is routed to the esophagus directly
behind the larynx. The epiglottis, a cartilaginous, leaf-
shaped flap, functions as a lid to the larynx and, during the
act of swallowing, controls the traffic of air and food.
Morphology of the
lower airways
The major structures of the lower airways include the lar-
ynx, trachea, and lungs. The first two of these provide a
canal for the passage of air to the lungs, while the lungs
themselves receive the air and facilitate the process of gas
exchange. The lungs reside within the thoracic cavity
(chest cavity), which is the second–largest hollow space of
the body. The cavity is enclosed by the ribs, the vertebral
column, and the sternum (or breastbone) and is separated
from the abdominal cavity (the body’s largest hollow
space) by a muscular and membranous partition, the dia-
phragm. Also residing within the thoracic cavity is the
tracheobronchial tree: the heart, the vessels transporting
blood between the heart and the lungs, the great arteries
bringing blood from the heart out into general circulation,
25
and the major veins into which the blood is collected for
transport back to the heart.
The chest cavity is lined with a serous membrane, so
called because it exudes a thin fluid, or serum. This portion
of the chest membrane is called the parietal pleura. The
membrane continues over the lung, where it is called the
visceral pleura, and over part of the esophagus, the heart,
and the great vessels, as the mediastinal pleura, the medi-
astinum being the space and the tissues and structures
between the two lungs. Because the atmospheric pressure
between the parietal pleura and the visceral pleura is less
than that of the outer atmosphere, the two surfaces tend
to touch, friction between the two during the respiratory
movements of the lung being eliminated by the lubricat-
ing actions of the serous fluid. The pleural cavity is the
space, when it occurs, between the parietal and the vis-
ceral pleura.
The Larynx
The larynx is an organ of complex structure that serves a
dual function: as an air canal to the lungs and a controller
of its access, and as the organ of phonation. Sound is pro-
duced by forcing air through a sagittal slit formed by the
vocal cords, the glottis. This causes not only the vocal
cords but also the column of air above them to vibrate. As
evidenced by trained singers, this function can be closely
controlled and finely tuned. Control is achieved by a num-
ber of muscles innervated by the laryngeal nerves. For the
precise function of the muscular apparatus, the muscles
must be anchored to a stabilizing framework.
The laryngeal skeleton consists of almost a dozen
pieces of cartilage, most of them minute, interconnected
by ligaments and membranes. The largest cartilage of the
larynx, the thyroid cartilage, is made of two plates fused
26
anteriorly in the midline. At the upper end of the fusion

line is an incision, the thyroid notch; below it is a forward
projection, the laryngeal prominence. Both of these struc-
tures are easily felt through the skin. The angle between
the two cartilage plates is sharper and the prominence
more marked in men than in women, which has given this
structure the common name of Adam’s apple.
Behind the shieldlike thyroid cartilage, the vocal cords
span the laryngeal lumen. They correspond to elastic liga-
ments attached anteriorly in the angle of the thyroid
shield and posteriorly to a pair of small pyramidal pieces
of cartilage, the arytenoid cartilages. The vocal ligaments
are part of a tube, resembling an organ pipe, made of elas-
tic tissue. Just above the vocal cords, the epiglottis is also
attached to the back of the thyroid plate by its stalk. The
cricoid, another large cartilaginous piece of the laryngeal
skeleton, has a signet-ring shape. The broad plate of the
ring lies in the posterior wall of the larynx and the narrow
arch in the anterior wall. The cricoid is located below the
thyroid cartilage, to which it is joined in an articulation
reinforced by ligaments. The transverse axis of the joint
allows a hingelike rotation between the two cartilages.
This movement tilts the cricoid plate with respect to the
shield of the thyroid cartilage and hence alters the dis-
tance between them. Because the arytenoid cartilages rest
upright on the cricoid plate, they follow its tilting move-
ment. This mechanism plays an important role in altering
length and tension of the vocal cords. The arytenoid carti-
lages articulate with the cricoid plate and hence are able to
rotate and slide to close and open the glottis.
Viewed frontally, the lumen of the laryngeal tube has an
hourglass shape, with its narrowest width at the glottis. Just
above the vocal cords there is an additional pair of mucosal
folds called the false vocal cords or the vestibular folds. Like
the true vocal cords, they are also formed by the free end
27
of a fibroelastic membrane. Between the vestibular folds

and the vocal cords, the laryngeal space enlarges and forms
lateral pockets extending upward. This space is called the
ventricle of the larynx. Because the gap between the ves-
tibular folds is always larger than the gap between the vocal
cords, the latter can easily be seen from above with the
laryngoscope, an instrument designed for visual inspection
of the interior of the larynx.
The muscular apparatus of the larynx comprises two
functionally distinct groups. The intrinsic muscles act
directly or indirectly on the shape, length, and tension of
the vocal cords. The extrinsic muscles act on the larynx as
a whole, moving it upward (e.g., during high-pitched pho-
nation or swallowing) or downward. The intrinsic muscles
attach to the skeletal components of the larynx itself.
The extrinsic muscles join the laryngeal skeleton cranially
to the hyoid bone or to the pharynx and caudally to the
sternum.
The Trachea and the Stem Bronchi

Below the larynx lies the trachea, a tube about 10 to 12 cm
(4 to 5 inches) long and 2 cm (0.8 inch) wide. Its wall is
stiffened by 16 to 20 characteristic horseshoe-shaped,
incomplete cartilage rings that open toward the back and
are embedded in a dense connective tissue. The dorsal
wall contains a strong layer of transverse smooth muscle
fibres that spans the gap of the cartilage. The interior of
the trachea is lined by the typical respiratory epithelium.
The mucosal layer contains mucous glands.
At its lower end, the trachea divides in an inverted
Y into the two stem (or main) bronchi, one each for the
left and right lung. The right main bronchus has a larger
diameter, is oriented more vertically, and is shorter than
the left main bronchus. The practical consequence of
28
this arrangement is that foreign bodies passing beyond

the larynx will usually slip into the right lung. The struc-
ture of the stem bronchi closely matches that of the
trachea.
Structural design of the

airway tree
The hierarchy of the dividing airways, and partly also
of the blood vessels penetrating the lung, largely deter-
mines the internal lung structure. Functionally, the
intrapulmonary airway system can be subdivided into
three zones: a proximal, purely conducting zone; a periph-
eral, purely gas-exchanging zone; and a transitional zone
in between, where both functions grade into one another.
From a morphological point of view, however, it makes
sense to distinguish the relatively thick-walled, purely air-
conducting tubes from those branches of the airway tree
structurally designed to permit gas exchange.
The structural design of the airway tree is functionally
important because the branching pattern plays a role in
determining air flow and particle deposition. In modeling
the human airway tree, it is generally agreed that the air-
ways branch according to the rules of irregular dichotomy.
Regular dichotomy means that each branch of a treelike
structure gives rise to two daughter branches of identical
dimensions. In irregular dichotomy, however, the daugh-
ter branches may differ greatly in length and diameter.
The models calculate the average path from the trachea to
the lung periphery as consisting of about 24 to 25 genera-
tions of branches. Individual paths, however, may range
from 11 to 30 generations. The transition between the
conductive and the respiratory portions of an airway lies
on average at the end of the 16th generation, if the trachea
is counted as generation zero.
29
The conducting airways comprise the trachea, the two

stem bronchi, the bronchi, and the bronchioles. Their
function is to further warm, moisten, and clean the
inspired air and distribute it to the gas-exchanging zone of
the lung. They are lined by the typical respiratory epithe-
lium with ciliated cells and numerous interspersed
mucus-secreting goblet cells. Ciliated cells are present far
down in the airway tree, their height decreasing with the
narrowing of the tubes, as does the frequency of goblet
cells. In bronchioles the goblet cells are completely
replaced by another type of secretory cells named Clara
cells. The epithelium is covered by a layer of low-viscosity
fluid, within which the cilia exert a synchronized, rhyth-
mic beat directed outward. In larger airways, this fluid
layer is topped by a blanket of mucus of high viscosity. The
mucus layer is dragged along by the ciliary action and car-
ries the intercepted particles toward the pharynx, where
they are swallowed. This design can be compared to a con-
veyor belt for particles, and indeed the mechanism is
referred to as the mucociliary escalator.
Whereas cartilage rings or plates provide support for
the walls of the trachea and bronchi, the walls of the bron-
chioles, devoid of cartilage, gain their stability from their
structural integration into the gas-exchanging tissues.
The last purely conductive airway generations in the lung
are the terminal bronchioles. Distally, the airway struc-
ture is greatly altered by the appearance of cuplike
outpouchings from the walls. These form minute air
chambers and represent the first gas-exchanging alveoli
on the airway path. In the alveoli, the respiratory epithe-
lium gives way to a particularly flat lining layer that permits
the formation of a thin air–blood barrier. After several
generations of such respiratory bronchioles, the alveoli
are so densely packed along the airway that an airway wall
30
proper is missing, and the airway consists of alveolar ducts.

The final generations of the airway tree end blindly in the
alveolar sacs.
The lungs
Humans have two lung organs, a right and a left, which are
located in the chest cavity and are responsible for adding
oxygen to and removing carbon dioxide from the blood.
In humans each lung is encased in a thin membranous sac
called the pleura, and each is connected with the trachea
by its main bronchus (large air passageway) and with the
heart by the pulmonary arteries.
Gross Anatomy
Together, the lungs occupy most of the intrathoracic
space. The space between them is filled by the mediasti-
num, which corresponds to a connective tissue space
containing the heart, major blood vessels, the trachea with
the stem bronchi, the esophagus, and the thymus gland.
The right and left lungs are slightly unequal in size. The
right lung represents 56 percent of the total lung volume
and is composed of three lobes, a superior, middle, and
inferior lobe, separated from each other by a deep hori-
zontal and an oblique fissure. The left lung, smaller in
volume because of the asymmetrical position of the heart,
has only two lobes separated by an oblique fissure.
In the thorax, the two lungs rest with their bases on
the diaphragm, while their apexes extend above the first
rib. Medially, they are connected with the mediastinum at
the hilum, a circumscribed area where airways, blood and
lymphatic vessels, and nerves enter or leave the lungs. The
parietal pleura and the visceral pleura that line the inside
31
Anatomy of the human lungs. Encyclopædia Britannica, Inc.
of the thoracic cavities and the lung surface, respectively,

are in direct continuity at the hilum. Depending on the
subjacent structures, the parietal pleura can be subdivided
into three portions: mediastinal, costal, and diaphrag-
matic pleurae. The presence of pleural recesses form a
kind of reserve space, so the pleural cavity is larger than
the lung volume.
During inspiration, the recesses are partly opened by
the expanding lung, thus allowing the lung to increase in
volume. Although the hilum is the only place where the
lungs are secured to surrounding structures, the lungs are
maintained in close apposition to the thoracic wall by a
negative pressure between visceral and parietal pleurae. A
thin film of extracellular fluid between the pleurae enables
32
the lungs to move smoothly along the walls of the cavity

during breathing. If the serous membranes become
inflamed (pleurisy), respiratory movements can be pain-
ful. If air enters a pleural cavity (pneumothorax), the lung
immediately collapses owing to its inherent elastic prop-
erties, and breathing is abolished on this side.
Pulmonary Segments
The lung lobes are subdivided into smaller units, the pul-
monary segments. There are 10 segments in the right lung
and 8 to 10 segments in the left lung, depending on the
classification. Unlike the lobes, the pulmonary segments
are not delimited from each other by fissures but by thin
membranes of connective tissue containing veins and lym-
phatics; the arterial supply follows the segmental bronchi.
These anatomical features are important because patho-
logical processes may be limited to discrete units, and the
surgeon can remove single diseased segments instead of
whole lobes.
The Bronchi and Bronchioles

In the intrapulmonary bronchi, the cartilage rings of the
stem bronchi are replaced by irregular cartilage plates.
Furthermore, a layer of smooth muscle is added between
the mucosa and the fibrocartilaginous tunic. The bronchi
are ensheathed by a layer of loose connective tissue that is
continuous with the other connective tissue elements
of the lung and hence is part of the fibrous skeleton span-
ning the lung from the hilum to the pleural sac. This outer
fibrous layer contains, besides lymphatics and nerves,
small bronchial vessels to supply the bronchial wall with
blood from the systemic circulation. Bronchioles are
33
small conducting airways ranging in diameter from three

to less than one millimetre. The walls of the bronchioles
lack cartilage and seromucous glands. Their lumen is lined
by a simple cuboidal epithelium with ciliated cells and
Clara cells, which produce secretions. The bronchiolar
wall also contains a well-developed layer of smooth mus-
cle cells, capable of narrowing the airway. Abnormal
spasms of this musculature cause the clinical symptoms of
bronchial asthma.
The Gas-Exchange Region

The gas-exchange region comprises three compartments:
air, blood, and tissue. Whereas air and blood are continu-
ously replenished, the function of the tissue compartment
is twofold: it provides the stable supporting framework
for the air and blood compartments, and it allows them to
come into close contact with each other (thereby facilitat-
ing gas exchange) while keeping them strictly confined.
The respiratory gases diffuse from air to blood, and vice
versa, through the 160 square metres (about 1,722 square
feet) of internal surface area of the tissue compartment.
The gas-exchange tissue proper is called the pulmonary
parenchyma, while the supplying structures, conductive
airways, lymphatics, and non-capillary blood vessels
belong to the non-parenchyma.
The gas-exchange region begins with the alveoli
of the first generation of respiratory bronchioles. Distally,
the frequency of alveolar outpocketings increases rapidly,
until after two to four generations of respiratory bron-
chioles, the whole wall is formed by alveoli. The airways
are then called alveolar ducts and, in the last generation,
alveolar sacs. On average, an adult human lung has about
300 million alveoli. They are polyhedral structures, with a
34
diameter of about 250 to 300 micrometres, and open on

one side, where they connect to the airway. The alveolar
wall, called the interalveolar septum, is common to two
adjacent alveoli. It contains a dense network of capillaries,
the smallest of the blood vessels, and a skeleton of con-
nective tissue fibres. The fibre system is interwoven with
the capillaries and particularly reinforced at the alveolar
entrance rings. The capillaries are lined by flat endothelial
cells with thin cytoplasmic extensions.
The interalveolar septum is covered on both sides by
the alveolar epithelial cells. A thin, squamous cell type, the
type I pneumocyte, covers between 92 and 95 percent of
the gas-exchange surface; a second, more cuboidal cell
type, the type II pneumocyte, covers the remaining sur-
face. The type I cells form, together with the endothelial
cells, the thin air–blood barrier for gas exchange, whereas
type II cells are secretory. Type II pneumocytes produce a
surface-tension-reducing material, the pulmonary surfac-
tant, which spreads on the alveolar surface and prevents
the tiny alveolar spaces from collapsing. Before it is
released into the airspaces, pulmonary surfactant is stored
in the type II cells in the form of lamellar bodies. These
granules are the conspicuous ultrastructural features of
this cell type. On top of the epithelium, alveolar macro-
phages creep around within the surfactant fluid. They are
large cells, and their cell bodies abound in granules of vari-
ous content, partly foreign material that may have reached
the alveoli, or cell debris originating from cell damage or
normal cell death. Ultimately, the alveolar macrophages
are derived from the bone marrow, and their task is to
keep the air–blood barrier clean and unobstructed.
The tissue space between the endothelium of the cap-
illaries and the epithelial lining is occupied by the
interstitium. It contains connective tissue and interstitial
35
fluid. The connective tissue comprises a system of fibres,

amorphous ground substance, and cells (mainly fibro-
blasts), which seem to be endowed with contractile
properties. The fibroblasts are thought to control capil-
lary blood flow or, alternatively, to prevent the
accumulation of extracellular fluid in the interalveolar
septa. If for some reason the delicate fluid balance of the
pulmonary tissues is impaired, an excess of fluid accumu-
lates in the lung tissue and within the airspaces. This
pathological condition is called pulmonary edema. As a
consequence, the respiratory gases must diffuse across
longer distances, and proper functioning of the lung is
severely jeopardized.
Blood Vessels, Lymphatic Vessels, and Nerves

With respect to blood circulation, the lung is a complex
organ. It has two distinct but not completely separate vas-
cular systems: a low-pressure pulmonary system and a
high-pressure bronchial system. The pulmonary (or lesser)
circulation is responsible for the oxygen supply of the
organism. Blood, low in oxygen content but laden with
carbon dioxide, is carried from the right heart through the
pulmonary arteries to the lungs. On each side, the pulmo-
nary artery enters the lung in the company of the stem
bronchus and then divides rapidly, following relatively
closely the course of the dividing airway tree. After numer-
ous divisions, small arteries accompany the alveolar ducts
and split up into the alveolar capillary networks. Because
intravascular pressure determines the arterial wall struc-
ture, the pulmonary arteries, which have on average a
pressure five times lower than systemic arteries, are much
flimsier than systemic arteries of corresponding size. The
oxygenated blood from the capillaries is collected by
36
venules and drained into small veins. These do not accom-

pany the airways and arteries but run separately in narrow
strips of connective tissue delimiting small lobules. The
interlobular veins then converge on the intersegmental
septa. Finally, near the hilum the veins merge into large
venous vessels that follow the course of the bronchi.
Generally, four pulmonary veins drain blood from the lung
and deliver it to the left atrium of the heart.
The bronchial circulation has a nutritional function
for the walls of the larger airways and pulmonary vessels.
The bronchial arteries originate from the aorta or from
an intercostal artery. They are small vessels and generally
do not reach as far into the periphery as the conducting
airways. With a few exceptions, they end several genera-
tions short of the terminal bronchioles. They split up into
capillaries surrounding the walls of bronchi and vessels
and also supply adjacent airspaces. Most of their blood is
naturally collected by pulmonary veins. Small bronchial
veins exist, however, originating from the peribronchial
venous plexuses and draining the blood through the
hilum into the azygos and hemiazygos veins of the poste-
rior thoracic wall.
The lymph is drained from the lung through two distinct
but interconnected sets of lymphatic vessels. The superfi-
cial, subpleural lymphatic network collects the lymph from
the peripheral mantle of lung tissue and drains it partly
along the veins toward the hilum. The deep lymphatic sys-
tem originates around the conductive airways and arteries
and converges into vessels that mostly follow the bronchi
and arterial vessels into the mediastinum.
Within the lung and the mediastinum, lymph nodes
exert their filtering action on the lymph before it is
returned into the blood through the major lymphatic ves-
sels, called bronchomediastinal trunks. Lymph drainage
37
paths from the lung are complex. The precise knowledge

of their course is clinically relevant, because malignant
tumours of the lung spread via the lymphatics.
The pleurae, the airways, and the vessels are inner-
vated by afferent and efferent fibres of the autonomic
nervous system. Parasympathetic nerve fibres from the
vagus nerve (10th cranial nerve) and sympathetic branches
of the sympathetic nerve trunk meet around the stem
bronchi to form the pulmonary autonomic nerve plexus,
which penetrates into the lung along the bronchial and
vascular walls. The sympathetic fibres mediate a vasocon-
strictive action in the pulmonary vascular bed and a
secretomotor activity in the bronchial glands. The para-
sympathetic fibres stimulate bronchial constriction.
Afferent fibres to the vagus nerve transmit information
from stretch receptors, and those to the sympathetic
centres carry sensory information (e.g., pain) from the
bronchial mucosa.
Lung Development
After early embryogenesis, during which the lung primor-
dium is laid down, the developing human lung undergoes
four consecutive stages of development, ending after
birth. The names of the stages describe the actual mor-
phology of the prospective airways. The pseudoglandular
stage exists from 5 to 17 weeks; the canalicular stage, from
16 to 26 weeks; the saccular stage, from 24 to 38 weeks; and
finally the alveolar stage, from 36 weeks of fetal age to
about 1 ½ to 2 years after birth.
The lung appears around the 26th day of intrauterine
life as a ventral bud of the prospective esophagus. The bud
separates distally from the gut, divides, and starts to grow
into the surrounding mesenchyme. The epithelial compo-
nents of the lung are thus derived from the gut (i.e., they
38
are of endodermal origin), and the surrounding tissues and

the blood vessels are derivatives of the mesoderm.
Following rapid successive dichotomous divisions, the
lung begins to look like a gland, giving the first stage of
development (pseudoglandular) its name. At the same
time the vascular connections also develop and form a
capillary plexus around the lung tubules. Toward week 17,
all the conducting airways of the lung are preformed, and
it is assumed that, at the outermost periphery, the tips of
the tubules represent the first structures of the prospec-
tive gas-exchange region.
During the canalicular stage, the future lung periphery
develops further. The prospective airspaces enlarge at the
expense of the intervening mesenchyme, and their cuboi-
dal epithelium differentiates into type I and type II
epithelial cells or pneumocytes. Toward the end of this
stage, areas with a thin prospective air–blood barrier have
developed, and surfactant production has started. These
structural and functional developments give a prema-
turely born fetus a small chance to survive at this stage.
During the saccular stage, further generations of
airways are formed. The tremendous expansion of the
prospective respiratory airspaces causes the formation
of saccules and a marked decrease in the interstitial tis-
sue mass. The lung looks more and more “aerated,” but
it is filled with fluid originating from the lungs and from
the amniotic fluid surrounding the fetus. Some weeks
before birth, alveolar formation begins by a septation
process that subdivides the saccules into alveoli. At this
stage of lung development, the infant is born. At birth
the intrapulmonary fluid is rapidly evacuated and the
lung fills with air with the first breaths. Simultaneously,
the pulmonary circulation, which before was practically
bypassed and very little perfused, opens up to accept the
full cardiac output.
39
The newborn lung is far from being a miniaturized

version of the adult lung. It has only about 20 million to
50 million alveoli, or 6 to 15 percent of the full adult com-
plement. Therefore, alveolar formation is completed in
the early postnatal period. Although it was previously
thought that alveolar formation could continue to age
eight and beyond, it is now accepted that the bulk of alve-
olar formation is concluded much earlier, probably before
age two. Even with complete alveolar formation, the lung
is not yet mature. The newly formed interalveolar septa
still contain a double capillary network instead of the
single one of the adult lungs. This means that the pulmo-
nary capillary bed must be completely reorganized during
and after alveolar formation to mature. Only after full
microvascular maturation, which is terminated sometime
between ages two and five, is the lung development com-
pleted, and the lung can enter a phase of normal growth.
40
CHAPTER2
CONTROL AND MECHANICS
OF BREATHING
T he respiratory system is intimately associated with

the brain and central nervous system. Indeed, the
diaphragm and the muscles of the chest are innervated by
neurons that connect to regions of the brain known as the
pons and medulla oblongata. These regions are involved in
the control of autonomic nervous activity and therefore
regulate internal organs without any conscious recognition
or effort. Thus, breathing is an automated function in which
nerve impulses sent from the brain stimulate the respiratory
muscles to contract, thereby producing the mechanical
forces associated with inhalation and exhalation. These
impulses give rise to every breath, and in healthy individu-
als they are sent faithfully for life.
control of breathing
Breathing is an automatic and rhythmic act produced by
networks of neurons in the hindbrain (the pons and
medulla). The neural networks direct muscles that form
the walls of the thorax and abdomen and produce pressure
gradients that move air into and out of the lungs. The
respiratory rhythm and the length of each phase of respi-
ration are set by reciprocal stimulatory and inhibitory
interconnection of these brain-stem neurons.
An important characteristic of the human respiratory
system is its ability to adjust breathing patterns to changes
in both the internal milieu and the external environment.
Ventilation increases and decreases in proportion to
41
swings in carbon dioxide production and oxygen con-

sumption caused by changes in metabolic rate. The
respiratory system is also able to compensate for distur-
bances that affect the mechanics of breathing, such as the
airway narrowing that occurs in an asthmatic attack.
Breathing also undergoes appropriate adjustments when
the mechanical advantage of the respiratory muscles is
altered by postural changes or by movement.
This flexibility in breathing patterns in large part
arises from sensors distributed throughout the body that
send signals to the respiratory neuronal networks in the
brain. Chemoreceptors detect changes in blood oxygen
levels and change the acidity of the blood and brain.
Mechanoreceptors monitor the expansion of the lung, the
size of the airway, the force of respiratory muscle contrac-
tion, and the extent of muscle shortening.
Although the diaphragm is the major muscle of breath-
ing, its respiratory action is assisted and augmented by
a complex assembly of other muscle groups. Intercostal
muscles inserting on the ribs, abdominal muscles, and
muscles such as the scalene and sternocleidomastoid that
attach both to the ribs and to the cervical spine at the base
of the skull also play an important role in the exchange of
air between the atmosphere and the lungs. In addition,
laryngeal muscles and muscles in the oral and nasal phar-
ynx adjust the resistance of movement of gases through
the upper airways during both inspiration and expiration.
Although the use of these different muscle groups adds
considerably to the flexibility of the breathing act, they
also complicate the regulation of breathing. These same
muscles are used to perform a number of other functions,
such as speaking, chewing and swallowing, and maintain-
ing posture.
Perhaps because the “respiratory” muscles are employed
in performing nonrespiratory functions, breathing can be
42
7 Control and Mechanics of Breathing 7
Singing demands a strong diaphragm to control breath. Shutterstock.com
43
influenced by higher brain centres and even controlled vol-

untarily to a substantial degree. An outstanding example
of voluntary control is the ability to suspend breathing
by holding one’s breath. Input into the respiratory con-
trol system from higher brain centres may help optimize
breathing so that not only are metabolic demands satis-
fied by breathing but ventilation also is accomplished with
minimal use of energy.
Central organization of
respiratory neurons
The respiratory rhythm is generated within the pons and
medulla. Three main aggregations of neurons are involved:
a group consisting mainly of inspiratory neurons in the
dorsomedial medulla, a group made up of inspiratory and
expiratory neurons in the ventrolateral medulla, and a
group in the rostral pons consisting mostly of neurons
that discharge in both inspiration and expiration. It is cur-
rently thought that the respiratory cycle of inspiration
and expiration is generated by synaptic interactions within
these groups of neurons.
The inspiratory and expiratory medullary neurons are
connected to projections from higher brain centres and
from chemoreceptors and mechanoreceptors; in turn they
drive cranial motor neurons, which govern the activity of
muscles in the upper airways and the activity of spinal
motor neurons, which supply the diaphragm and other
thoracic and abdominal muscles. The inspiratory and
expiratory medullary neurons also receive input from
nerve cells responsible for cardiovascular and temperature
regulation, allowing the activity of these physiological sys-
tems to be coordinated with respiration.
Neurally, inspiration is characterized by an augment-
ing discharge of medullary neurons that terminates
44
abruptly. After a gap of a few milliseconds, inspiratory

activity is restarted, but at a much lower level, and gradu-
ally declines until the onset of expiratory neuron activity.
Then the cycle begins again. The full development of this
pattern depends on the interaction of several types of
respiratory neurons: inspiratory, early inspiratory, off-
switch, post-inspiratory, and expiratory.
Early inspiratory neurons trigger the augmenting dis-
charge of inspiratory neurons. This increase in activity,
which produces lung expansion, is caused by self-excitation
of the inspiratory neurons and perhaps by the activity of
an as yet undiscovered upstream pattern generator. Off-
switch neurons in the medulla terminate inspiration, but
pontine neurons and input from stretch receptors in the
lung help control the length of inspiration. When the vagus
nerves are sectioned or pontine centres are destroyed,
breathing is characterized by prolonged inspiratory activ-
ity that may last for several minutes. This type of breathing,
which occasionally occurs in persons with diseases of the
brain stem, is called apneustic breathing.
Post-inspiratory neurons are responsible for the declin-
ing discharge of the inspiratory muscles that occurs at the
beginning of expiration. Mechanically, this discharge aids
in slowing expiratory flow rates and probably assists the
efficiency of gas exchange. It is believed by some that these
post-inspiratory neurons have inhibitory effects on both
inspiratory and expiratory neurons and therefore play a
significant role in determining the length of the respira-
tory cycle and the different phases of respiration.
As the activity of the post-inspiratory neurons sub-
sides, expiratory neurons discharge and inspiratory
neurons are strongly inhibited. There may be no periph-
eral manifestation of expiratory neuron discharge except
for the absence of inspiratory muscle activity, although in
upright humans the lower expiratory intercostal muscles
45
and the abdominal muscles may be active even during quiet

breathing. Moreover, as the demand to breathe increases
(for example, with exercise), more expiratory intercostal
and abdominal muscles contract. As expiration proceeds,
the inhibition of the inspiratory muscles gradually dimin-
ishes and inspiratory neurons resume their activity.
Chemoreceptors
One way in which breathing is controlled is through feed-
back by chemoreceptors. There are two kinds of respiratory
chemoreceptors: arterial chemoreceptors, which monitor
and respond to changes in the partial pressure of oxygen and
carbon dioxide in the arterial blood, and central chemore-
ceptors in the brain, which respond to changes in the
partial pressure of carbon dioxide in their immediate envi-
ronment. Ventilation levels behave as if they were regulated
to maintain a constant level of carbon dioxide partial pres-
sure and to ensure adequate oxygen levels in the arterial
blood. Increased activity of chemoreceptors caused by
hypoxia or an increase in the partial pressure of carbon
dioxide augments both the rate and depth of breathing,
which restores partial pressures of oxygen and carbon
dioxide to their usual levels. Conversely, too much ventila-
tion depresses the partial pressure of carbon dioxide,
which leads to a reduction in chemoreceptor activity and
a diminution of ventilation. During sleep and anesthesia,
lowering carbon dioxide levels three to four millimetres of
mercury below values occurring during wakefulness can
cause a total cessation of breathing (apnea).
Peripheral Chemoreceptors
Hypoxia, or the reduction of oxygen supply to tissues to
less than physiological levels (produced, for example, by a
46
trip to high altitudes), stimulates the carotid and aortic

bodies, the principal arterial chemoreceptors. The two
carotid bodies are small organs located in the neck at the
bifurcation of each of the two common carotid arteries
into the internal and external carotid arteries. This organ
is extraordinarily well perfused and responds to changes
in the partial pressure of oxygen in the arterial blood flow-
ing through it rather than to the oxygen content of that
blood (the amount of oxygen chemically combined with
hemoglobin). The sensory nerve from the carotid body
increases its firing rate hyperbolically as the partial pres-
sure of oxygen falls.
In addition to responding to hypoxia, the carotid body
increases its activity linearly as the partial pressure of car-
bon dioxide in arterial blood is raised. This arterial blood
parameter rises and falls as air enters and leaves the lungs,
and the carotid body senses these fluctuations, responding
more to rapid than to slow changes in the partial pressure
of carbon dioxide. Larger oscillations in the partial pres-
sure of carbon dioxide occur with breathing as metabolic
rate is increased. The amplitude of these fluctuations, as
reflected in the size of carotid body signals, may be used by
the brain to detect changes in the metabolic rate and to
produce appropriate adjustment in ventilation.
The carotid body communicates with medullary respi-
ratory neurons through sensory fibres that travel with the
carotid sinus nerve, a branch of the glossopharyngeal
nerve. Microscopically, the carotid body consists of two
different types of cells. The type I cells are arranged in
groups and are surrounded by type II cells. The type II
cells are generally not believed to have a direct role in che-
moreception. Fine sensory nerve fibres are found in
juxtaposition to type I cells, which, unlike type II cells,
contain electron-dense vesicles. Acetylcholine, catechol-
amines, and neuropeptides such as enkephalins, vasoactive
47
intestinal peptide, and substance P, are located within the

vesicles. It is believed that hypoxia and hypercapnia
(excessive carbon dioxide in the blood) cause the release
of one or more of these neuroactive substances from the
type I cells, which then act on the sensory nerve.
It is possible to interfere independently with the
responses of the carotid body to carbon dioxide and oxy-
gen, which suggests that the same mechanisms are not
used to sense or transmit changes in oxygen or carbon
dioxide. The aortic bodies located near the arch of the
aorta also respond to acute changes in the partial pressure
of oxygen, but less well than the carotid body responds to
changes in the partial pressure of carbon dioxide. The aor-
tic bodies are responsible for many of the cardiovascular
effects of hypoxia.
Central Chemoreceptors
Carbon dioxide is one of the most powerful stimulants of
breathing. As the partial pressure of carbon dioxide in
arterial blood rises, ventilation increases nearly linearly.
Ventilation normally increases by two to four litres per
minute with each one millimetre of mercury increase in
the partial pressure of carbon dioxide. Carbon dioxide
increases the acidity of the fluid surrounding the cells but
also easily passes into cells and thus can make the interior
of cells more acidic. It is not clear whether the receptors
respond to the intracellular or extracellular effects of car-
bon dioxide or acidity.
Even if both the carotid and aortic bodies are removed,
inhaling gases that contain carbon dioxide stimulates
breathing. This observation shows that there must be
additional receptors that respond to changes in the partial
pressure of carbon dioxide. Current thinking places these
receptors near the undersurface (ventral part) of the
48
medulla. The same areas of the ventral medulla also con-

tain vasomotor neurons that are concerned with the
regulation of blood pressure. Some investigators argue
that respiratory responses produced at the ventral medul-
lary surface are direct and are caused by interference with
excitatory and inhibitory inputs to respiration from these
vasomotor neurons. They believe that respiratory chemo-
receptors that respond to carbon dioxide are more
diffusely distributed in the brain.
Muscle and Lung Receptors

Receptors in the respiratory muscles and in the lung can
also affect breathing patterns. These receptors are partic-
ularly important when lung function is impaired, because
they can help maintain tidal volume and ventilation at
normal levels.
Changes in the length of a muscle affect the force it
can produce when stimulated. Generally, there is a length
at which the force generated is maximal. Receptors, called
spindles, in the respiratory muscles measure muscle
length and increase motor discharge to the diaphragm
and intercostal muscles when increased stiffness of the
lung or resistance to the movement of air caused by dis-
ease impedes muscle shortening. Tendon organs, another
receptor in muscles, monitor changes in the force pro-
duced by muscle contraction. Too much force stimulates
tendon organs and causes decreasing motor discharge to
the respiratory muscles and may prevent the muscles from
damaging themselves.
Inflation of the lungs in animals stops breathing by a
reflex described by German physiologist Ewald Hering
and Austrian physiologist Josef Breuer. The Hering-Breuer
reflex is initiated by lung expansion, which excites stretch
receptors in the airways. Stimulation of these receptors,
49
which send signals to the medulla by the vagus nerve,

shortens inspiratory times as tidal volume (the volume
of air inspired) increases, accelerating the frequency of
breathing. When lung inflation is prevented, the reflex
allows inspiratory time to be lengthened, helping to pre-
serve tidal volume.
There are also receptors in the airways and in the alve-
oli that are excited by rapid lung inflations and by
chemicals such as histamine, bradykinin, and prostaglan-
dins. The most important function of these receptors,
however, may be to defend the lung against noxious mate-
rial in the atmosphere. When stimulated, these receptors
constrict the airways and cause rapid shallow breathing,
which inhibits the penetration of injurious agents into
the bronchial tree. These receptors are supplied, like the
stretch receptors, by the vagus nerve. Some of these
receptors (called irritant receptors) are innervated by
myelinated nerve fibres, others (the J receptors) by unmy-
elinated fibres. Stimulation of irritant receptors also
causes coughing.
Variations in breathing
Variations in breathing result from changes in metabolic
demands in the tissues of the body. For example, during
exercise, increased levels of oxygen are needed to fuel
muscle function, and thus breathing generally becomes
deeper and the number of breaths taken per minute
increases. At the opposite end of the spectrum, during
sleep, the body’s metabolic rate slows, and thus breathing
typically becomes lighter. However, the association
between sleep and breathing is more complicated than
this because brain activity changes as a person progresses
through the different stages of sleep. This in turn leads to
fluctuations in breathing patterns.
50
Exercise
One of the remarkable features of the respiratory control

system is that ventilation increases sufficiently to keep the
partial pressure of carbon dioxide in arterial blood nearly
unchanged despite the large increases in metabolic rate
that can occur with exercise, thus preserving acid–base
homeostasis. A number of signals arise during exercise
that can augment ventilation. Sources of these signals
include mechanoreceptors in the exercising limbs; the
arterial chemoreceptors, which can sense breath-by-
breath oscillations in the partial pressure of carbon
dioxide; and thermal receptors, because body tempera-
ture rises as metabolism increases.
Mechanoreceptors, arterial chemoreceptors, and thermal receptors all work in

concert during exercise to enhance ventilation. Shutterstock.com
51
The brain also seems to anticipate changes in the met-

abolic rate caused by exercise, because parallel increases
occur in the output from the motor cortex to the exercis-
ing limbs and to respiratory neurons. Changes in the
concentration of potassium and lactic acid in the exercis-
ing muscles acting on unmyelinated nerve fibres may be
another mechanism for stimulation of breathing during
exercise. It remains unclear, however, how these various
mechanisms are adjusted to maintain acid–base balance.
Sleep
During sleep, body metabolism is reduced, but there is an
even greater decline in ventilation so that the partial pres-
sure of carbon dioxide in arterial blood rises slightly and
arterial partial pressure of oxygen falls. The effects on ven-
tilatory pattern vary with sleep stage. In slow-wave sleep,
breathing is diminished but remains regular, whereas in
rapid eye movement sleep, breathing can become quite
erratic. Ventilatory responses to inhaled carbon dioxide
and to hypoxia are less in all sleep stages than during wake-
fulness. Sufficiently large decreases in the partial pressure
of oxygen or increases in the partial pressure of carbon
dioxide will cause arousal and terminate sleep.
During sleep, ventilation may swing between periods
when the amplitude and frequency of breathing are high
and periods in which there is little attempt to breathe, or
even apnea (cessation of breathing). This rhythmic waxing
and waning of breathing, with intermittent periods of
apnea, is called Cheyne-Stokes breathing, after the physi-
cians who first described it. The mechanism that produces
the Cheyne-Stokes ventilation pattern is still argued, but
it may entail unstable feedback regulation of breathing.
Similar swings in ventilation sometimes occur in persons
with heart failure or with central nervous system disease.
52
In addition, ventilation during sleep may intermit-

tently fall to low levels or cease entirely because of partial
or complete blockage of the upper airways. In some indi-
viduals, this intermittent obstruction occurs repeatedly
during the night, leading to severe drops in the levels of
blood oxygenation. The condition, termed sleep apnea
syndrome, occurs most commonly in the elderly, in the
newborn, in males, and in the obese. Because arousal
is often associated with the termination of episodes
of obstruction, sleep is of poor quality, and complaints of
excessive daytime drowsiness are common. Snoring and
disturbed behaviour during sleep may also occur.
In some persons with sleep apnea syndrome, portions
of the larynx and pharynx may be narrowed by fat deposits
or by enlarged tonsils and adenoids, which increase the
likelihood of obstruction. Others, however, have normal
upper airway anatomy, and obstruction may occur because
of discoordinated activity of upper airway and chest wall
muscles. Many of the upper airway muscles, like the
tongue and laryngeal adductors, undergo phasic changes
in their electrical activity synchronous with respiration,
and the reduced activity of these muscles during sleep may
lead to upper airway closure.
The mechanics of breathing

Air moves in and out of the lungs in response to differ-
ences in pressure. When the air pressure within the
alveolar spaces falls below atmospheric pressure, air enters
the lungs (inspiration), provided the larynx is open. When
the air pressure within the alveoli exceeds atmospheric
pressure, air is blown from the lungs (expiration). The flow
of air is rapid or slow in proportion to the magnitude of
the pressure difference. Because atmospheric pressure
remains relatively constant, flow is determined by how
53
The diaphragm contracts and relaxes, forcing air in and out of the lungs.
much above or below atmospheric pressure the pressure

within the lungs rises or falls.
Alveolar pressure fluctuations are caused by expansion
and contraction of the lungs resulting from tensing and
relaxing of the muscles of the chest and abdomen. Each
small increment of expansion transiently increases the
space enclosing lung air. There is, therefore, less air per
unit of volume in the lungs and pressure falls. A difference
in air pressure between atmosphere and lungs is created,
and air flows in until equilibrium with atmospheric pres-
sure is restored at a higher lung volume. When the muscles
of inspiration relax, the volume of chest and lungs
54
decreases, lung air becomes transiently compressed, its

pressure rises above atmospheric pressure, and flow into
the atmosphere results until pressure equilibrium is
reached at the original lung volume. This, then, is the
sequence of events during each normal respiratory cycle:
lung volume change leading to pressure difference, result-
ing in flow of air into or out of the lung and establishment
of a new lung volume.
The Lung–Chest System

The forces that normally cause changes in volume of the
chest and lungs stem not only from muscle contraction
but from the elastic properties of both the lung and the
chest. A lung is similar to a balloon in that it resists
stretch, tending to collapse almost totally unless held
inflated by a pressure difference between its inside and
outside. This tendency of the lung to collapse or pull
away from the chest is measurable by carefully placing a
blunt needle between the outside of the lung and the
inside of the chest wall, thereby allowing the lung to sep-
arate from the chest at this particular spot. The pressure
measured in the small pleural space so created is substan-
tially below atmospheric pressure at a time when the
pressure within the lung itself equals atmospheric pres-
sure. This negative (below-atmospheric) pressure is a
measure, therefore, of the force required to keep the lung
distended. The force increases (pleural pressure becomes
more negative) as the lung is stretched and its volume
increases during inspiration. The force also increases in
proportion to the rapidity with which air is drawn into
the lung and decreases in proportion to the force with
which air is expelled from the lungs. In summary, the
pleural pressure reflects primarily two forces:
55
1. the force required to keep the lung inflated

against its elastic recoil and
2. the force required to cause airflow in and out of
the lung.
Because the pleural pressure is below atmospheric

pressure, air is sucked into the chest and the lung collapses
(pneumothorax) when the chest wall is perforated, as by a
wound or by a surgical incision.
The force required to maintain inflation of the lung
and to cause airflow is provided by the chest and dia-
phragm, which are in turn stretched inward by the pull of
the lungs. The lung– chest system thus acts as two opposed
coiled springs, the length of each of which is affected by
the other. Were it not for the outward traction of the chest
on the lungs, these would collapse. And were it not for the
inward traction of the lungs on the chest and diaphragm,
the chest would expand to a larger size and the diaphragm
would fall from its dome-shaped position within the chest.
The Role of Muscles

The respiratory muscles displace the equilibrium of elas-
tic forces in the lung and chest in one direction or the
other by adding muscular contraction. During inspiration,
muscle contraction is added to the outward elastic force
of the chest to increase the traction on the lung required
for its additional stretch. When these muscles relax, the
additional retraction of lung returns the system to its
equilibrium position.
Contraction of the abdominal muscles displaces the
equilibrium in the opposite direction by adding increased
abdominal pressure to the retraction of lungs, thereby fur-
ther raising the diaphragm and causing forceful expiration.
This additional muscular force is removed on relaxation
56
and the original lung volume is restored. During ordinary

breathing, muscular contraction occurs only on inspira-
tion, expiration being accomplished “passively” by elastic
recoil of the lung.
At total relaxation of the muscles of inspiration and
expiration, the lung is distended to a volume—called the
functional residual capacity—of about 40 percent of its
maximum volume at the end of full inspiration. Further
reduction of the lung volume results from maximal con-
traction of the expiratory muscles of chest and abdomen.
The volume in these circumstances is known as the resid-
ual volume; it is about 20 percent of the volume at the end
of full inspiration (known as the total lung capacity).
Additional collapse of the lung to its “minimal air” can be
accomplished only by opening the chest wall and creating
a pneumothorax.
The membranes of the surface of the lung (visceral
pleura) and on the inside of the chest (parietal pleura) are
normally kept in close proximity (despite the pull of lung
and chest in opposite directions) by surface tension of the
thin layer of fluid covering these surfaces. The strength of
this bond can be appreciated by the attempt to pull apart
two smooth surfaces, such as pieces of glass, separated by
a film of water.
The Respiratory Pump and Its Performance

The energy expended on breathing is used primarily in
stretching the lung– chest system and thus causing airflow.
It normally amounts to 1 percent of the basal energy
requirements of the body but rises substantially during
exercise or illness. The respiratory pump is versatile, capa-
ble of increasing its output 25 times, from a normal resting
level of about six litres (366 cubic inches) per minute to 150
litres (9,154 cubic inches) per minute in adults. Pressures
57
A cough clears the airways with an abrupt opening of the larynx. © www
.istockphoto.com / Jason Lugo
within the lungs can be raised to 130 centimetres of water

(about 1.8 pounds per square inch) by the so-called Valsalva
maneuver—a forceful contraction of the chest and abdom-
inal muscles against a closed glottis (i.e., with no space
between the vocal cords). Airflow velocity, normally reach-
ing 30 litres per minute in quiet breathing, can be raised
voluntarily to 400 litres per minute.
Cough is accomplished by suddenly opening the larynx
during a brief Valsalva maneuver. The resultant high-speed
jet of air is an effective means of clearing the airways of
excessive secretions or foreign particles. The beating
of cilia (hairline projections) from cells lining the airways
58
normally maintains a steady flow of secretions toward the

nose, cough resulting only when this action cannot keep
pace with the rate at which secretions are produced. An
infant takes 33 breaths per minute with a tidal volume (the
amount of air breathed in and out in one cycle) of 15 milli-
litres, totaling about 0.5 litre (approximately one pint) per
minute as compared to adult values of 14 breaths, 500 mil-
lilitres, and seven litres, respectively.
If the force of surface tension is responsible for the
adherence of parietal and visceral pleurae, it is reasonable
to question what keeps the lungs’ alveolar walls (also fluid-
covered) from sticking together and thus eliminating
alveolar airspaces. In fact, such adherence occasionally
does occur and is one of the dreaded complications of pre-
mature births. Normal lungs, however, contain a substance
(a phospholipid surfactant) that reduces surface tension
and keeps alveolar walls separated.
59
CHAPTER3
GAS EXCHANGE AND
RESPIRATORY ADAPTATION
I nhaled air is rich in oxygen, which is needed to support
the functions of the body’s various tissues. For inhaled
oxygen to reach these tissues, however, it must first
undergo a process of gas exchange that occurs at the level
of the alveoli in the lungs. Blood vessels that pass along-
side the alveoli membranes absorb the oxygen and, in
exchange, transfer carbon dioxide to the alveoli. The oxy-
gen is then distributed by the blood to the tissues, whereas
the carbon dioxide is expelled from the alveoli during
exhalation. At high altitudes or during activities such as
deep-sea diving, the respiratory system, as well as other
organ systems, adapt to variations in atmospheric pres-
sure. This process of adaptation is necessary to maintain
normal physiological function.
gas exchange
Respiratory gases—oxygen and carbon dioxide—move
between the air and the blood across the respiratory
exchange surfaces in the lungs. The structure of the human
lung provides an immense internal surface that facilitates
gas exchange between the alveoli and the blood in the pul-
monary capillaries. The area of the alveolar surface in the
adult human is about 160 square metres (1,722 square feet).
Gas exchange across the membranous barrier between
the alveoli and capillaries is enhanced by the thin nature of
the membrane, about 0.5 micrometre, or ¹/¹00 of the
diameter of a human hair.
60
7 Gas Exchange and Respiratory Adaptation 7
Changes in the atmosphere’s pressure occur when deep-sea diving and require
the respiratory system to adapt. Shutterstock.com
61
Respiratory gases move between the environment and

the respiring tissues by two principal mechanisms, con-
vection and diffusion. Convection, or mass flow, is
responsible for movement of air from the environment
into the lungs and for movement of blood between the
lungs and the tissues. Respiratory gases also move by dif-
fusion across tissue barriers such as membranes. Diffusion
is the primary mode of transport of gases between air and
blood in the lungs and between blood and respiring tissues
in the body. The process of diffusion is driven by the dif-
ference in partial pressures of a gas between two locales.
In a mixture of gases, the partial pressure of each gas is
directly proportional to its concentration. The partial
pressure of a gas in fluid is a measure of its tendency to
leave the fluid when exposed to a gas or fluid that does not
contain that gas. A gas will diffuse from an area of greater
partial pressure to an area of lower partial pressure regard-
less of the distribution of the partial pressures of other
gases. There are large changes in the partial pressures of
oxygen and carbon dioxide as these gases move between
air and the respiring tissues. The partial pressure of car-
bon dioxide in this pathway is lower than the partial
pressure of oxygen, caused by differing modes of transport
in the blood, but almost equal quantities of the two gases
are involved in metabolism and gas exchange.
Oxygen and carbon dioxide are transported between
tissue cells and the lungs by the blood. The quantity trans-
ported is determined both by the rapidity with which the
blood circulates and the concentrations of gases in blood.
The rapidity of circulation is determined by the output of
the heart, which in turn is responsive to overall body
requirements. Local flows can be increased selectively, as
occurs, for example, in the flow through skeletal muscles
during exercise. The performance of the heart and circula-
62
tory regulation are, therefore, important determinants of

gas transport.
Oxygen and carbon dioxide are too poorly soluble in
blood to be adequately transported in solution. Specialized
systems for each gas have evolved to increase the quanti-
ties of those gases that can be transported in blood. These
systems are present mainly in the red cells, which make
up 40 to 50 percent of the blood volume in most mam-
mals. Plasma, the cell-free, liquid portion of blood, plays
little role in oxygen exchange but is essential to carbon
dioxide exchange.
Transport of oxygen
Oxygen is poorly soluble in plasma, so less than 2 percent
of oxygen is transported dissolved in plasma. Most oxygen
is bound to hemoglobin, a protein contained within red
cells. Hemoglobin is composed of four iron-containing
ring structures (hemes) chemically bonded to a large pro-
tein (globin). Each iron atom can bind and then release an
oxygen molecule. Enough hemoglobin is present in nor-
mal human blood to permit transport of about 0.2 ml of
oxygen per ml of blood. The quantity of oxygen bound to
hemoglobin is dependent on the partial pressure of oxy-
gen in the lung to which blood is exposed. The curve
representing the content of oxygen in blood at various
partial pressures of oxygen, called the oxygen-dissociation
curve, is a characteristic S-shape because binding of oxy-
gen to one iron atom influences the ability of oxygen to
bind to other iron sites. In alveoli at sea level, the partial
pressure of oxygen is sufficient to bind oxygen to essen-
tially all available iron sites on the hemoglobin molecule.
Not all of the oxygen transported in the blood is
transferred to the tissue cells. The amount of oxygen
63
extracted by the cells depends on their rate of energy

expenditure. At rest, venous blood returning to the lungs
still contains 70 to 75 percent of the oxygen that was pres-
ent in arterial blood. This reserve is available to meet
increased oxygen demands. During extreme exercise the
quantity of oxygen remaining in venous blood decreases
to 10 to 25 percent. At the steepest part of the oxygen-
dissociation curve (the portion between 10 and 40 mm of
mercury partial pressure), a relatively small decline in the
partial pressure of oxygen in the blood is associated with
a relatively large release of bound oxygen.
Hemoglobin binds not only to oxygen but to other
substances as well, including hydrogen ions (which deter-
mine the acidity, or pH, of the blood), carbon dioxide, and
2,3-diphosphoglycerate (2,3-DPG; a salt in the red blood
cells that plays a role in liberating oxygen from hemoglobin
in the peripheral circulation). Although these substances
do not bind to hemoglobin at the oxygen-binding sites,
with the binding of oxygen, changes in the structure of the
hemoglobin molecule occur that affect its ability to bind
other gases or substances. Conversely, binding of these sub-
stances to hemoglobin affects the affinity of hemoglobin
for oxygen. (Affinity denotes the tendency of molecules of
different species to bind to one another.) Increases in hydro-
gen ions, carbon dioxide, or 2,3-DPG decrease the affinity
of hemoglobin for oxygen, and the oxygen-dissociation
curve shifts to the right. Because of this decreased affin-
ity, an increased partial pressure of oxygen is required to
bind a given amount of oxygen to hemoglobin. A rightward
shift of the curve is thought to be of benefit in releasing
oxygen to the tissues when needs are great in relation
to oxygen delivery, as occurs with anemia or extreme
exercise. Reductions in normal concentrations of hydrogen
ions, carbon dioxide, and 2,3-DPG result in an increased
affinity of hemoglobin for oxygen, and the curve is shifted
64
to the left. This displacement increases oxygen binding to

hemoglobin at any given partial pressure of oxygen and
is thought to be beneficial if the availability of oxygen is
reduced, as occurs at extreme altitude.
Temperature changes affect the oxygen-dissociation
curve similarly. An increase in temperature shifts the curve
to the right (decreased affinity; enhanced release of oxy-
gen), whereas a decrease in temperature shifts the curve to
the left (increased affinity). The range of body tempera-
ture usually encountered in humans is relatively narrow, so
that temperature-associated changes in oxygen affinity
have little physiological importance.
Transport of carbon dioxide

Transport of carbon dioxide in the blood is considerably
more complex. A small portion of carbon dioxide, about 5
percent, remains unchanged and is transported dissolved
in blood. The remainder is found in reversible chemical
combinations in red blood cells or plasma. Some carbon
dioxide binds to blood proteins, principally hemoglobin,
to form a compound known as carbamate. About 88 per-
cent of carbon dioxide in the blood is in the form of
bicarbonate ion. The distribution of these chemical spe-
cies between the interior of the red blood cell and the
surrounding plasma varies greatly, with the red blood cells
containing considerably less bicarbonate and more carba-
mate than the plasma.
Less than 10 percent of the total quantity of carbon
dioxide carried in the blood is eliminated during passage
through the lungs. Complete elimination would lead to
large changes in acidity between arterial and venous blood.
Furthermore, blood normally remains in the pulmonary
capillaries less than a second, an insufficient time to elimi-
nate all carbon dioxide.
65
Hemoglobin acts as a natural buffering agent for the acidity that occurs when
carbon dioxide reacts with water. Shutterstock.com
Carbon dioxide enters blood in the tissues because its

local partial pressure is greater than its partial pressure
in blood flowing through the tissues. As carbon dioxide
enters the blood, it combines with water to form carbonic
acid (H2CO3 ), a relatively weak acid, which dissociates into
hydrogen ions (H+) and bicarbonate ions (HCO3-). Blood
acidity is minimally affected by the released hydrogen ions
because blood proteins, especially hemoglobin, are effec-
tive buffering agents. (A buffer solution resists change
in acidity by combining with added hydrogen ions and,
essentially, inactivating them.) The natural conversion of
carbon dioxide to carbonic acid is a relatively slow process.
Carbonic anhydrase, a protein enzyme present inside the
66
red blood cell, catalyzes this reaction with sufficient rapid-

ity that it is accomplished in only a fraction of a second.
Because the enzyme is present only inside the red blood
cell, bicarbonate accumulates to a much greater extent
within the red cell than in the plasma. The capacity of
blood to carry carbon dioxide as bicarbonate is enhanced
by an ion transport system inside the red blood cell mem-
brane that simultaneously moves a bicarbonate ion out
of the cell and into the plasma in exchange for a chloride
ion. The simultaneous exchange of these two ions, known
as the chloride shift, permits the plasma to be used as a
storage site for bicarbonate without changing the electri-
cal charge of either the plasma or the red blood cell. Only
26 percent of the total carbon dioxide content of blood
exists as bicarbonate inside the red blood cell, while 62
percent exists as bicarbonate in plasma. The bulk of bicar-
bonate ions is first produced inside the cell, however, then
transported to the plasma. A reverse sequence of reactions
occurs when blood reaches the lung, where the partial
pressure of carbon dioxide is lower than in the blood.
Hemoglobin acts in another way to facilitate the trans-
port of carbon dioxide. Amino groups of the hemoglobin
molecule react reversibly with carbon dioxide in solution
to yield carbamates. A few amino sites on hemoglobin are
oxylabile, that is, their ability to bind carbon dioxide
depends on the state of oxygenation of the hemoglobin
molecule. The change in molecular configuration of hemo-
globin that accompanies the release of oxygen leads to
increased binding of carbon dioxide to oxylabile amino
groups. Thus, release of oxygen in body tissues enhances
binding of carbon dioxide as carbamate. Oxygenation of
hemoglobin in the lungs has the reverse effect and leads to
carbon dioxide elimination.
Only 5 percent of carbon dioxide in the blood is trans-
ported free in physical solution without chemical change
67
or binding, yet this pool is important, because only

free carbon dioxide easily crosses biologic membranes.
Virtually every molecule of carbon dioxide produced by
metabolism must exist in the free form as it enters blood
in the tissues and leaves capillaries in the lung. Between
these two events, most carbon dioxide is transported as
bicarbonate or carbamate.
Gas exchange in the lung

The introduction of air into the alveoli allows the removal
of carbon dioxide and the addition of oxygen to venous
blood. Because ventilation is a cyclic phenomenon that
occurs through a system of conducting airways, not all
inspired air participates in gas exchange. A portion of the
inspired breath remains in the conducting airways and
does not reach the alveoli where gas exchange occurs. This
portion is approximately one-third of each breath at rest
but decreases to as little as 10 percent during exercise,
because of the increased size of inspired breaths.
In contrast to the cyclic nature of ventilation, blood
flow through the lung is continuous, and almost all
blood entering the lungs participates in gas exchange.
The efficiency of gas exchange is critically dependent on
the uniform distribution of blood flow and inspired air
throughout the lungs. In health, ventilation and blood
flow are extremely well matched in each exchange unit
throughout the lungs. The lower parts of the lung receive
slightly more blood flow than ventilation because grav-
ity has a greater effect on the distribution of blood than
on the distribution of inspired air. Under ideal circum-
stances, partial pressures of oxygen and carbon dioxide
in alveolar gas and arterial blood are identical. Normally
there is a small difference between oxygen tensions in
alveolar gas and arterial blood because of the effect of
68
gravity on matching and the addition of a small amount

of venous drainage to the bloodstream after it has left the
lungs. These events have no measurable effect on carbon
dioxide partial pressures because the difference between
arterial and venous blood is so small.
Abnormal gas exchange

Lung disease can lead to severe abnormalities in blood gas
composition. Because of the differences in oxygen and
carbon dioxide transport, impaired oxygen exchange is far
more common than impaired carbon dioxide exchange.
Mechanisms of abnormal gas exchange are grouped into
four categories: hypoventilation, shunting, ventilation–
blood flow imbalance, and limitations of diffusion.
If the quantity of inspired air entering the lungs is less
than is needed to maintain normal exchange—a condition
known as hypoventilation—the alveolar partial pressure
of carbon dioxide rises and the partial pressure of oxygen
falls almost reciprocally. Similar changes occur in arterial
blood partial pressures because the composition of alveo-
lar gas determines gas partial pressures in blood perfusing
the lungs. This abnormality leads to parallel changes in
both gas and blood and is the only abnormality in gas
exchange that does not cause an increase in the normally
small difference between arterial and alveolar partial pres-
sures of oxygen.
In shunting, venous blood enters the bloodstream
without passing through functioning lung tissue. Shunting
of blood may result from abnormal vascular (blood ves-
sel) communications or from blood flowing through
unventilated portions of the lung (e.g., alveoli filled with
fluid or inflammatory material). A reduction in arterial
blood oxygenation is seen with shunting, but the level of
carbon dioxide in arterial blood is not elevated even
69
though the shunted blood contains more carbon dioxide

than arterial blood.
The differing effects of shunting on oxygen and carbon
dioxide partial pressures are the result of the different
configurations of the blood-dissociation curves of the two
gases. As noted earlier, the oxygen-dissociation curve is
S-shaped and plateaus near the normal alveolar oxygen
partial pressure, but the carbon dioxide–dissociation curve
is steeper and does not plateau as the partial pressure of
carbon dioxide increases. When blood perfusing the col-
lapsed, unventilated area of the lung leaves the lung
without exchanging oxygen or carbon dioxide, the content
of carbon dioxide is greater than the normal carbon diox-
ide content. The remaining healthy portion of the lung
receives both its usual ventilation and the ventilation that
normally would be directed to the abnormal lung. This
lowers the partial pressure of carbon dioxide in the alveoli
of the normal area of the lung. As a result, blood leaving
the healthy portion of the lung has a lower carbon dioxide
content than normal. The lower carbon dioxide content in
this blood counteracts the addition of blood with a higher
carbon dioxide content from the abnormal area, and the
composite arterial blood carbon dioxide content remains
normal. This compensatory mechanism is less efficient
than normal carbon dioxide exchange and requires a mod-
est increase in overall ventilation, which is usually achieved
without difficulty. Because the carbon dioxide–dissocia-
tion curve is steep and relatively linear, compensation for
decreased carbon dioxide exchange in one portion of the
lung can be counterbalanced by increased excretion of car-
bon dioxide in another area of the lung.
In contrast, shunting of venous blood has a substantial
effect on arterial blood oxygen content and partial pres-
sure. Blood leaving an unventilated area of the lung has
70
an oxygen content that is less than the normal content.

In the healthy area of the lung, the increase in ventilation
above normal raises the partial pressure of oxygen in the
alveolar gas and, therefore, in the arterial blood. The oxy-
gen-dissociation curve, however, reaches a plateau at the
normal alveolar partial pressure, and an increase in blood
partial pressure results in a negligible increase in oxygen
content. Mixture of blood from this healthy portion of
the lung (with normal oxygen content) and blood from the
abnormal area of the lung (with decreased oxygen content)
produces a composite arterial oxygen content that is less
than the normal level. Thus, an area of healthy lung can-
not counterbalance the effect of an abnormal portion of
the lung on blood oxygenation because the oxygen-disso-
ciation curve reaches a plateau at a normal alveolar partial
pressure of oxygen. This effect on blood oxygenation is
seen not only in shunting but in any abnormality that
results in a localized reduction in blood oxygen content.
Mismatching of ventilation and blood flow is by far
the most common cause of a decrease in partial pressure
of oxygen in blood. There are minimal changes in blood
carbon dioxide content unless the degree of mismatch is
extremely severe. Inspired air and blood flow normally are
distributed uniformly, and each alveolus receives approxi-
mately equal quantities of both. As matching of inspired
air and blood flow deviates from the normal ratio of 1 to 1,
alveoli become either overventilated or underventilated
in relation to their blood flow. In alveoli that are overven-
tilated, the amount of carbon dioxide eliminated is
increased, which counteracts the fact that there is less
carbon dioxide eliminated in the alveoli that are relatively
underventilated. Overventilated alveoli, however, cannot
compensate in terms of greater oxygenation for under-
ventilated alveoli because, a plateau is reached at the
71
alveolar partial pressure of oxygen, and increased ventila-

tion will not increase blood oxygen content. In healthy
lungs there is a narrow distribution of the ratio of ventila-
tion to blood flow throughout the lung that is centred
around a ratio of 1 to 1. In disease, this distribution can
broaden substantially so that individual alveoli can have
ratios that markedly deviate from the ratio of 1 to 1. Any
deviation from the usual clustering around the ratio of 1 to
1 leads to decreased blood oxygenation: the more dispa-
rate the deviation, the greater the reduction in blood
oxygenation. Carbon dioxide exchange, however, is not
affected by an abnormal ratio of ventilation and blood
flow as long as the increase in ventilation that is required
to maintain carbon dioxide excretion in overventilated
alveoli can be achieved.
A fourth category of abnormal gas exchange involves
limitation of diffusion of gases across the thin membrane
separating the alveoli from the pulmonary capillaries. A
variety of processes can interfere with this orderly
exchange. For oxygen, these include increased thickness
of the alveolar–capillary membrane, loss of surface area
available for diffusion of oxygen, a reduction in the alveo-
lar partial pressure of oxygen required for diffusion, and
decreased time available for exchange due to increased
velocity of flow. These factors are usually grouped under
the broad description of “diffusion limitation,” and any
can cause incomplete transfer of oxygen with a resultant
reduction in blood oxygen content. There is no diffusion
limitation of the exchange of carbon dioxide because this
gas is more soluble than oxygen in the alveolar–capillary
membrane, which facilitates carbon dioxide exchange.
The complex reactions involved in carbon dioxide trans-
port proceed with sufficient rapidity to avoid being a
significant limiting factor in exchange.
72
Interplay of respiration,
circulation, and metabolism
The interplay of respiration, circulation, and metabolism
is the key to the functioning of the respiratory system as
a whole. For gas exchange that takes place in the lungs,
cells set the demand for oxygen uptake and carbon diox-
ide discharge. The circulation of the blood links the
sites of oxygen use and uptake. The proper functioning
of the respiratory system depends on both the ability of
the system to make functional adjustments to varying
needs and the design features of the sequence of struc-
tures involved, which set the limit for respiration.
The main purpose of respiration is to provide oxygen
to the cells at a rate adequate to satisfy their metabolic
needs. This involves transport of oxygen from the lung to
the tissues by means of the circulation of blood. In antiq-
uity and the medieval period, the heart was regarded as a
furnace where the “fire of life” kept the blood boiling.
Modern cell biology has unveiled the truth behind the
metaphor. Each cell maintains a set of furnaces, the mito-
chondria, where, through the oxidation of foodstuffs such
as glucose, the energetic needs of the cells are supplied.
The precise object of respiration therefore is the supply of
oxygen to the mitochondria.
Cell metabolism depends on energy derived from
high-energy phosphates such as adenosine triphosphate
(ATP), whose third phosphate bond can release a quan-
tum of energy to fuel many cell processes, such as the
contraction of muscle fibre proteins or the synthesis of
protein molecules. In the process, ATP is degraded to
adenosine diphosphate (ADP), a molecule with only two
phosphate bonds. To recharge the molecule by adding
the third phosphate group requires energy derived from
73
the breakdown of foodstuffs, or substrates. Two pathways

are available:
1. anaerobic glycolysis, or fermentation, which

operates in the absence of oxygen; and
2. aerobic metabolism, which requires oxygen
and involves the mitochondria.
The anaerobic pathway leads to acid waste products

and is wasteful of resources: the breakdown of one mole-
cule of glucose generates only two molecules of ATP. In
contrast, aerobic metabolism has a higher yield (36 mol-
ecules of ATP per molecule of glucose) and results in
“clean wastes”—water and carbon dioxide, which are eas-
ily eliminated from the body and are recycled by plants in
the process of photosynthesis. For any sustained high-
level cell activity, the aerobic metabolic pathway is
therefore preferable. Because oxidative phosphorylation
occurs only in mitochondria, and since each cell must
produce its own ATP (it cannot be imported), the num-
ber of mitochondria in a cell reflects its capacity for
aerobic metabolism, or its need for oxygen.
The supply of oxygen to the mitochondria at an ade-
quate rate is a critical function of the respiratory system,
because the cells maintain only a limited store of high-
energy phosphates and of oxygen, whereas they usually
have a reasonable supply of substrates in stock. If oxygen
supply is interrupted for a few minutes, many cells, or even
the organism, will die.
Oxygen is collected from environmental air, trans-
ferred to blood in the lungs, and transported by blood
flow to the periphery of the cells where it is discharged to
reach the mitochondria by diffusion. The transfer of
oxygen to the mitochondria involves several structures
and different modes of transports. It begins with
74
ventilation of the lung, which is achieved by convection

or mass flow of air through an ingeniously branched sys-
tem of airways. In the most peripheral airways, ventilation
of alveoli is completed by diffusion of oxygen through
the air to the alveolar surface. The transfer of oxygen
from alveolar air into the capillary blood occurs by diffu-
sion across the tissue barrier. It is driven by the oxygen
partial pressure difference between alveolar air and
capillary blood and depends on the thickness (about
0.5 micrometre) and the surface area of the barrier.
Convective transport by the blood depends on the blood
flow rate (cardiac output) and on the oxygen capacity of
the blood, which is determined by its content of hemo-
globin in the red blood cells. The last step is the diffusive
discharge of oxygen from the capillaries into the tissue
and cells, which is driven by the oxygen partial pressure
difference and depends on the quantity of capillary blood
in the tissue. In this process the blood plays a central role
and affects all transport steps: oxygen uptake in the lung,
transport by blood flow, and discharge to the cells. Blood
also serves as carrier for both respiratory gases: oxygen,
which is bound to hemoglobin in the red blood cells, and
carbon dioxide, which is carried by both plasma and red
blood cells and which also serves as a buffer for acid–base
balance in blood and tissues.
Metabolism, or, more accurately the metabolic rate of
the cells, sets the demand for oxygen. At rest, a human
consumes about 250 ml of oxygen each minute. With
exercise this rate can be increased more than 10-fold in a
normal healthy individual, but a highly trained athlete
may achieve a more than 20-fold increase. As more and
more muscle cells become engaged in doing work, the
demand for ATP and oxygen increases linearly with work
rate. This is accompanied by an increased cardiac output,
essentially resulting from a higher heart rate, and by
75
increased ventilation of the lungs. Consequently, the oxy-

gen partial pressure difference across the air–blood barrier
increases and oxygen transfer by diffusion is augmented.
These dynamic adjustments to the muscles’ needs occur
up to a limit that is twice as high in the athlete as in the
untrained individual. This range of possible oxidative
metabolism from rest to maximal exercise is called the
aerobic scope. The upper limit to oxygen consumption is
not conferred by the ability of muscles to do work, but
rather by the limited ability of the respiratory system to
provide or use oxygen at a higher rate. Muscle can do
more work, but beyond the aerobic scope they must
revert to anaerobic metabolism, with the result that waste
products, mainly lactic acid, accumulate and limit the
duration of work.
The limit to oxidative metabolism is therefore set
by some features of the respiratory system, from the
lung to the mitochondria. Knowing precisely what sets
the limit is important for understanding respiration as
a key vital process, but it is not straightforward, because
of the complexity of the system. Much has been learned
from comparative physiology and morphology, based on
observations that oxygen consumption rates differ signif-
icantly among species. For example, the athletic species
in nature, such as dogs or horses, have an aerobic scope
more than twofold greater than that of other animals of
the same size; this is called adaptive variation. Then, oxy-
gen consumption per unit body mass increases as animals
become smaller, so that a mouse consumes six times as
much oxygen per gram of body mass as a cow, a feature
called allometric variation. Furthermore, the aerobic
scope can be increased by training in an individual, but
this induced variation achieves at best a 50 percent dif-
ference between the untrained and the trained state, well
below interspecies differences.
76
Athletic animals such as dogs have an aerobic scope more than twice that of
similarly sized animals. This difference arises from a phenomenon known as
adaptive variation. Shutterstock.com
Within the aerobic scope the adjustments are caused

by functional variation. For example, cardiac output is
augmented by increasing heart rate. Mounting evidence
indicates that the limit to oxidative metabolism is related
to structural design features of the system. The total
amount of mitochondria in skeletal muscle is strictly pro-
portional to maximal oxygen consumption, in all types of
variation. In training, the mitochondria increase in pro-
portion to the augmented aerobic scope. Mitochondria
set the demand for oxygen, and they seem able to con-
sume up to five millilitres of oxygen per minute and gram
of mitochondria. If energy (ATP) needs to be produced at
a higher rate, the muscle cells make more mitochondria.
77
It is thus possible that oxygen consumption is limited at

the periphery, at the last step of aerobic metabolism. But
it is also possible that more central parts of the respira-
tory system may set the limit to oxygen transport, mainly
the heart, whose capacity to pump blood reaches a limit,
both in terms of rate and of the size of the ventricles,
which determines the volume of blood that can be pumped
with each stroke. The issue of peripheral versus central
limitation is still under debate. It appears, however, that
the lung as a gas-exchanging organ has sufficient redun-
dancy that it does not limit aerobic metabolism at the site
of oxygen uptake. But, whereas the mitochondria, the
blood, the blood vessels, and the heart can increase in
number, rate, or volume to augment their capacity when
energy needs increase, such as in training, the lung lacks
this capacity to adapt. If this proves true, the lung may
well constitute the ultimate limit for the respiratory sys-
tem, beyond which oxidative metabolism cannot be
increased by training.
Adaptations
Adaptation of the respiratory system to different
atmospheric pressures plays a fundamental role in main-
taining the efficiency of gas exchange and gas transport
in the blood. In the case of adaptation to high altitudes,
the structure of the alveoli in the lungs, the levels of
hemoglobin in the blood, and the structure and function
of the energy-producing mitochondria in the cells of tis-
sues may be affected. In the cases of swimming and diving,
physiological changes are more acute in nature and are
influenced by the immediate affects of decreased ventila-
tion or by the affects of increased hydrostatic pressure on
the body.
78
High Altitudes
Ascent from sea level to high altitude has well-known
effects on respiration. The progressive fall in barometric
pressure is accompanied by a fall in the partial pressure of
oxygen, both in the ambient air and in the alveolar spaces
of the lung. This very fall poses the major respiratory chal-
lenge to humans at high altitude. Humans and some other
mammalian species, such as cattle, adjust to the fall in oxy-
gen pressure through the reversible and non-inheritable
process of acclimatization, which, whether undertaken
deliberately or not, commences from the time of exposure
to high altitudes. Indigenous mountain species such as the
At high altitudes, hikers and climbers acclimatize to low oxygen levels by

using oxygen canisters, which heighten the partial pressure of oxygen at all
stages. Barry C. Bishop/National Geographic/Getty Images
79
llama, on the other hand, exhibit an adaptation that is her-

itable and has a genetic basis.
Respiratory acclimatization in humans is achieved
through mechanisms that heighten the partial pressure of
oxygen at all stages, from the alveolar spaces in the lung
to the mitochondria in the cells, where oxygen is needed
for the ultimate biochemical expression of respiration.
The decline in the ambient partial pressure of oxygen is
offset to some extent by greater ventilation, which takes
the form of deeper breathing rather than a faster rate at
rest. Diffusion of oxygen across the alveolar walls into
the blood is facilitated, and in some experimental animal
studies the alveolar walls are thinner at altitude than at sea
level. The scarcity of oxygen at high altitudes stimulates
increased production of hemoglobin and red blood cells,
which increases the amount of oxygen transported to the
tissues. The extra oxygen is released by increased levels of
inorganic phosphates in the red blood cells, such as 2,3-
DPG. With a prolonged stay at altitude, the tissues develop
more blood vessels, and, as capillary density is increased,
the length of the diffusion path along which gases must
pass is decreased—a factor augmenting gas exchange. In
addition, the size of muscle fibres decreases, which also
shortens the diffusion path of oxygen.
The initial response of respiration to the fall of oxy-
gen partial pressure in the blood on ascent to high altitude
occurs in two small nodules, the carotid bodies, attached
to the division of the carotid arteries on either side of the
neck. As the oxygen deprivation persists, the carotid bod-
ies enlarge but become less sensitive to the lack of oxygen.
The low oxygen partial pressure in the lung is associated
with thickening of the small blood vessels in pulmonary
alveolar walls and a slight increase in pulmonary blood
pressure, thought to enhance oxygen perfusion of the
lung apices.
80
Indigenous mountain animals like the llama, alpaca,

and vicuña in the Andes or the yak in the Himalayas are
adapted rather than acclimatized to the low oxygen partial
pressures of high altitude. Their hemoglobin has a high
oxygen affinity, so full saturation of the blood with oxygen
occurs at a lower partial pressure of oxygen. In contrast to
acclimatized humans, these indigenous, adapted moun-
tain species do not have increased levels of hemoglobin or
of organic phosphates in the red cells. They do not develop
small muscular blood vessels or an increased blood pres-
sure in the lung, and their carotid bodies remain small.
Native human highlanders are acclimatized rather
than genetically adapted to the reduced oxygen pressure.
After living many years at high altitude, some highlanders
lose this acclimatization and develop chronic mountain
sickness, sometimes called Monge disease, after the
Peruvian physician who first described it. This disease is
characterized by greater levels of hemoglobin. In Tibet
some infants of Han origin never achieve satisfactory
acclimatization on ascent to high altitude. A chemodec-
toma, or benign tumour, of the carotid bodies may develop
in native highlanders in response to chronic exposure to
low levels of oxygen.
Swimming and Diving

Fluid is not a natural medium for sustaining human life
after the fetal stage. Human respiration requires ventila-
tion with air. Nevertheless, all vertebrates, including
humans, exhibit a set of responses that may be called a
“diving reflex,” which involves cardiovascular and meta-
bolic adaptations to conserve oxygen during diving into
water. Other physiological changes are also observed,
either artificially induced (as by hyperventilation) or
resulting from pressure changes in the environment at the
81
same time that a diver is breathing from an independent

gas supply.
Hyperventilation, a form of overbreathing that
increases the amount of air entering the pulmonary alve-
oli, may be used intentionally by swimmers to prolong
the time they are able to hold their breath underwater.
Hyperventilation can be dangerous, and this danger is
greatly increased if the swimmer descends to depth, as
sometimes happens in snorkeling. The increased ven-
tilation prolongs the duration of the breath-hold by
reducing the carbon dioxide pressure in the blood, but
it cannot provide an equivalent increase in oxygen. Thus
the carbon dioxide that accumulates with exercise takes
longer to reach the threshold at which the swimmer is
forced to take another breath, but the oxygen content of
the blood concurrently falls to unusually low levels. The
increased environmental pressure of the water around
the breath-holding diver increases the partial pressures
of the pulmonary gases. This allows an adequate oxygen
partial pressure to be maintained in the setting of reduced
oxygen content, and consciousness remains unimpaired.
When the accumulated carbon dioxide at last forces the
swimmer to return to the surface, however, the progres-
sively diminishing pressure of the water on his ascent
reduces the partial pressure of the remaining oxygen.
Unconsciousness may then occur in or under the water.
Divers who breathe from an apparatus that delivers
gas at the same pressure as that of the surrounding water
need not return to the surface to breathe and can remain
at depth for prolonged periods. But this apparent advan-
tage introduces additional hazards, many of them unique
in human physiology. Most hazards result from the envi-
ronmental pressure of water. Two factors are involved. At
the depth of a diver, the absolute pressure, which is
82
approximately one additional atmosphere for each

10-metre (33-foot) increment of depth, is one factor. The
other factor, acting at any depth, is the vertical hydrostatic
pressure gradient across the body. The effects of pressure
are seen in many processes at the molecular and cellular
level and include the physiological effects of the increased
partial pressures of the respiratory gases, the increased
density of the respiratory gases, the effect of changes of
pressure upon the volumes of the gas-containing spaces in
the body, and the consequences of the uptake of respira-
tory gases into, and their subsequent elimination from,
the blood and tissues of the diver, often with the forma-
tion of bubbles. The multiple effects of submersion upon
respiration are not easily separated from one another or
clearly distinguishable from related effects of pressure
upon other bodily systems.
The increased work of breathing, rather than cardiac
or muscular performance, is the limiting factor for hard
physical work underwater. Although the increased work of
breathing may largely result from the effects of increased
respiratory gas density upon pulmonary function, the use
of underwater breathing apparatus adds significant exter-
nal breathing resistance to the diver’s respiratory burden.
Arterial carbon dioxide pressure should remain
unchanged during changes of ambient pressure, but the
impaired alveolar ventilation at depth leads to some car-
bon dioxide retention (hypercapnia). This may be
compounded by an increased inspiratory content of car-
bon dioxide, especially if the diver uses closed-circuit and
semiclosed-circuit rebreathing equipment or wears an
inadequately ventilated helmet. Alveolar oxygen levels can
also be disturbed in diving. Hypoxia may result from fail-
ure of the gas supply and may occur without warning.
More commonly, the levels of inspired oxygen are
83
increased. Oxygen in excess can be a poison. At a partial

pressure greater than 1.5 bar (“surface equivalent value” = 150
percent), it may cause the rapid onset of convulsions, and
after prolonged exposures at somewhat lower partial pres-
sures it may cause pulmonary oxygen toxicity with reduced
vital capacity and later pulmonary edema. In mixed-gas
diving, inspired oxygen is therefore maintained at a partial
pressure somewhere between 0.2 and 0.5 bar, but at great
depths the inhomogeneity of alveolar ventilation and the
limitations of gas diffusion appear to require oxygen pro-
vision at greater than normal levels.
The maximum breathing capacity and the maximum
voluntary ventilation of a diver breathing compressed air
diminish rapidly with depth, approximately in proportion
to the reciprocal of the square root of the increasing gas
density. Thus the practice of using an inert gas such as
helium as the oxygen diluent at depths where nitrogen
becomes narcotic, like an anesthetic, has the additional
advantage of providing a breathing gas of lesser density.
The use of hydrogen, which in a mixture with less than 4
percent oxygen is noncombustible, provides a greater
respiratory advantage for deep diving.
At the extreme depths now attainable by humans—
some 500 metres (1,640 feet) in the sea and more than 680
metres (2,230 feet) in the laboratory—direct effects of
pressure upon the respiratory centre may be part of the
“high-pressure neurological syndrome” and may account
for some of the anomalies of breathlessness (dyspnea) and
respiratory control that occur with exercise at depth.
The term carbon dioxide retainer is commonly applied
to a diver who fails to eliminate carbon dioxide in the nor-
mal manner. An ability to tolerate carbon dioxide may
increase the work capacity of a diver at depth but also
may predispose him to other consequences that are less
desirable. High values of end-tidal carbon dioxide with
84
only moderate exertion may be associated with a dimin-

ished tolerance to oxygen neurotoxicity, a condition that,
if it occurs underwater, places the diver at great risk.
Nitrogen narcosis is enhanced by the presence of excess
carbon dioxide, and the physical properties of carbon
dioxide facilitate the nucleation and growth of bubbles on
decompression.
Independent of the depth of the dive are the effects of
the local hydrostatic pressure gradient upon respiration.
The supporting effect of the surrounding water pressure
upon the soft tissues promotes venous return from ves-
sels no longer solely influenced by gravity. And whatever
the orientation of the diver in the water, this approxi-
mates the effects of recumbency upon the cardiovascular
and respiratory systems. Also, the uniform distribution of
gas pressure within the thorax contrasts with the hydro-
static pressure gradient that exists outside the chest.
Intrathoracic pressure may be effectively lower than the
pressure of the surrounding water, in which case more
blood will be shifted into the thorax, or it may be effec-
tively greater, resulting in less intrathoracic blood volume.
The concept of a hydrostatic balance point within the
chest, which represents the net effect of the external
pressures and the effects of chest buoyancy, has proved
useful in designing underwater breathing apparatuses.
Intrapulmonary gas expands exponentially during the
steady return of a diver toward the surface. Unless vented,
the expanding gas may rupture alveolar septa and escape
into interstitial spaces. The extra-alveolar gas may cause a
“burst lung” (pneumothorax) or the tracking of gas into
the tissues of the chest (mediastinal emphysema), possibly
extending into the pericardium or into the neck. More
seriously, the escaped alveolar gas may be carried by the
blood circulation to the brain (arterial gas embolism). This
is a major cause of death among divers. Failure to exhale
85
during ascent causes such accidents and is likely to occur if

the diver makes a rapid emergency ascent, even from
depths as shallow as 2 metres (6.6 feet). Other possible
causes of pulmonary barotrauma include retention of gas
by a diseased portion of lung and gas trapping due to
dynamic airway collapse during forced expiration at low
lung volumes.
Inadequacy of diver decompression, which may
occur as a result of the diver’s failure to follow a correct
decompression protocol or occasionally as a result of a
diver’s idiosyncratic response to an apparently safe
decompression procedure, can result in a sometimes
life-threatening condition known as decompression
sickness. Decompression sickness is caused by the for-
mation of bubbles from gases that were dissolved in the
tissues while the diver was at an increased environmen-
tal pressure.
86
CHAPTER4
INFECTIOUS DISEASES
OF THE RESPIRATORY
SYSTEM
I nfectious diseases are among the most common condi-
tions affecting the human respiratory system. These
diseases may be caused by a variety of agents, including
viruses, bacteria, and molds. Infectious respiratory dis-
eases can be divided into those that affect the upper
respiratory tract and those that affect the lower respira-
tory tract, with this division occurring at the anatomical
level of the larynx. Thus, as considered here, upper respi-
ratory infections include the common cold, pharyngitis,
sinusitis, and tonsillitis, whereas lower respiratory infec-
tions include laryngitis, tracheitis, and any condition of
the bronchi and lungs. However, this distinction is com-
plicated by the fact that diseases of the upper tissues can
spread to the lower tissues.
Examples of severe lower respiratory infections
include croup, various types of pneumonia, Legionnaire
disease, and tuberculosis. Some conditions can cause
extensive lung damage, requiring patient hospitaliza-
tion, and may be highly contagious, resulting in patient
isolation. In most cases, however, infectious diseases,
whether of the upper or lower respiratory tract, can be
effectively treated with prescription antimicrobial
drugs. Other treatments may include the intravenous
administration of fluids and of medications that cannot
be taken orally.
87
Upper respiratory system

infections
The nasal sinuses, pharynx, and tonsils are frequently the
site of both acute and chronic infections. These condi-
tions occur in both children and adults and are readily
spread through exposure to infected individuals. Some of
these infections may resolve on their own, with little or no
medication. In other cases, however, an infection that
spreads to the tissues of the lower respiratory tract may
give rise to debilitating illness that requires extensive
medical intervention.
Common Cold
The common cold is an acute viral infection that starts in
the upper respiratory tract, sometimes spreads to the
lower respiratory structures, and may cause secondary
infections in the eyes or middle ears. More than 200
agents can cause symptoms of the common cold, includ-
ing parainfluenza, influenza, respiratory syncytial viruses,
and reoviruses. Rhinoviruses, however, are the most fre-
quent cause, and some 100 different strains of rhinoviruses
have been associated with coldlike illness in humans.
The popular term common cold reflects the feeling of
chilliness on exposure to a cold environment that is part
of the onset of symptoms. The feeling was originally
believed to have a cause-and-effect relationship with the
disease, but this is now known to be incorrect. The cold is
caught from exposure to infected people, not from a cold
environment, chilled wet feet, or drafts. People can carry
the virus and communicate it without experiencing any
of the symptoms themselves. Incubation is short, usually
one to four days. The viruses start spreading from an
infected person before the symptoms appear, and the
88
7 Infectious Diseases of the Respiratory System 7
spread reaches its peak during the symptomatic phase.

The incidence of colds peaks during the autumn, and
minor epidemics commonly occur throughout the winter,
but the reason for this incidence is unknown. It may result
from the greater amount of time spent indoors, which
increases the likelihood of close contact with those per-
sons carrying cold viruses. Young children can contract
between three and eight colds a year, usually coming into
contact with the infectious agents in day care centres or
preschools.
Cold symptoms vary from person to person, but in the
individual the same symptoms tend to recur in succeed-
ing bouts of infection. Symptoms may include sneezing,
headaches, fatigue, chills, sore throat, inflammation of
the nose (rhinitis), and nasal discharge. There is usually
no fever. The nasal discharge is the first warning that
one has caught a cold. Once a virus becomes established
on the respiratory surface of the nose, its activities irritate
the nose’s cells, which respond by pouring out streams of
clear fluid. This fluid acts to dilute the virus and clear it
from the nose. The sensory organs in the nose are stung
by the inflammatory reaction, thereby setting up sneez-
ing, a second method of expelling the virus. If the virus
penetrates more deeply into the upper respiratory tract,
coughing is added to the infected person’s symptoms in
a further effort to get rid of the virus. Coughing can be
dry or produce amounts of mucus. Symptoms abate as the
host’s defenses increase, the clear fluid often changing
to a thick, yellow-green fluid that is full of the debris of
dead cells. The usual duration of the illness is about five
to seven days, but lingering cough and postnasal discharge
may persist for two weeks or more.
Diagnosis of a cold is usually made by medical history
alone, but it is possible to take a culture for viruses. There
is no effective antiviral agent available for the common
89
Usually, the common cold does not involve a fever, but it can comprise sneez-
ing, headaches, fatigue, chills, sore throat, rhinitis, and nasal discharge.
Shutterstock.com
90
cold. Therapy consists of treating the symptoms: relieving

aches, fever, and nasal congestion. One of the greatest
medical controversies in the past few decades has con-
cerned the efficacy of vitamin C (ascorbic acid) in the
prevention or treatment of the common cold. In many
studies, administration of ascorbic acid has failed to pre-
vent or decrease the symptoms of the common cold.
Sore Throat
Sore throat is a painful inflammation of the passage from
the mouth to the pharynx or of the pharynx itself (pharyn-
gitis). A sore throat may be a symptom of influenza or of
other respiratory infections, a result of irritation by for-
eign objects or fumes, or a reaction to certain drugs.
Infections caused by a strain of streptococcal bacteria and
viruses are often the primary cause of a sore throat.
Generally, the throat reddens, and the tonsils may secrete
pus and become swollen. Microbial agents producing
soreness may remain localized or may spread (by way of
lymph channels or the bloodstream) and produce such
serious complications as rheumatic fever. In treating non-
viral sore throat, antibiotics are often effective, as are
antiseptic gargles. For a viral sore throat, treatment is
aimed at relieving symptoms, which typically subside after
one week.
Pharyngitis
Pharyngitis is an inflammatory illness of the mucous
membranes and underlying structures of the pharynx.
Inflammation usually involves the nasopharynx, uvula,
soft palate, and tonsils. The illness can be caused by
bacteria, viruses, mycoplasmas, fungi, and parasites and
by recognized diseases of uncertain causes. Infection by
91
Streptococcus bacteria may be a complication arising from

a common cold. The symptoms of streptococcal phar-
yngitis (commonly known as strep throat) are generally
redness and swelling of the throat, a pustulant fluid on
the tonsils or discharged from the mouth, extremely sore
throat that is felt during swallowing, swelling of lymph
nodes, and a slight fever; sometimes in children there
are abdominal pain, nausea, headache, and irritability.
Diagnosis is established by a detailed medical history
and by physical examination, and the cause of pharyn-
geal inflammation can be determined by throat culture.
Usually only the symptoms can be treated: throat lozenges
control sore throat and acetaminophen or aspirin control
fever. If a diagnosis of streptococcal infection is estab-
lished by culture, appropriate antibiotic therapy, usually
with penicillin, is instituted. Within approximately three
days the fever leaves, but the other symptoms may persist
for another two to three days.
Viral pharyngitis infections also occur. They can pro-
duce raised whitish to yellow lesions in the pharynx that
are surrounded by reddened tissue. They cause fever, head-
ache, and sore throat that last for 4 to 14 days. Lymphatic
tissue in the pharynx may also become involved. A number
of other infectious diseases may cause pharyngitis, includ-
ing tuberculosis, syphilis, diphtheria, and meningitis.
Sinusitis
Sinusitis is acute or chronic inflammation of the mucosal
lining of one or more paranasal sinuses (the cavities in the
bones that adjoin the nose). Sinusitis commonly accompa-
nies upper respiratory viral infections and in most cases
requires no treatment. Purulent (pus-producing) sinusitis
can occur, however, requiring treatment with antibiotics.
Chronic cases caused by irritants in the environment or by
92
impaired immune systems may require more extended

treatment, including surgery.
The origin of acute sinus infection is much like that
of ear infection. Normally the middle ear and the sinuses
are sterile, but the adjacent mouth and nose have a var-
ied bacterial flora. Under normal conditions, very small
hairs called cilia move mucus along the lining of the nose
and respiratory tract, keeping the sinuses clean. When
ciliary function is damaged, infection can be established.
Following a common cold, a decrease in ciliary function
may permit bacteria to remain on the mucous membrane
surfaces within the sinuses and to produce a purulent
sinusitis. The organisms usually involved are Haemophilus
influenzae, Streptococcus pneumoniae, Staphylococcus aureus,
Streptococcus pyogenes, and many other penicillin-sensitive
anaerobes. Common symptoms include facial pain, head-
ache, and fever following previous upper respiratory viral
illness. On physical examination, persons with sinusitis
are usually found to have an elevation in body tempera-
ture, nasal discharge, and sinus tenderness. Diagnosis
can be confirmed by X-rays of the sinuses and cultures of
material obtained from within the sinuses.
Treatment of acute sinusitis is directed primarily at
overcoming the infecting organism by the use of systemic
antibiotics such as penicillin and at encouraging drainage
of the sinuses by the use of vasoconstricting nose drops
and inhalations. If the infection persists, the pus localized
in any individual sinus may have to be removed by means
of a minor surgical procedure known as lavage, in which
the maxillary or sphenoidal sinuses are irrigated with
water or a saline solution.
Chronic sinusitis may follow repeated or neglected
attacks of acute sinusitis, particularly if impaired breath-
ing or drainage result from nasal polyps or obstructed
sinus openings. It may also be caused by allergy to agents
93
in the environment, such as fungi or pollen. The symp-

toms of chronic sinusitis are a tendency to colds, purulent
nasal discharge, obstructed breathing, loss of smell, and
sometimes headache. Pain is not a feature of chronic
sinusitis. If antibiotic therapy or repeated lavage do not
alleviate the condition, steroidal medications may be
given to relieve swelling and antihistamines to relieve
allergic reactions. In severe cases endoscopic surgery may
be necessary to remove obstructions.
Tonsillitis
Tonsillitis is an inflammatory infection of the tonsils
caused by invasion of the mucous membrane by micro-
organisms, usually hemolytic streptococci or viruses. The
symptoms are sore throat, difficulty in swallowing, fever,
malaise, and enlarged lymph nodes on both sides of the
neck. The infection lasts about five days. The treatment
includes bed rest until the fever has subsided, isolation to
protect others from the infection, and warm throat irriga-
tions or gargles with a mild antiseptic solution. Antibiotics
or sulfonamides or both are prescribed in severe infec-
tions to prevent complications.
The complications of acute streptococcal tonsillitis
are proportional to the severity of the infection. The
infection may extend upward into the nose, sinuses, and
ears or downward into the larynx, trachea, and bronchi.
Locally, virulent bacteria may spread from the infected
tonsil to the adjoining tissues, resulting in a peritonsillar
abscess. More serious are two distant complications—
acute nephritis (kidney inflammation) and acute rheumatic
fever, with or without heart involvement. Repeated acute
infections may cause chronic inflammation of the tonsils,
evidenced by tonsillar enlargement, repeated or persistent
sore throat, and swollen lymph nodes in the neck. The
94
treatment in this case is surgical removal (tonsillectomy).

Scarlet fever, diphtheria, and trench mouth may also pro-
duce acute tonsillitis. In diphtheria the tonsils are covered
with a thick, whitish, adherent membrane; in trench
mouth, with a grayish membrane that wipes off readily.
Lower respiratory system

infections
Infections of the lower respiratory system represent some
of the most frequently occurring life-threatening condi-
tions. For example, pneumonia, which can be caused by
bacterial or viral infection or which may arise secondary to
some other condition, is associated with a high rate of
death in infants and the elderly. Likewise, the infectious
disease tuberculosis, which is a major cause of lung disease
globally, can be exceptionally difficult to treat and may
cause progressive respiratory dysfunction. Thus, infec-
tious diseases of the lower respiratory tissues sometimes
require extensive medical attention, involving long-term
antimicrobial therapy, in order to prevent potentially dis-
abling damage to lung tissue.
Laryngitis
Laryngitis is an inflammation of the larynx that is caused
by chemical or mechanical irritation or by bacterial infec-
tion. Laryngitis is classified as simple, diphtheritic,
tuberculous, or syphilitic. Simple laryngitis is usually asso-
ciated with the common cold or similar infections.
Nonbacterial agents such as chlorine gas, steam, or sulfur
dioxide can also cause severe inflammation. Usually the
mucous membrane lining the larynx is the site of prime
infection. It becomes swollen and filled with blood,
secretes a thick mucous substance, and contains many
95
inflammatory cells. When the epiglottis, which closes the

larynx during swallowing, becomes swollen and infected
by influenza viruses, the larynx can become obstructed,
and suffocation may result. Chronic laryngitis is produced
by excessive smoking, alcoholism, or overuse of the vocal
cords. The mucous membrane becomes dry and covered
with polyps, small lumps of tissue that project from the
surface. The wall of the larynx may thicken and become
inflamed.
Diphtheritic laryngitis is caused by the spread of diph-
theria from the region of the upper throat down to the
larynx. It may cause a membrane of white blood cells, fibrin
(blood clotting protein), and diseased skin cells to attach
to and infiltrate the surface mucous membrane. When
looser portions of this false membrane become dislodged
from part of the larynx, they may consolidate at the vocal
cords and cause an obstruction there. A similar type of
membrane covering can occur in streptococcal infections.
Tuberculous laryngitis is a secondary infection spread
from the initial site in the lungs. Tubercular nodule-like
growths are formed in the larynx tissue. The bacteria die
after infecting the tissue, leaving ulcers on the surface.
There may be eventual destruction of the epiglottis and
laryngeal cartilage.
Syphilitic laryngitis is one of the many complications
of syphilis. In the second stage of syphilis, sores or mucous
patches can form. As the disease advances to the third
stage, tissue destruction is followed by healing and scar for-
mation. The scars can distort the larynx, shorten the vocal
cords, and produce a permanent hoarseness of the voice.
Tracheitis
Tracheitis is an inflammation and infection of the trachea.
Most conditions that affect the trachea are bacterial or
96
viral infections, although irritants like chlorine gas, sulfur

dioxide, and dense smoke can injure the lining of the tra-
chea and increase the likelihood of infections. Acute
infections occur suddenly and usually subside quickly.
Common bacterial causes of acute infections are pneumo-
cocci, streptococci, Neisseria organisms, and staphylococci.
The infections produce fever, fatigue, and swelling of the
mucous membrane lining the trachea. Infections may last
for a week or two and then pass. Generally, they do not
cause significant damage to the tissue unless they become
chronic. Chronic infections recur over a number of years
and cause progressive degeneration of tissue. Irritants
such as heavy smoking and alcoholism may invite infec-
tions. The walls of the trachea during chronic infection
contain an excess of white blood cells. Blood vessels
increase in number, and the walls thicken because of an
increase in elastic and muscle fibres. The mucous glands
may become swollen, and small polyplike formations
occasionally grow. Degenerated tissue is eventually
replaced by a fibrous scar tissue.
Diphtheria, smallpox, tuberculosis, and syphilis all
afflict the trachea. Diphtheria usually involves the upper
mouth and throat, but the trachea may also be attacked. A
false membrane composed of white blood cells and fibrin
(clotting protein) coat the surface of the trachea. Typhoid
causes swelling and ulceration in the lymph tissue. It can
occasionally ulcerate the cartilage of the trachea and
destroy tissue. In smallpox, pustules and ulcers, such as
those that occur on the external skin, form in the mucous
membrane. Intense blood congestion, hemorrhages, and
degeneration of the tracheal tissue can occur. Tuberculosis
causes nodules and ulcers that start on the membrane and
progress through the tissue to the cartilage. The cartilage
deteriorates and sometimes breaks apart causing severe
pain and swelling. Syphilis forms lesions that erode the
97
tissue, and can cause thickening and stiffening of the

spaces between the cartilage.
Croup
Croup is an acute respiratory illness of young children that
is characterized by a harsh cough, hoarseness, and difficult
breathing. It is most often caused by an infection of the
airway in the region of the larynx and trachea. Some cases
result from allergy or physical irritation of these tissues.
The symptoms are caused by inflammation of the laryn-
geal membranes, spasms of the laryngeal muscles, or
inflammation around the trachea. In some cases, inflam-
mation occurs around the bronchial tree.
Viral infections are the most common cause of croup,
the most frequent being those with the parainfluenza and
influenza viruses. Such infections are most prevalent
among children younger than age three, and they strike
most frequently in late fall and winter. Generally, the onset
of viral croup is preceded by the symptoms of the com-
mon cold for several days. Most children with viral croup
can be treated at home with the inhalation of mist from an
appropriate vaporizer. Epinephrine and corticosteroids
have also been used to reduce swelling of the airway. In
cases of severe airway obstruction, hospitalization may be
necessary.
Bacterial croup, also called epiglottitis, is a more seri-
ous condition that is often caused by Haemophilus
influenzae type B. It is characterized by marked swelling
of the epiglottis, a flap of tissue that covers the air pas-
sage to the lungs and that channels food to the esophagus.
The onset is usually abrupt, with high fever and breathing
difficulties. Because of the marked swelling of the epi-
glottis, there is obstruction at the opening of the trachea,
making it necessary for the patient to sit and lean
98
forward to maximize the airflow. Epiglottitis generally

strikes children between ages three and seven. Children
with epiglottitis require prompt medical attention. An
artificial airway must be opened, preferably by inserting a
tube down the windpipe. Patients are given antibiotics,
which generally relieve the inflammation within 24 to 72
hours. The occurrence of epiglottitis has decreased in
the Western world owing to an effective vaccine against
H. influenzae.
Infectious Bronchitis
Infectious bronchitis is an inflammation of all or part of
the bronchial tree (the bronchi), through which air passes
into the lungs. The most obvious symptoms are a sensa-
tion of chest congestion and a mucus-producing cough.
Under ordinary circumstances, the sensitive mucous
membranes lining the inner surfaces of the bronchi are
well protected from inhaled infectious organisms by the
filtering function of the nose and throat and by the cough
reflex. Under certain circumstances, however, organisms
do enter the airways and initiate a sudden and rapid
attack, resulting usually in a relatively brief disease called
acute infectious bronchitis. Acute infectious bronchitis
is an episode of recurrent coughing and mucus produc-
tion lasting several days to several weeks. It is most
frequently caused by viruses responsible for upper respi-
ratory infections. Therefore, it is often part of the
common cold and is a common sequel to influenza,
whooping cough, and measles. Acute bronchitis can also
be caused by bacteria such as Streptococcus, particularly in
people who have underlying chronic lung disease. In addi-
tion, it is sometimes precipitated by chemical irritants
such as toxic gases or the fumes of strong acids, ammonia,
or organic solvents.
99
Treatment of acute bronchitis is largely symptomatic

and of limited benefit. Steam inhalation, bronchodila-
tors, and expectorants will usually relieve the symptoms.
Bacterial acute bronchitis responds to treatment with
an appropriate antibiotic. Another form of bronchitis,
discussed in a later chapter, is a long-standing, repetitive
condition, called chronic bronchitis, which results in
protracted and often permanent damage to the bron-
chial mucosa.
Bronchiolitis
Bronchiolitis refers to inflammation of the small airways.
Bronchiolitis probably occurs to some extent in acute
viral disorders, particularly in children between ages one
and two, and particularly in infections with respiratory
syncytial virus. In some cases the inflammation may be
severe enough to threaten life, but it normally clears spon-
taneously, with complete healing in all but a very small
percentage of cases. In adults, acute bronchiolitis of this
kind is not a well-recognized clinical syndrome, though
there is little doubt that in most patients with chronic
bronchitis, acute exacerbations of infection are associated
with further damage to small airways. In isolated cases, an
acute bronchiolitis episode is followed by a chronic oblit-
erative condition, or this may develop slowly over time.
This pattern of occurrence has only recently been recog-
nized. In addition to patients acutely exposed to gases, in
whom such a syndrome may follow the acute exposure,
patients with rheumatoid arthritis may develop a slowly
progressive obliterative bronchiolitis that may prove fatal.
An obliterative bronchiolitis may appear after bone mar-
row replacement for leukemia and may cause shortness of
breath and disability.
100
Welding in enclosed spaces often results in exposure to oxides of nitrogen, but a

short cough and progressive shortness of breath may not be evident for hours.
Monty Rakusen/Cultura/Getty Images
Exposure to oxides of nitrogen, which may occur from

inhaling gas in silos, when welding in enclosed spaces such
as boilers, after blasting underground, or in fires involv-
ing plastic materials, is characteristically not followed
by acute symptoms. These develop some hours later,
when the victim develops a short cough and progressive
shortness of breath. A chest radiograph shows patchy
inflammatory change, and the lesion is an acute bron-
chiolitis. Symptomatic recovery may mask incomplete
resolution of the inflammation.
An inflammation around the small airways, known as a
respiratory bronchiolitis, is believed to be the earliest
change that occurs in the lung in cigarette smokers,
101
although it does not lead to symptoms of disease at that

stage. The inflammation is probably reversible if smoking
is discontinued. It is not known whether those who
develop this change (after possibly only a few years of
smoking) are or are not at special risk of developing the
long-term changes of chronic bronchitis and emphysema.
Influenza
Influenza, also known simply as the flu (or grippe), is an
acute viral infection of the upper or lower respiratory
tract that is marked by fever, chills, and a generalized feel-
ing of weakness and pain in the muscles, together with
varying degrees of soreness in the head and abdomen.
The flu may affect individuals of all ages, though the high-
est incidence of the disease is among children and young
adults, and it is generally more frequent during the colder
months of the year.
Transmission and Symptoms

Influenza viruses are transmitted from person to person
through the respiratory tract, by such means as inhalation
of infected droplets resulting from coughing and sneez-
ing. As the virus particles gain entrance to the body, they
selectively attack and destroy the ciliated epithelial cells
that line the upper respiratory tract, bronchial tubes, and
trachea. The incubation period of the disease is one to
two days, after which the onset of symptoms is abrupt,
with sudden and distinct chills, fatigue, and muscle aches.
The temperature rises rapidly to 38–40 °C (101–104 °F). A
diffuse headache and severe muscular aches throughout
the body are experienced, often accompanied by irritation
or a sense of rawness in the throat. In three to four days
the temperature begins to fall, and the person begins to
recover. Symptoms associated with respiratory tract
102
infection, such as coughing and nasal discharge, become

more prominent and may be accompanied by lingering
feelings of weakness. Death may occur, usually among
older people already weakened by other debilitating disor-
ders, and is caused in most of those cases by complications
such as pneumonia or bronchitis.
Treatment and Prevention

The antiviral drugs amantadine and rimantadine have
beneficial effects on cases of influenza involving a strain of
virus known as influenza type A. However, viral resistance
to these agents has been observed, thereby reducing their
effectiveness. A newer category of drugs, the neuramini-
dase inhibitors, which includes oseltamivir (Tamiflu) and
zanamivir (Relenza), was introduced in the late 1990s;
these drugs inhibit influenza A, as well as a strain of virus
known as influenza type B. Other than this, the standard
treatment remains bed rest, ingestion of fluids, and the
use of analgesics to control fever. It is recommended that
children and teenagers with the flu not be given aspirin, as
treatment of viral infections with aspirin is associated
with Reye syndrome, a very serious illness.
Individual protection against the flu may be bolstered
by injection of a vaccine containing two or more circulat-
ing influenza viruses. These viruses are produced in chick
embryos and rendered noninfective; standard commercial
preparations ordinarily include the type B influenza virus
and several of the A subtypes. Protection from one vacci-
nation seldom lasts more than a year, and yearly vaccination
may be recommended, particularly for those individuals
who are unusually susceptible to influenza or whose weak
condition could lead to serious complications in case of
infection. However, routine immunization in healthy
people is also recommended. In order to prevent human-
infecting bird flu viruses from mutating into more
103
dangerous subtypes, public health authorities try to limit

the viral “reservoir” where antigenic shift may take place
by ordering the destruction of infected poultry flocks.
Oseltamivir (Tamiflu)
Oseltamivir is an antiviral drug that is active against both
influenza type A and influenza type B viruses. Oseltamivir
and a similar agent called zanamivir (marketed as Relenza)
were approved in 1999 by the U.S. Food and Drug
Administration and represented the first members in a
new class of antiviral drugs known as neuraminidase
inhibitors. Oseltamivir is marketed as Tamiflu by the U.S.-
based pharmaceutical company Hoffman–La Roche, Inc.
Oseltamivir can be given orally. Through the inhibi-
tion of neuraminidase, a glycoprotein on the surface of
influenza viruses, the drug decreases the release of virus
from infected cells, increases the formation of viral aggre-
gates, and decreases the spread of the virus through the
body. Oseltamivir is effective when administered within
two days of symptom onset. The drug can also be used to
prevent flu in adults and children who take the medication
once daily for a period of at least 10 days. There is evidence
that the most common subtype of influenza type A virus,
known as H1N1, has developed resistance to oseltamivir.
Zanamivir (Relenza)
Zanamivir is an antiviral drug that is active against both
influenza type A and influenza type B viruses. It is sold
under the trade name Relenza by the pharmaceutical
company GlaxoSmithKline. Zanamivir is given by inhala-
tion only. By inhibiting the neuraminidase glycoprotein
on the surface of the influenza virus, zanamivir decreases
the release of virus from infected cells, increases the for-
mation of viral aggregates, and decreases the spread of the
virus through the body. If taken within 30 hours of
104
the onset of influenza, zanamivir can shorten the dura-

tion of the illness. Zanamivir, when taken once daily for
10 to 28 days, can prevent influenza infection in some
adults and children.
Whooping Cough
Whooping cough, or pertussis, is an acute, highly com-
municable respiratory disease. It is characterized in its
typical form by paroxysms of coughing followed by a
long-drawn inspiration, or “whoop.” The coughing ends
with the expulsion of clear, sticky mucus and often with
vomiting. Whooping cough is caused by the bacterium
Bordatella pertussis.
Bordetella pertussis, the causative agent of whooping cough, isolated and

coloured with Gram stain. Centers for Disease Control and Prevention
(CDC) (Image Number: 2121)
105
Whooping cough is passed from one person directly

to another by inhalation of droplets expelled by cough-
ing or sneezing. Beginning its onset after an incubation
period of approximately one week, the illness progresses
through three stages—catarrhal, paroxysmal, and conva-
lescent—which together last six to eight weeks. Catarrhal
symptoms are those of a cold, with a short dry cough that
is worse at night, red eyes, and a low-grade fever. After one
to two weeks the catarrhal stage passes into the distinctive
paroxysmal period, variable in duration but commonly
lasting four to six weeks. In the paroxysmal state, there is
a repetitive series of coughs that are exhausting and often
result in vomiting. The infected person may appear blue,
with bulging eyes, and be dazed and apathetic, but the
periods between coughing paroxysms are comfortable.
During the convalescent stage there is gradual recovery.
Complications of whooping cough include pneumonia,
ear infections, slowed or stopped breathing, and occasion-
ally convulsions and indications of brain damage.
Whooping cough is worldwide in distribution and
among the most acute infections of children. The disease
was first adequately described in 1578; undoubtedly it had
existed for a long time before that. About 100 years later,
the name pertussis (Latin: “intensive cough”) was intro-
duced in England. In 1906 at the Pasteur Institute, the
French bacteriologists Jules Bordet and Octave Gengou
isolated the bacterium that causes the disease. It was first
called the Bordet-Gengou bacillus, later Haemophilus per-
tussis, and still later Bordetella pertussis. The first pertussis
immunizing agent was introduced in the 1940s and soon
led to a drastic decline in the number of cases. Now
included in the DPT (diphtheria, tetanus, and pertussis)
vaccine, it confers active immunity against whooping
cough to children. Immunization is routinely begun at
two months of age and requires five shots for maximum
106
protection. A booster dose of pertussis vaccine should be

given between 15 and 18 months of age, and another
booster is given when the child is between four and six
years old. Later vaccinations are in any case thought to be
unnecessary, because the disease is much less severe when
it occurs in older children, especially if they have been
vaccinated in infancy.
The diagnosis of the disease is usually made on the
basis of its symptoms and is confirmed by specific cul-
tures. Treatment includes erythromycin, an antibiotic
that may help to shorten the duration of illness and the
period of communicability. Infants with the disease
require careful monitoring because breathing may tempo-
rarily stop during coughing spells. Sedatives may be
administered to induce rest and sleep, and sometimes the
use of an oxygen tent is required to ease breathing.
Psittacosis
Psittacosis, also known as ornithosis (or parrot fever), is
an infectious disease of worldwide distribution caused by
a bacterial parasite (Chlamydia psittaci) and transmitted to
humans from various birds. The infection has been found
in about 70 different species of birds; parrots and para-
keets (family Psittacidae, from which the disease is
named), pigeons, turkeys, ducks, and geese are the princi-
pal sources of human infection.
The association between the human disease and sick
parrots was first recognized in Europe in 1879, although
a thorough study of the disease was not made until 1929–
30, when severe outbreaks, attributed to contact with
imported parrots, occurred in 12 countries of Europe
and America. During the investigations conducted in
Germany, England, and the United States, the causative
agent was revealed. Strict regulations followed concerning
107
importation of psittacine birds, which undoubtedly

reduced the incidence of the disease but did not prevent
the intermittent appearance of cases. The infection was
later found in domestic stocks of parakeets and pigeons
and subsequently in other species. Infected turkeys, ducks,
or geese have caused many cases among poultry handlers
or workers in processing plants.
Psittacosis usually causes only mild symptoms of ill-
ness in birds, but in humans it can be fatal if untreated.
Humans usually contract the disease by inhaling dust par-
ticles contaminated with the excrement of infected birds.
The bacterial parasite thus gains access to the body and
multiplies in the blood and tissues. In humans psittacosis
may cause high fever and pneumonia. Other symptoms
include chills, weakness, head and body aches, and an ele-
vated respiratory rate. The typical duration of the disease
is two to three weeks, and convalescence often is pro-
tracted. Before modern antibiotic drugs were available,
the case fatality rate was approximately 20 percent, but
penicillin and the tetracycline drugs reduced this figure
almost to zero.
Pneumonia
Pneumonia is an inflammation and solidification of the
lung tissue as a result of infection, inhalation of foreign
particles, or irradiation. Many organisms, including viruses
and fungi, can cause pneumonia, but the most common
causes are bacteria, in particular species of Streptococcus
and Mycoplasma. Although viral pneumonia does occur,
viruses more commonly play a part in weakening the lung,
thus inviting secondary pneumonia caused by bacteria.
Fungal pneumonia can develop very rapidly and may be
fatal, but it usually occurs in hospitalized persons who,
because of impaired immunity, have reduced resistance to
108
infection. Contaminated dusts, when inhaled by previ-

ously healthy individuals, can sometimes cause fungal lung
diseases. Pneumonia can also occur as a hypersensitivity,
or allergic response, to agents such as mold, humidifiers,
and animal excreta or to chemical or physical injury (e.g.,
smoke inhalation).
Bacterial Pneumonia
Streptococcal pneumonia, caused by Streptococcus pneu-
moniae, is the single most common form of pneumonia,
especially in hospitalized patients. The bacteria may live
in the bodies of healthy persons and cause disease only
after resistance has been lowered by other illness or infec-
tion. Viral infections such as the common cold promote
streptococcal pneumonia by causing excessive secretion
of fluids in the respiratory tract. These fluids provide an
environment in which the bacteria flourish.
Patients with bacterial pneumonia typically expe-
rience a sudden onset of high fever with chills, cough,
chest pain, and difficulty in breathing. As the disease pro-
gresses, coughing becomes the major symptom. Sputum
discharge may contain flecks of blood. Any chest pains
result from the tenderness of the trachea (windpipe) and
muscles from severe coughing. Diagnosis usually can
be established by taking a culture of the organism from
the patient’s sputum and by chest X-ray examination.
Treatment is with specific antibiotics and supportive
care, and recovery generally occurs in a few weeks. In
some cases, however, the illness may become very severe,
and it is sometimes fatal, particularly in elderly people and
young children. Death from streptococcal pneumonia
is caused by inflammation and significant and extensive
bleeding in the lungs that results in the eventual cessa-
tion of breathing. Streptococcal bacteria release a toxin
called pneumolysin that damages the blood vessels in the
109
lungs, causing bleeding into the air spaces. Antibiotics

may exacerbate lung damage because they are designed
to kill the bacteria by breaking them open, which
leads to the further release of pneumolysin. Research
into the development of aerosol agents that stimulate
blood clotting and that can be inhaled into the lungs and
possibly be used in conjunction with traditional therapies
for streptococcal pneumonia is ongoing.
Mycoplasmal pneumonia, caused by Mycoplasma pneu-
moniae, an extremely small organism, usually affects
children and young adults; few cases beyond age 50 are
seen. Most outbreaks of this disease are confined to fami-
lies, small neighbourhoods, or institutions, although
epidemics can occur. M. pneumoniae grows on the mucous
membrane that lines the surfaces of internal lung struc-
tures; it does not invade the deeper tissues—muscle fibres,
elastic fibres, or nerves. The bacteria can produce an oxi-
dizing agent that might be responsible for some cell
damage. Usually the organism does not invade the mem-
brane that surrounds the lungs, but it does sometimes
inflame the bronchi and alveoli.
Another bacterium, Klebsiella pneumoniae, although it
has little ability to infect the lungs of healthy persons, pro-
duces a highly lethal pneumonia that occurs almost
exclusively in hospitalized patients with impaired immu-
nity. Other bacterial pneumonias include Legionnaire
disease, caused by Legionella pneumophilia; pneumonia sec-
ondary to other illnesses caused by Staphylococcus aureus
and Hemophilus influenzae; and psittacosis, an atypical
infectious form.
Viral and Fungal Pneumonia

Viral pneumonias are primarily caused by respiratory syn-
cytial, parainfluenza, and influenza viruses. Symptoms of
110
these pneumonias include runny nose, decreased appe-

tite, and low-grade fever, usually followed by respiratory
congestion and cough. Diagnosis is established by physi-
cal examination and chest X-rays. Nonbacterial pneumonia
is treated primarily with supportive care. In general, the
prognosis is excellent.
Tuberculosis should always be considered a possibil-
ity in any patient with pneumonia, and skin testing is
included in the initial examination of patients with lung
problems. Fungal infections such as coccidioidomycosis
and histoplasmosis should also be considered, particularly
if the patient was recently exposed to excavations, back-
yard swimming pools, old sheds or barns, or dust storms.
Other fungal and protozoan parasites (such as Pneumocystis
carinii ) are common in patients receiving immunosup-
pressive drugs or in patients with cancer, AIDS, or other
chronic diseases. Pneumocystis carinii pneumonia has been
one of the major causes of death among AIDS patients.
Hypersensitivity Pneumonia
Hypersensitivity pneumonias are a spectrum of disorders
that arise from an allergic response to the inhalation of
a variety of organic dusts. These pneumonias may occur
following exposure to moldy hay or sugarcane, room
humidifiers, and air-conditioning ducts, all of which con-
tain the fungus Actinomyces. Other fungi found in barley,
maple logs, and wood pulp may cause similar illnesses.
In addition, people exposed to rats, gerbils, pigeons,
parakeets, and doves may develop manifestations of
hypersensitivity pneumonia. Initially, these patients
experience fever with chills, cough, shortness of breath,
headache, muscle pain, and malaise, all of which may
subside in a day if there is no further exposure. A
more insidious form of hypersensitivity pneumonia is
111
associated with persistent malaise, fever, weight loss, and

cough. Diagnosis is established by medical history, physi-
cal examination, and specific laboratory tests. Treatment
consists of removing the patient from the offending envi-
ronment, bed rest, and supportive care.
Other Causes of Pneumonia

Pneumonia can also result from inhalation of oil droplets.
This type of disease, known as lipoid pneumonia, occurs
most frequently in workers exposed to large quantities of
oily mist and in the elderly. Oil that is being swallowed
may be breathed into the respiratory tract, or, less often, it
may come from the body itself when the lung is physically
injured. Scar tissue forms as a result of the presence of the
oil. Ordinarily no treatment is necessary.
Inflammation of lung tissues may result from X-ray
treatment of tumours within the chest. The disease makes
its appearance from 1 to 16 weeks after exposure to high-
dose X-rays has ceased. (The level of radiation in a routine
chest X-ray is too low to cause significant damage to liv-
ing tissue.) Recovery is usual unless too great an area of
lung tissue is involved.
Pneumonia in Immunocompromised Persons

For some years prior to 1980, it had been known that if the
immune system was compromised by immunosuppressive
drugs (given, for example, before organ transplantation to
reduce the rate of rejection), the patient was at risk for
developing pneumonia from organisms or viruses not nor-
mally pathogenic. Patients with AIDS may develop
pneumonia from cytomegalovirus or Pneumocystis infec-
tions, capable of causing invasive pneumonic lesions in
the setting of reduced immunity. Such infections are a
major cause of illness in these patients, are difficult to
treat, and may prove fatal. Infections with fungi such as
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Candida also occur. The diagnosis and management of

these cases has become a challenging and time-consuming
responsibility for respiratory specialists in locations with
large numbers of AIDS cases.
Legionnaire Disease
Legionnaire disease is a form of pneumonia caused by
the bacillus Legionella pneumophila. The name of the dis-
ease (and of the bacterium) is derived from a 1976 state
convention of the American Legion, a U.S. military vet-
erans’ organization, at a Philadelphia hotel where 182
Legionnaires contracted the disease, 29 of them fatally.
The largest known outbreak of Legionnaire disease, con-
firmed in more than 300 people, occurred in Murcia,
Spain, in 2001.
Typically, but not uniformly, the first symptoms of
Legionnaire disease are general malaise and headache, fol-
lowed by high fever, often accompanied by chills.
Coughing, shortness of breath, pleurisy-like pain, and
abdominal distress are common, and occasionally some
mental confusion is present. Although healthy individuals
can contract Legionnaire disease, the most common
patients are elderly or debilitated individuals or persons
whose immunity is suppressed by drugs or disease. People
who have cirrhosis of the liver caused by excessive inges-
tion of alcohol also are at higher risk of contracting the
disease.
Although it is fairly well documented that the disease is
rarely spread through person-to-person contact, the exact
source of outbreaks is often difficult to determine. It is sus-
pected that contaminated water in central air-conditioning
units can serve to disseminate L. pneumophila in droplets
into the surrounding atmosphere. Potable water and drain-
age systems are suspect, as is water at construction sites.
113
Once in the body, L. pneumophila enters the lungs, where

cells of the immune system called macrophages immediately
attempt to kill the bacteria by a process called phagocyto-
sis. However, L. pneumophila is able to evade phagocytosis
and take control of the macrophage to facilitate bacterial
replication. Eventually, the macrophage dies and bursts
open, releasing large numbers of bacteria into the lungs
and thus repeating the cycle of macrophage ingestion and
bacterial replication. In some cases, this cycle of infection
can lead to severe pneumonia, coma, and death.
Measurement of Legionella protein in the urine is a
rapid and specific test for detecting the presence of L.
pneumophila. Treatment for Legionnaire disease is with
antibiotics. Pontiac fever, an influenza-like illness charac-
terized by fever, headache, and muscle pain, represents a
milder form of Legionella infection.
Tuberculosis
Tuberculosis is an infectious disease that is caused by the
tubercle bacillus, Mycobacterium tuberculosis. In most forms
of the disease, the bacillus spreads slowly and widely in the
lungs, causing the formation of hard nodules (tubercles) or
large cheeselike masses that break down the respiratory
tissues and form cavities in the lungs. Blood vessels also
can be eroded by the advancing disease, causing the
infected person to cough up bright red blood.
During the 18th and 19th centuries, tuberculosis
reached near-epidemic proportions in the rapidly urban-
izing and industrializing societies of Europe and North
America. Indeed, “consumption,” as it was then known,
was the leading cause of death for all age groups in the
Western world from that period until the early 20th cen-
tury, at which time improved health and hygiene brought
about a steady decline in its mortality rates. Since the
114
Tuberculosis reached near-epidemic proportions in the 18th and 19th centu-

ries, but in areas with poor hygiene standards, it continues to be a fatal disease
continually complicated by drug-resistant strains. Fox Photos/Hulton
Archive/Getty Images
1940s, antibiotic drugs have reduced the span of treat-

ment to months instead of years, and drug therapy has
done away with the old TB sanatoriums where patients at
one time were nursed for years while the defensive prop-
erties of their bodies dealt with the disease.
Today, in less-developed countries where population is
dense and hygienic standards poor, tuberculosis remains a
major fatal disease. The prevalence of the disease has
increased in association with the HIV/AIDS epidemic; an
estimated one out of every four deaths from tuberculosis
involves an individual coinfected with HIV. In addition,
the successful elimination of tuberculosis as a major threat
to public health in the world has been complicated by the
115
rise of new strains of the tubercle bacillus that are resis-

tant to conventional antibiotics. Infections with these
strains are often difficult to treat and require the use of
combination drug therapies, sometimes involving the use
of five different agents.
The Course of Tuberculosis

The tubercle bacillus is a small, rod-shaped bacterium
that is extremely hardy; it can survive for months in a
state of dryness and can also resist the action of mild dis-
infectants. Infection spreads primarily by the respiratory
route directly from an infected person who discharges
live bacilli into the air. Minute droplets ejected by sneez-
ing, coughing, and even talking can contain hundreds of
tubercle bacilli that may be inhaled by a healthy person.
There the bacilli become trapped in the tissues of the body,
are surrounded by immune cells, and finally are sealed up
in hard, nodular tubercles. A tubercle usually consists of
a centre of dead cells and tissues, cheeselike (caseous)
in appearance, in which can be found many bacilli. This
centre is surrounded by radially arranged phagocytic (scav-
enger) cells and a periphery containing connective tissue
cells. The tubercle thus forms as a result of the body’s
defensive reaction to the bacilli. Individual tubercles are
microscopic in size, but most of the visible manifestations
of tuberculosis, from barely visible nodules to large tuber-
culous masses, are conglomerations of tubercles.
In otherwise healthy children and adults, the primary
infection often heals without causing symptoms. The bacilli
are quickly sequestered in the tissues, and the infected per-
son acquires a lifelong immunity to the disease. A skin test
taken at any later time may reveal the earlier infection and
the immunity, and a small scar in the lung may be visible
by X-ray. In this condition, sometimes called latent
116
tuberculosis, the affected person is not contagious. In

some cases, however, sometimes after periods of time that
can reach 40 years or more, the original tubercles break
down, releasing viable bacilli into the bloodstream. From
the blood the bacilli create new tissue infections else-
where in the body, most commonly in the upper portion
of one or both lungs. This causes a condition known
as pulmonary tuberculosis, a highly infectious stage of
the disease. In some cases the infection may break into the
pleural space between the lung and the chest wall, causing
a pleural effusion, or collection of fluid outside the lung.
Particularly among infants, the elderly, and immunocom-
promised adults (organ transplant recipients or AIDS
patients, for example), the primary infection may spread
through the body, causing miliary tuberculosis, a highly
fatal form if not adequately treated. In fact, once the
bacilli enter the bloodstream, they can travel to almost
any organ of the body, including the lymph nodes, bones
and joints, skin, intestines, genital organs, kidneys, and
bladder. An infection of the meninges that cover the brain
causes tuberculous meningitis; before the advent of spe-
cific drugs, this disease was always fatal, though most
affected people now recover.
The onset of pulmonary tuberculosis is usually insidi-
ous, with lack of energy, weight loss, and persistent cough.
These symptoms do not subside, and the general health
of the patient deteriorates. Eventually, the cough increases,
the patient may have chest pain from pleurisy, and there
may be blood in the sputum, an alarming symptom. Fever
develops, usually with drenching night sweats. In the lung,
the lesion consists of a collection of dead cells in which
tubercle bacilli may be seen. This lesion may erode a
neighbouring bronchus or blood vessel, causing the
patient to cough up blood (hemoptysis). Tubercular lesions
117
may spread extensively in the lung, causing large areas of

destruction, cavities, and scarring. The amount of lung tis-
sue available for the exchange of gases in respiration
decreases, and if untreated the patient will die from fail-
ure of ventilation and general toxemia and exhaustion.
Other Mycobacterial Infections

Another species of bacteria, M. bovis, is the cause of bovine
tuberculosis. M. bovis is transmitted among cattle and
some wild animals through the respiratory route, and it is
also excreted in milk. If the milk is ingested raw, M. bovis
readily infects humans. The bovine bacillus may be caught
in the tonsils and may spread from there to the lymph
nodes of the neck, where it causes caseation of the node
tissue (a condition formerly known as scrofula). The
node swells under the skin of the neck, finally eroding
through the skin as a chronic discharging ulcer. From the
gastrointestinal tract, M. bovis may spread into the blood-
stream and reach any part of the body. It shows, however,
a great preference for bones and joints, where it causes
destruction of tissue and eventually gross deformity.
Tuberculosis of the spine, or Pott disease, is characterized
by softening and collapse of the vertebrae, often resulting
in a hunchback deformity. Pasteurization of milk kills
tubercle bacilli, and this, along with the systematic identi-
fication and destruction of infected cattle, has led to the
disappearance of bovine tuberculosis in humans in many
countries.
The AIDS epidemic has given prominence to a group
of infectious agents known variously as nontuberculosis
mycobacteria, atypical mycobacteria, and mycobacteria
other than tuberculosis (MOTT). This group includes
such Mycobacterium species as M. avium (or M. avium-
intracellulare), M. kansasii, M. marinum, and M. ulcerans.
118
These bacilli have long been known to infect animals and

humans, but they cause dangerous illnesses of the lungs,
lymph nodes, and other organs only in people whose
immune systems have been weakened. Among AIDS
patients, atypical mycobacterial illnesses are common
complications of HIV infection. Treatment is attempted
with various drugs, but the prognosis is usually poor owing
to the AIDS patient’s overall condition.
Diagnosis and Treatment of Tuberculosis

The diagnosis of pulmonary tuberculosis depends on
finding tubercle bacilli in the sputum, in the urine, in gas-
tric washings, or in the cerebrospinal fluid. The primary
method used to confirm the presence of bacilli is a spu-
tum smear, in which a sputum specimen is smeared onto a
slide, stained with a compound that penetrates the organ-
ism’s cell wall, and examined under a microscope. If bacilli
are present, the sputum specimen is cultured on a special
medium to determine whether the bacilli are M. tuber-
culosis. An X-ray of the lungs may show typical shadows
caused by tubercular nodules or lesions. The prevention
of tuberculosis depends on good hygienic and nutritional
conditions and on the identification of infected patients
and their early treatment. A vaccine, known as BCG vac-
cine, is composed of specially weakened tubercle bacilli.
Injected into the skin, it causes a local reaction, which
confers some immunity to infection by M. tuberculosis for
several years. It has been widely used in some countries
with success; its use in young children in particular has
helped to control infection in the developing world. The
main hope of ultimate control, however, lies in preventing
exposure to infection, and this means treating infectious
patients quickly, possibly in isolation until they are nonin-
fectious. In many developed countries, individuals at risk
119
for tuberculosis, such as health care workers, are regularly

given a skin test (tuberculin test) to show whether they
have had a primary infection with the bacillus.
Today, the treatment of tuberculosis consists of drug
therapy and methods to prevent the spread of infectious
bacilli. Historically, treatment of tuberculosis consisted of
long periods, often years, of bed rest and surgical removal
of useless lung tissue. In the 1940s and ’50s several anti-
microbial drugs were discovered that revolutionized
the treatment of patients with tuberculosis. As a result,
with early drug treatment, surgery is rarely needed. The
most commonly used antituberculosis drugs are isonia-
zid and rifampicin (rifampin). These drugs are often used
in various combinations with other agents, such as eth-
ambutol, pyrazinamide, or rifapentine, in order to avoid
the development of drug-resistant bacilli. Patients with
strongly suspected or confirmed tuberculosis undergo an
initial treatment period that lasts two months and con-
sists of combination therapy with isoniazid, rifampicin,
ethambutol, and pyrazinamide. These drugs may be given
daily or two times per week. The patient is usually made
noninfectious quite quickly, but complete cure requires
continuous treatment for another four to nine months.
The length of the continuous treatment period depends
on the results of chest X-rays and sputum smears taken
at the end of the two-month period of initial therapy.
Continuous treatment may consist of once daily or twice
weekly doses of isoniazid and rifampicin or isoniazid and
rifapentine.
If a patient does not continue treatment for the
required time or is treated with only one drug, bacilli will
become resistant and multiply, making the patient sick
again. If subsequent treatment is also incomplete, the sur-
viving bacilli will become resistant to several drugs.
120
Multidrug-resistant tuberculosis (MDR TB) is a form of

the disease in which bacilli have become resistant to iso-
niazid and rifampicin. MDR TB is treatable but is
extremely difficult to cure, typically requiring two years of
treatment with agents known to have more severe side
effects than isoniazid or rifampicin. Extensively drug-
resistant tuberculosis (XDR TB) is a rare form of MDR
TB. XDR TB is characterized by resistance to not only
isoniazid and rifampin but also a group of bactericidal
drugs known as fluoroquinolones and at least one amino-
glycoside antibiotic, such as kanamycin, amikacin, or
capreomycin. Aggressive treatment using five different
drugs, which are selected based on the drug sensitivity of
the specific strain of bacilli in a patient, has been shown to
be effective in reducing mortality in roughly 50 percent of
XDR TB patients. In addition, aggressive treatment can
help prevent the spread of strains of XDR TB bacilli.
In 1995, in part to prevent the development and spread
of MDR TB, the World Health Organization began
encouraging countries to implement a compliance pro-
gram called directly observed therapy (DOT). Instead of
taking daily medication on their own, patients are directly
observed by a clinician or responsible family member
while taking larger doses twice a week. Although some
patients consider DOT invasive, it has proved successful
in controlling tuberculosis.
121
CHAPTER5
DISEASES AND DISORDERS
OF THE RESPIRATORY SYSTEM
T here exists a wide variety of noninfectious diseases

and disorders of the human respiratory system.
These conditions can be classified according to the spe-
cific anatomical regions of the respiratory tract that they
affect. Thus, there are diseases of the upper airways; dis-
eases of the pleura; diseases of the larynx, trachea,
bronchial tree, and lungs; and diseases of the mediastinum
and diaphragm. Although these divisions provide a gen-
eral outline of the ways in which diseases may affect the
lung, they are by no means rigid. It is common for more
than one part of the system to be involved in any particu-
lar disease process, and disease in one region frequently
leads to involvement of other parts.
Important examples of diseases and disorders of the
respiratory system include sleep apnea, emphysema, and
cystic fibrosis. Many noninfectious respiratory conditions
are chronic and thus may ultimately result in progressive
deficiency in respiratory function. The causes of the vari-
ous diseases and disorders are diverse, ranging from
inherited genetic mutations to smoking to trauma.
Treatment for this group of conditions is similarly varied,
and in many cases therapy may include not only the admin-
istration of medications but invasive surgery as well.
diseases of the upper airway

The nose, sinuses, palate, and nasopharynx are all suscep-
tible to disease. Conditions affecting these tissues may
122
7 Diseases and Disorders of the Respiratory System 7
result from a number of different causes, such as congeni-

tal structural abnormalities or malignant neoplastic
changes (i.e., cancer). Such cancers are typically more
common in smokers than in nonsmokers.
Snoring
Snoring is a rough, hoarse noise produced upon the intake
of breath during sleep and caused by the vibration of the
soft palate and vocal cords. It is often associated with
obstruction of the nasal passages, which necessitates
breathing through the mouth. Snoring is more common in
the elderly because the loss of tone in the oropharyngeal
Although snoring bears the brunt of many jokes, loud interrupted snoring
can indicate sleep apnea, a potentially life-threatening condition. © www
.istockphoto.com / Stephanie Horrocks
123
musculature promotes vibration of the soft palate and

pharynx. It is also more common in men than in women,
and it occurs most often in obese persons. Children’s snor-
ing usually results from enlarged tonsils or adenoids.
Whatever the cause, snoring is always associated with
mouth breathing and can be corrected by removing
obstructions to normal nasal breathing or by altering
sleeping position so that the affected individual does not
lie on his back. Loud interrupted snoring is a regular
feature of sleep apnea, a common and potentially life-
threatening condition that generally requires treatment.
Sleep Apnea
Sleep apnea is a respiratory condition characterized by
pauses in breathing during sleep. The word apnea is derived
from the Greek apnoia, meaning “without breath.” There
are three types of sleep apnea: obstructive, which is the
most common form and involves the collapse of tissues of
the upper airway; central, which is very rare and results
from failure of the central nervous system to activate
breathing mechanisms; and mixed, which involves charac-
teristics of both obstructive and central apneas. In
obstructive sleep apnea (OSA), airway collapse is eventu-
ally terminated by a brief awakening, at which point the
airway reopens and the person resumes breathing. In
severe cases this may occur once every minute during
sleep and in turn may lead to profound sleep disruption.
In addition, repetitive interruption of normal breathing
can lead to a reduction in oxygen levels in the blood.
Obstructive sleep apnea is most often caused by exces-
sive fat in the neck area. Thus, the condition has a strong
association with certain measures of obesity, such as neck
size, body weight, or body-mass index. In men shirt size is
a useful predictor, with the likelihood of OSA increasing
124
with a collar greater than about 42 cm (16.5 inches). Other

causes of the condition include medical disorders, such as
hypothyroidism or tonsillar enlargement. The condition
is also more common in patients with a set-back chin (ret-
rognathia), and it may be for this reason that patients of
East Asian heritage are more likely to have sleep apnea
without being overweight.
The most common symptom of OSA is sleepiness,
with many patients describing sleep as unrefreshing.
Sleep disturbance may cause difficulty concentrating,
worsen short-term memory, and increase irritability. The
bed partner is likely to describe heavy snoring (OSA is
exceptionally unusual without snoring) and may have
observed the apneic pauses, with the resumption of
breathing usually described as a gasp or a snort. Patients
with OSA and sleepiness are at increased risk of motor
vehicle accidents; the magnitude of the increased risk is
the subject of some debate but is thought to be between
three- and sevenfold. The risk returns to normal after
treatment. Patients with severe OSA—those who stop
breathing more often than once every two minutes—are
at risk of other diseases, including ischemic heart disease,
hypertension, and insulin resistance. However, it is less
certain that these diseases are caused by OSA; it is more
likely that they are secondary consequences of obesity
and a sedentary lifestyle.
Treatment typically involves continuous positive air-
way pressure (CPAP), which uses a mask (facial or nasal)
during sleep to blow air into the upper airway. Although
CPAP does not treat the condition itself, which can be
resolved only by weight loss or treatment of underlying
conditions, it does prevent airway collapse and thus
relieves daytime sleepiness. Some patients with sleep
apnea may be treated with a dental device to advance the
lower jaw, though surgery is seldom recommended.
125
Pickwickian Syndrome
Pickwickian syndrome, also known as obesity hypoventi-

lation syndrome, is a complex of respiratory and circulatory
symptoms associated with extreme obesity. The name
originates from the fat boy depicted in Charles Dickens’s
The Pickwick Papers, who showed some of the same traits.
(By some definitions, to be obese is to exceed one’s ideal
weight by 20 percent or more; an extremely obese person
would exceed the optimum weight by a much larger per-
centage.) This condition often occurs in association with
sleep apnea.
In pickwickian syndrome the rate of breathing is
chronically decreased below the normal level. Because of
inadequate removal of carbon dioxide by the lungs, levels
of carbon dioxide in the blood increase, leading to respira-
tory acidosis. In more severe instances, oxygen in the
blood is also significantly reduced.
Individuals who have pickwickian syndrome often com-
plain of slow thinking, drowsiness, and fatigue. Low blood
oxygen causes the small blood vessels entering the lungs to
constrict, thus increasing pressure in the vessels that supply
the lungs. The elevated pressure stresses the right ventricle
of the heart, ultimately causing right heart failure. Finally,
excessive fluid accumulates throughout the body (periph-
eral edema), especially beneath the skin of the lower legs.
Diseases of the pleura

The most common disease of the pleura is caused by
inflammation and is referred to as pleurisy. Other condi-
tions of the pleura may arise from inflammatory or
neoplastic processes that lead to fluid accumulation (pleu-
ral effusion) between the two pleural layers, in the space
known as the pleural cavity. The pleural membranes of the
126
lungs are also vulnerable to perforation and spontaneous

rupture, enabling air to enter the pleural cavity. This causes
spontaneous pneumothorax, a partial or occasionally
complete collapse of the lung. Mesothelioma, a cancer of
the pleura, may occur many years after inhalation of asbes-
tos fibres. The cancerous cells of the pleura can eventually
metastasize and invade nearby and distant tissues, includ-
ing tissues of the neck and head.
Pleurisy
Pleurisy, also called pleuritis, is an inflammation of the
pleura, the membranes that line the thoracic cavity and
fold in to cover the lungs. Pleurisy may be characterized as
dry or wet. In dry pleurisy, little or no abnormal fluid accu-
mulates in the pleural cavity, and the inflamed surfaces of
the pleura produce an abnormal sound called a pleural
friction rub when they rub against one another during res-
piration. This rubbing may be felt by the affected person
or heard through a stethoscope applied to the surface of
the chest. In wet pleurisy, fluids produced by the inflamed
tissues accumulate within the pleural cavity, sometimes in
quantities sufficient to compress the underlying lung and
cause shortness of breath.
Because the pleura is well supplied with nerves, pleu-
risy can be very painful. Pleurisy is commonly caused by
infection in the underlying lung and, rarely, by diffuse
inflammatory conditions such as lupus erythematosus.
Treatment of pleurisy includes pain relief, fluid evacua-
tion, and treatment of the underlying disease.
Pleural Effusion and Thoracic Empyema

Pleural effusion, or hydrothorax, is an accumulation of
watery fluid in the pleural cavity. There are many causes of
127
pleural effusion, including pneumonia, tuberculosis, and

the spread of a malignant tumour from a distant site
to the pleural surface. Pleural effusion often develops as a
result of chronic heart failure because the heart cannot
pump fluid away from the lungs, and fluid that seeps from
the lungs places additional stress on the dysfunctioning
heart. Large pleural effusions can cause disabling short-
ness of breath.
If symptoms of pleural effusion develop, a tube is
inserted through the chest wall into the pleural space to
drain the fluid. Under certain conditions, such as malig-
nant disease of the pleura (i.e., mesothelioma), pleural
effusion can be treated by introducing an irritating sub-
stance called a sclerosing agent into the pleural space in
order to stimulate an inflammatory reaction of the pleural
surfaces. As the inflammation heals, tissue adhesions
obliterate the pleural space, thereby preventing the accu-
mulation of more fluid. Examples of sclerosing agents that
cause an inflammatory reaction of the pleural surfaces
include talc, doxycycline, and bleomycin.
The accumulation of pus in the pleural cavity is known
as thoracic empyema, or pyothorax. This condition is
often the result of a microbial, usually bacterial, infection
within the pleural cavity. The most common cause is lung
inflammation (pneumonia) resulting in the spread of
infection from the lung to the bordering pleural mem-
brane. It may also be caused by a lung abscess or some
forms of tuberculosis. When the bronchial tree is involved
in the infection, air may get into the pleural cavity. The
presence of both air and pus inside the pleural cavity is
known as pneumothorax.
Thoracic empyema may be characterized by fever,
coughing, shortness of breath, and weight loss, and the
presence of fluid as ascertained by a chest X-ray. Treatment
is directed at drainage of small amounts of pus through
128
a needle or larger amounts through a drainage tube.

Video-assisted thoracic surgery or open-chest surgery is
sometimes needed to eviscerate thick or compartmental-
ized pus from the pleural space. Antibiotics are used to
treat the underlying infection.
Pneumothorax
Pneumothorax is a condition in which air accumulates
in the pleural space, causing it to expand and thus com-
press the underlying lung, which may then collapse.
There are three major types of pneumothorax: trau-
matic pneumothorax, spontaneous pneumothorax, and
tension pneumothorax.
Traumatic pneumothorax is the accumulation of air
caused by penetrating chest wounds (knife stabbing, gun-
shot) or other injuries to the chest wall, after which air is
sucked through the opening and into the pleural sac.
Spontaneous pneumothorax is the passage of air into the
pleural sac from an abnormal connection created between
the pleura and the bronchial system as a result of bullous
emphysema or some other lung disease. The symptoms of
spontaneous pneumothorax are a sharp pain in one side
of the chest and shortness of breath.
Tension pneumothorax is a life-threatening condition
that can occur as a result of trauma, lung infection, or
medical procedures, such as high-pressure mechanical
ventilation, chest compression during cardiopulmonary
resuscitation (CPR), or thoracoscopy (closed-lung biopsy).
In contrast to traumatic pneumothorax and spontaneous
pneumothorax, in tension pneumothorax air that becomes
trapped in the pleural space cannot escape. As a result,
with each breath the patient inhales, air and pressure
accumulate within the chest. When the lung on the
affected side of the chest collapses, the heart, blood
129
vessels, and airways are pushed to the centre of the chest,

thereby compressing the other lung. This leads to
decreases in blood pressure, consciousness, and breathing
that in turn may lead to shock and death.
Most pneumothoraxes can be treated by inserting a
tube through the chest wall. This procedure allows air to
escape from the chest cavity, which enables the lung to re-
expand. In some cases, a catheter connected to a vacuum
system is required to re-expand the lung. While small
pneumothoraxes may resolve spontaneously, others may
require surgery to prevent recurrences.
Diseases of the
bronchi and lungs
Diseases of the bronchi and lungs are often associated
with significant impairments in respiration. In fact, many
of these conditions are associated with irreversible lung
damage. Whereas several diseases of the bronchi and
lungs, including bronchiectasis and cystic fibrosis, may be
present in childhood, others (such as pulmonary emphy-
sema and chronic obstructive pulmonary disease) occur in
adulthood and are frequently associated with excessive
exposure to tobacco smoke.
Bronchiectasis
Bronchiectasis is believed to usually begin in childhood,
possibly after a severe attack of pneumonia. It consists of
a dilatation of major bronchi. The bronchi become chron-
ically infected, and excess sputum production and
episodes of chest infection are common. In some cases,
clubbing (swelling of the fingertips and, occasionally, of
the toes) may occur. The disease may also develop as a
consequence of airway obstruction or of undetected (and
130
therefore untreated) aspiration into the airway of small

foreign bodies, such as parts of plastic toys. Bronchiectasis
may also develop as a consequence of inherited condi-
tions, of which the most important is the familial disease
cystic fibrosis.
Management of the condition includes antibiotics to
fight lung infections, medications to dilate the airways
and to relieve pain, enzyme therapy to thin the mucus, and
postural drainage and percussion to loosen mucus in the
lungs so it can be expelled through coughing. These thera-
pies, in addition to others, have helped control pulmonary
infections and have markedly improved survival in affected
persons, many of whom, who would formerly have died in
childhood, now reach adult life.
Chronic Bronchitis
The chronic cough and sputum production of chronic
bronchitis were once dismissed as nothing more than
“smoker’s cough,” without serious implications. But the
striking increase in mortality from chronic bronchitis and
emphysema that occurred after World War II in all
Western countries indicated that the long-term conse-
quences of chronic bronchitis could be serious. This
common condition is characteristically produced by ciga-
rette smoking. After about 15 years of smoking, significant
quantities of mucus are coughed up in the morning, due
to an increase in size and number of mucous glands lining
the large airways. The increase in mucous cells and the
development of chronic bronchitis may be enhanced by
breathing polluted air. For example, chronic bronchitis is
sometimes caused by prolonged inhalation of environ-
mental irritants, particularly in areas of uncontrolled coal
burning, or of organic substances such as hay dust. In
some countries chronic bronchitis is caused by daily
131
inhalation of wood smoke from improperly ventilated

cooking stoves.
The changes are not confined to large airways, though
these produce the dominant symptom of chronic sputum
production. Changes in smaller bronchioles lead to oblit-
eration and inflammation around their walls. All these
changes together, if severe enough, can lead to distur-
bances in the distribution of ventilation and perfusion in
the lung, causing a fall in arterial oxygen tension and a
rise in carbon dioxide tension. By the time this occurs,
the ventilatory ability of the patient, as measured by the
velocity of a single forced expiration, is severely compro-
mised; in a cigarette smoker, ventilatory ability has
usually been declining rapidly for some years. It is not
clear what determines the severity of these changes.
Some people can smoke for decades without evidence of
significant airway changes, whereas others may experi-
ence severe respiratory compromise after 15 years or less
of exposure. Smoking-related chronic bronchitis often
occurs in association with emphysema; the coexistence
of these two conditions is known as chronic obstructive
pulmonary disease.
For current smokers the most important treatment
of chronic bronchitis is the cessation of smoking. The
mucus-producing cough will subside within weeks or
months and may resolve altogether. Unfortunately, nar-
rowing of the bronchi and obstruction of airflow may
continue to progress even after smoking ceases, though
the rate of progression generally slows. Because the dam-
age to the bronchial tree is largely irreversible, treatment
is mainly symptomatic, consisting of expectorants and
bronchodilators. Occasionally, drugs to suppress parox-
ysmal coughing may be necessary, but they must be used
sparingly because they can be addictive and because
expectoration is necessary. Of primary importance is
132
the prevention of superimposed infections, either by

careful watching for early signs or by using prophylactic
antibiotics. Adjusting the patient’s living and working
environments to the largely irreversible condition is an
essential factor in treatment.
Pulmonary Emphysema
This irreversible disease consists of destruction of alveo-
lar walls. It occurs in two forms, centrilobular emphysema,
in which the destruction begins at the centre of the lob-
ule, and panlobular (or panacinar) emphysema, in which
alveolar destruction occurs in all alveoli within the lobule
simultaneously. In advanced cases of either type, this dis-
tinction can be difficult to make. Centrilobular emphysema
is the form most commonly seen in cigarette smokers, and
some observers believe it is confined to smokers. It is
more common in the upper lobes of the lung (for unknown
reasons). By the time the disease has developed, some
impairment of ventilatory ability has probably occurred.
Panacinar emphysema may also occur in smokers, but it is
the type of emphysema characteristically found in the
lower lobes of patients with a deficiency in the antiproteo-
lytic enzyme known as alpha-1 antitrypsin. Similar to
centrilobular emphysema, panacinar emphysema causes
ventilatory limitation and eventually blood gas changes.
Other types of emphysema, of less importance than the
two major varieties, may develop along the dividing walls
of the lung (septal emphysema) or in association with scars
from other lesions.
A major step forward in understanding the develop-
ment of emphysema followed the identification, in
Sweden, of families with an inherited deficiency of alpha-1
antitrypsin, an enzyme essential for lung integrity.
Members of affected families who smoked cigarettes
133
Emphysema destroys the walls of the alveoli of the lungs, resulting in a loss
of surface area available for the exchange of oxygen and carbon dioxide dur-
ing breathing. This produces symptoms of shortness of breath, coughing, and
wheezing. In severe emphysema, difficulty in breathing leads to decreased oxy-
gen intake, which causes headaches and symptoms of impaired mental ability.
commonly developed panacinar emphysema in the lower

lobes, unassociated with chronic bronchitis but leading to
ventilatory impairment and disability. Intense investiga-
tion of this major clue led to the “protease-antiprotease”
theory of emphysema. It is postulated that cigarette smok-
ing either increases the concentration of protease enzymes
released in the lung (probably from white blood cells) or
impairs the lung’s defenses against these enzymes or both.
Although many details of the essential biochemical steps
at the cellular level remain to be clarified, this represents a
major step forward in understanding a disease whose
134
genesis was once ascribed to overinflation of the lung (like

overdistending a bicycle tire).
Chronic bronchitis and emphysema are distinct pro-
cesses. Both may follow cigarette smoking, however, and
they commonly occur together, so determination of the
extent of each during life is not easy. In general, significant
emphysema is more likely if ventilatory impairment is
constant, gas transfer in the lung (usually measured with
carbon monoxide) is reduced, and the lung volumes are
abnormal. Development of high-resolution computerized
tomography has greatly improved the accuracy of detec-
tion of emphysema. Some people with emphysema suffer
severe incapacity before age 60. Thus, emphysema is not a
disease of the elderly only. An accurate diagnosis can be
made from pulmonary function tests, careful radiological
examination, and a detailed history. The physical exami-
nation of the chest reveals evidence of airflow obstruction
and overinflation of the lung, but the extent of lung
destruction cannot be reliably gauged from these signs,
and therefore laboratory tests are required.
The prime symptom of emphysema, which is always
accompanied by a loss of elasticity of the lung, is shortness
of breath, initially on exercise only, and associated with
loss of normal ventilatory ability and increased obstruc-
tion to expiratory airflow. The expiratory airflow from a
maximum inspiration is measured by the “forced expira-
tory volume in one second,” or FEV1, and is a predictor of
survival of emphysema. Chronic hypoxemia (lowered oxy-
gen tension) often occurs in severe emphysema and leads
to the development of increased blood pressure in the
pulmonary circulation, which in turn leads to failure of
the right ventricle of the heart. The symptoms and signs
of right ventricular failure include swelling of the ankles
(edema) and engorgement of the neck veins. These are
portents of advanced lung disease in this condition. The
135
hypoxemia may also lead to an increase in total hemoglo-

bin content and in the number of circulating red blood
cells, as well as to psychological depression, irritability,
loss of appetite, and loss of weight. Thus, the advanced
syndrome of chronic obstructive lung disease may cause
such shortness of breath that the afflicted person has dif-
ficulty walking, talking, and dressing, as well as numerous
other symptoms.
The slight fall in ventilation that normally accompa-
nies sleep may exacerbate the failure of lung function in
chronic obstructive lung disease, leading to a further fall
in arterial oxygen tension and an increase in pulmonary
arterial pressure. Unusual forms of emphysema also
occur. In one form the disease appears to be unilateral,
involving one lung only and causing few symptoms.
Unilateral emphysema is believed to result from a severe
bronchiolitis in childhood that prevented normal matu-
ration of the lung on that side. “Congenital lobar
emphysema” of infants is usually a misnomer, since there
is no alveolar destruction. It is most commonly caused by
overinflation of a lung lobe due to developmental malfor-
mation of cartilage in the wall of the major bronchus.
Such lobes may have to be surgically removed to relieve
the condition. Bullous emphysema can occur in one or
both lungs and is characterized by the presence of one
or several abnormally large air spaces surrounded by rela-
tively normal lung tissue. This disease most commonly
occurs between ages 15 and 30 and usually is not recog-
nized until a bullous air space leaks into the pleural space,
causing a pneumothorax.
Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a
progressive respiratory disease characterized by the
136
combination of signs and symptoms of emphysema and

bronchitis. It is a common disease, and each year about
30,000 people in the United Kingdom and roughly
119,000 people in the United States die from COPD.
Sources of noxious particles that can cause COPD include
tobacco smoke, air pollution, and the burning of certain
fuels in poorly ventilated areas. In rare cases COPD has
been associated with a genetic defect that results in defi-
ciency of alpha-1 antitrypsin. Although primarily a lung
disease, it is increasingly recognized that COPD has sec-
ondary associations, including muscle weakness and
osteoporosis. Identifying and treating these secondary
problems via pulmonary rehabilitation (supervised exer-
cise) and other methods may improve the functional
status of the lungs.
COPD is distinguished pathologically by the destruc-
tion of lung tissue, which is replaced by holes characteristic
of emphysema, and by a tendency for excessive mucus
production in the airway, which gives rise to symptoms of
bronchitis. These pathological characteristics are realized
physiologically as difficulty in exhaling (called flow limita-
tion), which causes increased lung volume and manifests
as breathlessness. Other early symptoms of the condition
include a “smoker’s cough” and daily sputum production.
Coughing up blood is not a feature of COPD and when
present raises concern about a second, tobacco-related
condition, particularly lung cancer. Patients with COPD
are vulnerable to episodic worsening of their condition
(called exacerbation). Exacerbations are triggered by
infection, either bacterial or viral. Therefore, antibiotics,
which work against bacteria, are not always required.
Frequent exacerbations, particularly if severe enough to
warrant hospital admission, indicate a poor prognosis.
The only therapeutic intervention shown to alter the
course of COPD is removal of the noxious trigger, which
137
can be accomplished in most cases by cessation of smok-

ing. Treatments used in the early stages of disease include
vaccination against influenza and pneumococcal pneu-
monia and administration of drugs that widen the
airways (i.e., bronchodilators). Inhaled corticosteroids
are commonly prescribed, especially for patients with
frequent exacerbations. Short courses (typically five
days) of oral corticosteroids are given for exacerbations
but generally are not used in the routine management of
COPD. A six- to eight-week course of pulmonary reha-
bilitation often benefits patients who have symptoms
despite inhaler therapy. This should be followed by a
community/home maintenance program or by repeat
courses every two years.
In COPD patients with low blood–oxygen levels, the
prescription of home oxygen can reduce hospital admis-
sion and extend survival but does not alter the progression
of lung disease. Some COPD patients do not find oxygen
attractive, since they need to use it for 16 hours each day
to derive benefit, which leads to further difficulties in
mobility. In addition, oxygen is extremely flammable, and
the prescription of oxygen for patients who smoke remains
controversial because of the risk for explosion. Specialized
centres can offer treatments for patients with advanced
disease, including noninvasive ventilation and surgical
options (i.e., lung transplantation and lung-volume
reduction).
Lung Congestion
Lung congestion is characterized by distention of blood
vessels in the lungs and filling of the alveoli with blood as a
result of an infection, high blood pressure, or cardiac
insufficiencies (i.e., inability of the heart to function ade-
quately). Active congestion of the lungs is caused by
138
infective agents or irritating gases, liquids, and particles.

The alveolar walls and the capillaries in them become dis-
tended with blood. Passive congestion is due either to
high blood pressure in the capillaries, caused by a cardiac
disorder, or to relaxation of the blood capillaries followed
by blood seepage.
Left-sided heart failure—inability of the left side of
the heart to pump sufficient blood into the general circu-
lation—causes back pressure on the pulmonary vessels
delivering oxygenated blood to the heart. The blood pres-
sure becomes high in the alveolar capillaries, and they
begin to distend. Eventually the pressure becomes too
great, and blood escapes through the capillary wall into
the alveoli, flooding them. Mitral stenosis, narrowing of
the valve between the upper and lower chambers in the
left side of the heart, causes chronic passive congestion.
Iron pigment from the blood that congests the alveoli
spreads throughout the lung tissue and causes deteriora-
tion of tissue and formation of scar tissue. The walls of the
alveoli also thicken and gas exchange is greatly impaired.
The affected person shows difficulty in breathing, there is
a bloody discharge, and the skin takes on a bluish tint as
the disease progresses.
Passive congestion caused by relaxation of the blood
vessels occurs in bedridden patients with weak heart
action. Blood accumulates in the lower part of the lungs,
although there is usually enough unaffected lung tissue for
respiration. The major complication arises in mild cases of
pneumonia, when the remaining functioning tissue
becomes infected.
Pulmonary edema is much the same as congestion
except that the substance in the alveoli is the watery
plasma of blood, rather than whole blood, and the
precipitating causes may somewhat differ. Inflammatory
edema results from influenza or bacterial pneumonia. In
139
X-ray showing lung congestion caused by congestive heart failure. Dr.

Thomas Hooten/Centers for Disease Control and Prevention (CDC)
(Image Number: 6241)
140
mechanical edema the capillary permeability is broken

down by the same type of heart disorders and irritants as
in congestion. It can occur, for unknown reasons, after
reinflation of a collapsed lung. After an operation, if too
great a volume of intravenous fluids is given, the blood
pressure rises and edema ensues. Excessive irradiation and
severe allergic reactions may also produce this disorder.
The lungs become pale, wet, enlarged, and heavy. It
may take only one or two hours for two to three quarts of
liquid to accumulate. Acute cases can be fatal in 10 to 20
minutes. A person with pulmonary edema experiences dif-
ficulty in breathing, with deep gurgling rattles in the
throat. The person’s skin turns blue, and, because he or
she is too weak to clear the fluids, the person may actually
drown in the lung secretions.
Atelectasis
Atelectasis is characterized primarily by the absence of air
in the lungs. The term is derived from the Greek words
atelēs and ektasis, literally meaning “incomplete expansion”
in reference to the lungs. The term atelectasis can also be
used to describe the collapse of a previously inflated lung,
either partially or fully, because of specific respiratory dis-
orders. There are three major types of atelectasis: adhesive,
compressive, and obstructive.
Adhesive atelectasis is seen in premature infants who
are unable to spontaneously breathe and in some infants
after only a few days of developing breathing difficulties;
their lungs show areas in which the alveoli, or air sacs, are
not expanded with air. These infants usually suffer from a
disorder called respiratory distress syndrome, in which
the surface tension inside the alveolus is altered so
that the alveoli are perpetually collapsed. This is typically
caused by a failure to develop surface-active material
141
X-ray showing changes in the right upper pulmonary lung field that are
characteristic of atelectasis. Dr. Thomas Hooten/Centers for Disease
Control and Prevention (CDC) (Image Number: 6242)
142
(surfactant) in the lungs. Treatment for infants with this

syndrome includes replacement therapy with surfactant.
Compressive atelectasis is caused by an external pres-
sure on the lungs that drives the air out. Collapse is
complete if the force is uniform or is partial when the
force is localized. Local pressure can result from tumour
growths, an enlarged heart, or elevation of the diaphragm.
The ducts and bronchi leading to the alveoli are squeezed
together by the pressure upon them.
Obstructive atelectasis may be caused by foreign
objects lodged in one of the major bronchial passage-
ways, causing air trapped in the alveoli to be slowly
absorbed by the blood. It may also occur as a complica-
tion of abdominal surgery. The air passageways in the
lungs normally secrete a mucous substance to trap dust,
soot, and bacterial cells, which frequently enter with
inhaled air. When a person undergoes surgery, the anes-
thetic stimulates an increase in bronchial secretions.
Generally, if these secretions become too abundant, they
can be pushed out of the bronchi by coughing or strong
exhalation of air. After abdominal surgery, the breathing
generally becomes more shallow because of the sharp
pain induced by the breathing movements, and the mus-
cles beneath the lungs may be weakened. Mucous plugs
can result that cause atelectasis. Other causes of obstruc-
tion include tumours or infection.
The symptoms in extreme atelectasis include low blood
oxygen content, which manifests as a bluish tint to the skin,
absence of respiratory movement on the side involved,
displacement of the heart toward the affected side, and
consolidation of the lungs into a smaller mass. If a lung
remains collapsed for a long period, the respiratory tissue is
replaced by fibrous scar tissue, and respiratory function can-
not be restored. Treatment for obstructive and compressive
143
atelectasis is directed toward removal of any obstruction or

compressive forces.
Lung Infarction
Lung infarction is the death of one or more sections
of lung tissue due to deprivation of an adequate blood
supply. The section of dead tissue is called an infarct. The
cessation or lessening of blood flow results ordinarily from
an obstruction in a blood vessel that serves the lung. The
obstruction may be a blood clot that has formed in a dis-
eased heart and has traveled in the bloodstream to the
lungs, or air bubbles in the bloodstream (both of these are
instances of embolism), or the blockage may be by a clot
that has formed in the blood vessel itself and has remained
at the point where it was formed (such a clot is called a
thrombus). Ordinarily, when the lungs are healthy, such
blockages fail to cause death of tissue because the blood
finds its way by alternative routes. If the lung is congested,
infected, or inadequately supplied with air, however, lung
infarctions can follow blockage of a blood vessel.
Because neither the lung tissue nor the pleural sac sur-
rounding the lungs has sensory endings, infarcts that occur
deep inside the lungs produce no pain; those extending to
the outer surface cause fluids and blood to seep into the
space between the lungs and the pleural sac. The sac dis-
tends with the excess fluid and there may be difficulty in
inflating the lungs. When pain is present it indicates pleu-
ral involvement. The pain may be localized around the rib
cage, shoulders, and neck, or it may be lower, near the
muscular diaphragm that separates the chest cavity from
the abdomen. One explanation for the pain is that it is
from tension on the sensitive nerve endings in the mem-
brane lining the chest. Pain is most severe on inhalation.
144
The symptoms of infarcts are generally spitting up of

blood, coughing, fever, moderate difficulty in breathing,
increased heartbeat, pleural rubbing, diminished breath
sounds, and a dull sound heard when the chest is tapped.
The blood shows an increase in number of white blood
cells and sedimentation rate (clumping of red blood cells).
Infarcts that do not heal within two or three days gener-
ally take two to three weeks to heal. The dead tissue is
replaced by scar tissue.
Cystic Fibrosis
Cystic fibrosis, also known as mucoviscidosis, is an inher-
ited metabolic disorder, the chief symptom of which is the
production of a thick, sticky mucus that clogs the respira-
tory tract and the gastrointestinal tract. Cystic fibrosis
was not recognized as a separate disease until 1938 and was
then classified as a childhood disease because mortality
among afflicted infants and children was high. However,
by the mid-1980s, more than half of all victims of cystic
fibrosis survived into adulthood owing to aggressive ther-
apeutic measures.
Cystic fibrosis is an inherited disorder mainly affect-
ing people of European ancestry. It is estimated to occur
in 1 per 2,000 live births in these populations and is par-
ticularly concentrated in people of northwestern European
descent. It is much less common among people of African
ancestry (about 1 per 17,000 live births) and is very rare in
people of Asian ancestry. The disorder was long known to
be recessive (i.e., only persons inheriting a defective gene
from both parents will manifest the disease). The disease
has no manifestations in heterozygotes (i.e., those indi-
viduals who have one normal copy and one defective copy
of the particular gene involved). However, when both
145
parents are heterozygous, they may expect that, on the

basis of chance, one out of four of their offspring will have
the disease. In 1989 the defective gene responsible for cys-
tic fibrosis was isolated. The gene, called cystic fibrosis
transmembrane conductance regulator, or CFTR, lies in
the middle of chromosome 7 and encodes a protein of the
same name, designated CFTR.
Cystic fibrosis affects the functioning of the body’s
exocrine glands (e.g., the mucus-secreting and sweat
glands) in the respiratory and digestive systems. Within
the cells of the lungs and gut, the CFTR protein trans-
ports chloride across cell membranes and regulates other
channels. These functions are critical for maintaining and
adjusting the fluidity of mucous secretions. Most cases of
cystic fibrosis are caused by a mutation that corresponds
to the production of a CFTR protein that lacks the amino
acid phenylalanine. As a result, chloride and sodium ions
accumulate within cells, thereby drawing fluid into the
cells and causing dehydration of the mucus that normally
coats these surfaces. The thick, sticky mucus accumulates
in the lungs, plugging the bronchi and making breathing
difficult. This results in chronic respiratory infections,
often with Staphylococcus aureus or Pseudomonas aeruginosa.
Chronic cough, recurrent pneumonia, and the progressive
loss of lung function are the major manifestations of lung
disease, which is the most common cause of death of per-
sons with cystic fibrosis.
In the digestive system, the abnormally thick mucous
secretions interfere with the passage of digestive enzymes
and thus block the body’s absorption of essential nutri-
ents. The resulting maldigestion and malabsorption of
food can cause affected individuals to become malnour-
ished despite an adequate diet. Bulky, greasy, foul-smelling
stools are often the first signs of cystic fibrosis. About 10
146
percent of infants with cystic fibrosis have intestinal

obstruction at birth due to very thick secretions. In addi-
tion, mutations in the CFTR gene are associated with
degeneration of the ductus deferens and sterility in adult
males who have cystic fibrosis.
Cystic fibrosis causes the sweat glands to produce
sweat that has an abnormally high salt content. The high
salt content in perspiration is the basis for the “sweat
test,” which is the definitive diagnostic test for the pres-
ence of cystic fibrosis. Mutations associated with cystic
fibrosis can be detected in screening tests. These tests are
effective in the identification of adult carriers (heterozy-
gotes), who may pass a mutation on to their offspring, as
well as in the identification of newborns who may be at
risk for the disorder.
The treatment of cystic fibrosis includes the intake of
pancreatic enzyme supplements and a diet high in calo-
ries, protein, and fat. Vigorous physical therapy on a daily
basis is used to loosen and drain the mucous secretions
that accumulate in the lungs. Medications such as dornase
alfa, a recombinant form of the enzyme deoxyribonucle-
ase, are given to thin mucus, facilitating its clearance from
the lungs through coughing. In addition, bronchodilators
can be used to relax the smooth muscles that line the air-
ways and cause airway constriction, making it easier for
patients to breathe. These agents may be administered by
means of an inhaler or a nebulizer, which is powered by a
compressor that sprays aerosolized drug into the airways.
The anti-inflammatory agent ibuprofen has been shown
to slow the deterioration of lung tissue in some cystic
fibrosis patients. In severe cases, lung transplantation may
be considered. Many patients with cystic fibrosis regularly
take antibiotics, sometimes in aerosolized form, in order
to fight lung infections.
147
Among the most promising treatments under inves-

tigation for cystic fibrosis is gene therapy. Gene therapy
first emerged as a potential form of treatment in 1990,
when researchers successfully restored CFTR chloride
channel function in cultured lung and airway epithelial
cells that carried CFTR mutations. The researchers
used recombinant DNA technology to generate viral
vectors containing normal copies of the CFTR gene.
These vectors were then transfected into the cultured
cells, which subsequently incorporated the normal
genes into their DNA. This success led to the first clini-
cal trial of gene therapy for cystic fibrosis in 1993. The
same technology was used to insert the CFTR gene into
a replication-deficient adenovirus that was then admin-
istered into the noses and lungs of patients. This first
trial initially appeared to be successful, since increased
expression of the CFTR protein was observed shortly
after treatment. However, the patients experienced
severe side effects, including lung inflammation and
signs of viral infection. Since the 1990s, gene therapy
for cystic fibrosis has undergone significant refine-
ment, and the outcomes of clinical trials are marked by
steady improvement. However, the natural defense sys-
tems of the lungs and airways have proved significant
obstacles to cellular uptake of the viral vector carrying
the normal CFTR gene. As a result, the development of
an effective gene delivery system has become a major
focus of cystic fibrosis gene therapy. Delivery systems
under investigation include cationic polymer vectors,
cationic liposomes, and adenovirus associated virus.
The latter, which can bind to a type of receptor
expressed in high numbers on the surfaces of lung cells,
has proved particularly effective in laboratory studies
using human lung tissue.
148
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis is also known as crypto-

genic fibrosing alveolitis. This is a generally fatal lung
disease of unknown cause that is characterized by pro-
gressive fibrosis of the alveolar walls. The disease most
commonly manifests between ages 50 and 70, with insidi-
ous onset of shortness of breath on exertion. A dry cough
is common as well. Sharp crackling sounds, called rales or
“Velcro crackles,” are heard through a stethoscope applied
to the back in the area of the lungs. Computerized tomog-
raphy (CT) imaging shows fibrosis and cysts that
characteristically form in a rim around the lower outer
portions of both lungs. In addition, pulmonary function
testing shows a reduction in lung volume. Lung biopsies
confirm the diagnosis by showing fibrosis with a lack of
inflammation.
The disease causes progressive shortness of breath
with exercise and ultimately produces breathlessness at
rest. Hypoxemia (decreased levels of oxygen in the blood)
initially occurs with exercise and later at rest and can be
severe. Some individuals have clubbed fingertips and toes.
The average duration of survival from diagnosis is four to
six years; however, some people live 10 years or longer.
Aside from administration of supplemental oxygen, there
is no effective treatment. Some individuals may benefit
from single or double lung transplantation.
Sarcoidosis and Eosinophilic Granuloma

Sarcoidosis is a disease of unknown cause characterized by
the development of small aggregations of cells, or granulo-
mas, in different organs; the lung is commonly involved.
Other common changes are enlargement of the lymph
149
glands at the root of the lung, skin changes, inflammation

in the eye, and liver dysfunction. Occasionally, nerve
sheaths are inflamed, leading to signs of involvement in
the affected area. The kidney is not commonly involved,
but some changes in blood calcium levels occur in a small
percentage of cases. In most cases the disease is first
detected on chest radiographs. Evidence of granulomas in
the lung may be visible, but often there is little interfer-
ence with lung function. The disease usually remits
without treatment within a year or so, but in a small pro-
portion of cases it progresses, leading finally to lung
fibrosis and respiratory failure. The granulomatous inflam-
mation in sarcoidosis can be controlled by long-term
administration of a corticosteroid such as prednisone.
Eosinophilic granuloma, also known as histiocytosis
X, is a disease associated with the excess production of
histiocytes, a subgroup of immune cells. It causes lesions
in lung tissue and sometimes also in bone tissue.
Eosinophilic granuloma is a lung condition that may spon-
taneously “burn out,” leaving the lung with some
permanent cystic changes. Although its cause is unknown,
the incidence is greatly increased in cigarette smokers.
Pulmonary Alveolar Proteinosis

Pulmonary alveolar proteinosis is a respiratory disorder
caused by the filling of large groups of alveoli with exces-
sive amounts of surfactant, a complex mixture of protein
and lipid (fat) molecules. The alveoli are air sacs, minute
structures in the lungs in which the exchange of respira-
tory gases occurs. The gas molecules must pass through a
cellular wall, the surface of which is generally covered by
a thin film of surfactant material secreted from the alveo-
lar cells. When too much surfactant is released from
the alveolar cells, or when the lung fails to remove the
150
surfactant, gas exchange is greatly hindered and the symp-

toms of alveolar proteinosis occur.
The disease manifests itself in laboured breathing at
rest or shortness of breath with exertion, and it is often
accompanied by chest pain and a dry cough. There may
also be general fatigue and weight loss. The skin becomes
tinged with blue in the most serious cases, an indication
that blood is not being adequately oxygenated or rid of
carbon dioxide. X-rays most frequently show evidence
of excess fluids in the lungs.
The precipitating cause of the disease is unknown.
Persons affected are usually between ages 20 and 50. The
disease can exist without causing symptoms for consider-
able periods, and spontaneous improvement has been
known to occur; it is sometimes fatal, but rarely so, if
treated. Treatment involves removal of the material by a
rinsing out of the lungs (lavage). One lung at a time is
rinsed with a saltwater solution introduced through the
windpipe. The fluids drawn back out of the lungs have
been found to have a high content of fat. Sometimes the
lesions totally clear up after one procedure, but subse-
quent treatments are often necessary.
Immunologic Conditions of the Lung

The lung is often affected by generalized diseases of the
blood vessels. Wegener granulomatosis, an acute inflam-
matory disease of the blood vessels believed to be of
immunologic origin, is an important cause of pulmonary
blood vessel inflammation. Acute hemorrhagic pneumo-
nitis occurring in the lung in association with changes in
the kidney is known as Goodpasture syndrome. The con-
dition has been successfully treated by exchange blood
transfusion, but its cause is not fully understood.
Pulmonary hemorrhage also occurs as part of a condition
151
known as pulmonary hemosiderosis, which results in the

accumulation of the iron-containing substance hemosid-
erin in the lung tissues.
The lung may also be involved in a variety of ways in the
disease known as systemic lupus erythematosus, which is
also believed to have an immunologic basis. Pleural effu-
sions may occur, and the lung parenchyma may be involved.
These conditions have only recently been recognized and
differentiated; accurate diagnosis has been much improved
by refinements in radiological methods, by the use of pul-
monary function tests, and especially by improvement in
thoracic surgical techniques and anesthesia that have made
lung biopsy much less dangerous than it formerly was.
The common condition of rheumatoid arthritis may
be associated with scattered zones of interstitial fibrosis
in the lung or with solitary isolated fibrotic lesions. More
rarely, a slowly obliterative disease of small airways (bron-
chiolitis) occurs, leading finally to respiratory failure.
Lung Cancer
Lung cancer is a disease characterized by uncontrolled
growth of cells in the lungs. Lung cancer was first described
by doctors in the mid-19th century. In the early 20th cen-
tury it was considered relatively rare, but by the end of the
century it was the leading cause of cancer-related death
among men in more than 25 developed countries. In the
21st century, lung cancer emerged as the leading cause of
cancer deaths worldwide, resulting in an estimated 1.3 mil-
lion deaths each year. In women, lung cancer is the second
leading cause of death from cancer globally, following
breast cancer. In the United States, however, it has sur-
passed breast cancer. The rapid increase in the worldwide
prevalence of lung cancer was attributed mostly to the
increased use of cigarettes following World War I.
152
Causes and Symptoms
Lung cancer occurs primarily in persons between ages 45

and 75. In countries with a prolonged history of cigarette
smoking, between 80 and 90 percent of all cases are caused
by smoking. Heavy smokers have a greater likelihood of
developing the disease than do light smokers. The risk is
also greater for those who started smoking at a young age.
Passive inhalation of cigarette smoke (sometimes
called secondhand smoke) is linked to lung cancer in
nonsmokers. According to the American Cancer Society,
secondhand smoke accounts for an estimated 3,400 deaths
from lung cancer in nonsmoking adults in the United
States each year. Other risk factors include exposure to
radon gas and asbestos; smokers exposed to these sub-
stances run a greater risk of developing lung cancer than
do nonsmokers. Uranium and pitchblende miners, chro-
mium and nickel refiners, welders, and workers exposed
to halogenated ethers also have an increased incidence, as
do some workers in hydrocarbon-related processing, such
as coal processors, tar refiners, and roofers. Lung cancer is
rarely caused directly by inherited mutations.
Tumours can begin anywhere in the lung, but symp-
toms do not usually appear until the disease has reached
an advanced stage or spread to another part of the body.
The most common symptoms include shortness of breath,
a persistent cough or wheeze, chest pain, bloody sputum,
unexplained weight loss, and susceptibility to lower respi-
ratory infections. In cases where the cancer has spread
beyond the lungs, visible lumps, jaundice, or bone pain
may occur.
Types of Lung Cancer

Once diagnosed, the tumour’s type and degree of invasive-
ness are determined. Of the two basic forms, small-cell
153
carcinoma accounts for 20 to 25 percent of all cases and

non-small-cell carcinoma is responsible for the remainder.
Small-cell carcinoma (SCLC), also called oat-cell carci-
noma, is rarely found in people who have never smoked. It
is characterized by cells that are small and round, oval, or
shaped like oat grains. SCLC is the most aggressive type
of lung cancer. Because it tends to spread quickly before
symptoms become apparent, the survival rate is very low.
Non-SCLCs consist primarily of three types of tumour:
squamous cell carcinoma, adenocarcinoma, and large-cell
carcinoma. Adenocarcinoma accounts for some 25 to 30
percent of cases worldwide, but it is the most common type
of lung cancer in the United States. Cells of adenocarci-
noma are cube- or column-shaped, and they form structures
that resemble glands and are sometimes hollow. Tumours
often originate in the smaller, peripheral bronchi. Symptoms
at the time of diagnosis often reflect invasion of the lymph
nodes, pleura, and both lungs or metastasis to other organs.
Some 25 to 30 percent of primary lung cancers are squa-
mous cell carcinomas, also called epidermoid carcinomas.
This tumour is characterized by flat, scalelike cells, and it
often develops in the larger bronchi of the central portion
of the lungs. Squamous cell carcinoma tends to remain
localized longer than other types and thus is generally
more responsive to treatment.
About 10 percent of all lung cancers are large-cell car-
cinomas. There is some dispute as to whether these
constitute a distinct type of cancer or are merely a group
of unusual squamous cell carcinomas and adenocarcino-
mas. Large-cell carcinomas can begin in any part of the
lung and tend to grow very quickly.
Diagnosis, Treatment, and Prevention

Lung cancers are often discovered during examinations for
other conditions. Cancer cells may be detected in sputum;
154
a needle biopsy may be used to remove a sample of lung

tissue for analysis; or the large airways of the lungs (bron-
chi) can be viewed directly with a bronchoscope for signs
of cancer. Noninvasive methods include X-rays, computed
tomography (CT) scans, positron emission tomography
(PET) scans, and magnetic resonance imaging (MRI).
There are also several blood tests that may be used to
detect proteins and other substances known to be associ-
ated with lung cancer. For example, abnormal fluctuations
in the serum levels of parathormone or the presence in the
blood of a protein called cytokeratin 19 fragment or of sub-
stances known as carcinogenic antigens may be indicative
of malignant lung disease. Most cases are usually diagnosed
well after the disease has spread (metastasized) from its
original site. For this reason, lung cancer has a poorer prog-
nosis than many other cancers. Even when it is detected
early, the five-year survival rate is about 50 percent.
As with most cancers, treatments for lung cancer
include surgery, chemotherapy, and radiation. The choice
of treatment depends on the patient’s general health, the
stage or extent of the disease, and the type of cancer. The
type of treatment an individual patient receives may also
be based on the results of genetic screening, which can
identify mutations that render some lung cancers suscep-
tible to specific drugs.
Surgery involves the removal of a cancerous segment
(segmentectomy), a lobe of the lung (lobectomy), or the
entire lung (pneumonectomy). Lung surgery is serious and
can lead to complications such as pneumonia or bleeding.
Although removal of an entire lung does not prohibit oth-
erwise healthy people from ultimately resuming normal
activity, the already poor condition of many patients’ lungs
results in long-term difficulty in breathing after surgery.
Radiation may be used alone or in conjunction with
surgery—either before surgery to shrink tumours or
155
following surgery to destroy small amounts of cancerous

tissue. Radiation treatment may be administered as exter-
nal beams or surgically implanted radioactive pellets
(brachytherapy). Side effects include vomiting, diarrhea,
fatigue, or additional damage to the lungs. Chemotherapy
uses chemicals to destroy cancerous cells, but these chem-
icals also attack normal cells to varying degrees, causing
side effects that are similar to radiation therapy. An exper-
imental technology that has shown promise in the
treatment of lung cancer is microwave ablation, which
relies on heat derived from microwave energy to kill can-
cer cells. Early studies in small subsets of patients have
demonstrated that microwave ablation can shrink and
possibly even eliminate some lung tumours.
The probability of developing lung cancer can be
greatly reduced by avoiding smoking. Smokers who quit
also reduce their risk significantly. Testing for radon gas
and avoiding exposure to coal products, asbestos, and
other airborne carcinogens also lowers risk.
Diseases of the mediastinum

and diaphragm
The mediastinum comprises the fibrous membrane in the
centre of the thoracic cavity, together with the many
important structures situated within it. Enlargement of
lymph glands in this region is common, particularly in the
presence of lung tumours or as part of a generalized
enlargement of lymphatic tissue in disease. Primary
tumours of mediastinal structures may arise from the thy-
mus gland or the lower part of the thyroid gland;
noninvasive cysts of different kinds are also found in the
mediastinum.
Mediastinal emphysema occurs when a pocket of air
forms within the mediastinum and thus surrounds the
156
heart and central blood vessels. This usually occurs as a

result of lung rupture. When the alveoli of the lungs rupture
because of traumatic injury or lung disease, the released air
seeks an area of escape. One pathway that the air can fol-
low is through the lung tissue into the mediastinum, where
accumulating air can cause sufficient pressure to impair
normal heart expansion and blood circulation.
Mediastinal emphysema is one of the maladies that
can afflict underwater divers who breathe compressed air.
As a diver descends, the external pressure upon his or her
body increases. The air the diver breathes is more dense
and concentrated than the air breathed on the surface.
While the diver remains deeply submerged, there is no
difficulty; when he or she begins to ascend again, however,
the external pressure decreases, and the lungs begin to
expand because the air inside has less pressure to contain
it. If the diver breathes normally or exhales as he or she
ascends at a moderate rate, the extra gas pressure is
relieved by exhaling. If the diver holds his or her breath,
rises too rapidly, or has respiratory obstructions such as
cysts, mucus plugs, or scar tissue, which do not permit suf-
ficient release of air, the lungs become overinflated and
rupture. Air bubbles can then enter the veins and capillar-
ies of the circulatory system directly, causing an air
embolism, or they can travel through the lung tissue to
other areas of the body.
In mediastinal emphysema the air bubbles usually pass
along the outside of blood vessels and the bronchi until
they reach the mediastinal cavity. This area contains the
heart, major blood vessels, main bronchi, and the trachea.
Air trapped in the mediastinum expands as the diver con-
tinues to rise. The pressure may cause intense pain beneath
the rib cage and in the shoulders; the expanding air may
compress the respiratory passageways, making breathing
difficult, and collapse blood vessels vital to circulation.
157
The symptoms of mediastinal emphysema may range from

pain under the breastbone, shock, and shallow breathing
to unconsciousness, respiratory failure, and cyanosis (blue
colouring of the skin). In cases in which the symptoms are
not severe, the air will be absorbed by the body, or it may
be removed by inserting a long hypodermic needle into
the mediastinum to draw off the air. If there is respiratory
or circulatory distress, the victim must be recompressed
in a hyperbaric chamber so that the body can resume its
essential functions before the air is removed.
Diseases and disorders that affect the diaphragm can
cause fundamental changes in respiratory function. For
example, bilateral diaphragmatic paralysis can lead to a
severe reduction in vital capacity, especially when the sub-
ject is recumbent (lying down). In many cases the cause of
the paralysis cannot be determined. Paralysis of the dia-
phragm on one side is more common and better tolerated
than bilateral paralysis, although some shortness of breath
on exertion is often present. The function of the dia-
phragm may be compromised when the lung is highly
overinflated, as occurs in emphysema; diaphragmatic
fatigue may limit the exercise capability of affected per-
sons. In some persons the diaphragm may be incompletely
formed at birth; this can lead to herniation of the abdomi-
nal viscera through the diaphragm.
158
CHAPTER6
ALLERGIC AND OCCUPATIONAL
LUNG DISEASES AND ACUTE
RESPIRATORY CONDITIONS
A llergic and occupational lung diseases comprise
two groups of conditions that are associated with
the exposure to and inhalation of particulate matter. In the
case of allergies, affected persons are highly sensitive to
substances such as dust or pollen. In occupational disease,
however, exposure to harmful irritants, such as asbestos
and coal dust, causes respiratory disease in otherwise
healthy workers. For most affected persons, reducing
exposure to the irritant relieves the symptoms of their
condition. In some cases of occupational exposure, severe
respiratory disease may ensue, leading to cancer and sub-
stantial loss of lung function.
Respiratory function can be severely compromised by
a variety of other conditions, many of which are acute in
nature. For example, traumatic conditions, such as respi-
ratory distress syndrome, require immediate medical
administration of oxygen and ultimately mechanical ven-
tilation in order to prevent lung collapse and death.
Carbon monoxide poisoning, altitude sickness, decom-
pression sickness, and drowning are other examples of
acute conditions that can result in respiratory failure.
allergic lung diseases

There are at least three reasons why the lungs are particu-
larly liable to be involved in allergic responses. First, the
lungs are exposed to the outside environment, and, hence,
159
particles of foreign substances such as pollen may be

deposited directly in the lungs; second, the walls of the
bronchial tree contain smooth muscle that is very likely to
be stimulated to contract if histamine is released by cells
affected by the allergic reaction; and, third, the lung con-
tains a very large vascular bed, which may be involved in
any general inflammatory response. It is therefore not sur-
prising to find that sensitivity phenomena are common
and represent an important aspect of pulmonary disease
as a whole. The most common and most important of
these is asthma.
Asthma
Asthma is a chronic disorder of the lungs in which inflamed
airways are prone to constrict, causing episodes of wheez-
ing, chest tightness, coughing, and breathlessness that
range in severity from mild to life-threatening. Asthmatic
episodes may begin suddenly or may take days to develop.
Although an initial episode can occur at any age, approxi-
mately half of all cases occur in persons younger than age
10, boys being affected more often than girls. Among
adults, however, women are affected more often than men.
When asthma develops in childhood, it is often
associated with an inherited susceptibility to allergens—
substances, such as pollen, dust mites, or animal dander,
that may induce an allergic reaction. In adults, asthma may
develop in response to allergens, but viral infections, aspi-
rin, weather conditions, and exercise may cause it as well. In
addition, stress may exacerbate symptoms. Adults who
develop asthma may also have chronic rhinitis, nasal pol-
yps, or sinusitis. Adult asthma is sometimes linked to
exposure to certain materials in the workplace, such as
chemicals, wood dusts, and grains. These substances pro-
voke both allergic and nonallergic forms of the disease. In
160
7 Allergic and Occupational Lung Diseases and Acute Respiratory Conditions 7
During normal breathing, inhaled air travels through two main channels
(primary bronchi) that branch within each lung into smaller, narrower pas-
sages (bronchioles) and finally into the tiny, terminal bronchial tubes. During
an asthma attack, smooth muscles that surround the airways spasm, which
results in tightening of the airways; swelling and inflammation of the inner
airway space (lumen) cause fluid buildup and infiltration by immune cells and
excessive secretion of mucus into the airways. Consequently, air is obstructed
from circulating freely in the lungs and cannot be expired. Encyclopædia
Britannica, Inc.
most of these cases, symptoms will subside if the causative

agent is removed from the workplace.
Asthma is classified based on the degree of symptom
severity, which can be divided into four categories: mild
intermittent, mild persistent, moderate persistent, and
severe persistent. Although the mechanisms underlying
an asthmatic episode are not fully understood, in general
161
it is known that exposure to an inciting factor stimulates

the release of chemicals from the immune system. These
chemicals can cause spasmodic contraction of the smooth
muscle surrounding the bronchi, swelling and inflamma-
tion of the bronchial tubes, and excessive secretion of
mucus into the airways. The inflamed, mucus-clogged air-
ways act as a one-way valve (i.e., air is inspired but cannot
be expired). The obstruction of airflow may resolve spon-
taneously or with treatment.
A number of medications are used to prevent and con-
trol the symptoms of asthma and to reduce the frequency
and severity of episodes. Asthma medications are catego-
rized into three main types: anti-inflammatory agents,
which suppress inflammation; bronchodilators, which
relax smooth muscle constriction and open the airways;
and leukotriene modifiers, which interrupt the chemi-
cal signaling within the body that leads to constriction
and inflammation. These medications may be taken on a
long-term daily basis to maintain and control persistent
asthma (long-term control medications), or they may be
used to provide rapid relief from constriction of airways
(quick-relief medications). Long-term control medica-
tions include corticosteroids, which are the most potent
and effective anti-inflammatory medications available;
cromolyn sodium and nedocromil, which are anti-inflam-
matory medications often prescribed for children;
long-acting beta2-agonists and methylxanthines (e.g., the-
ophylline), which are bronchodilators; and zileuton and
zafirlukast, which are leukotriene modifiers. Quick-relief
medications may include bronchodilators, such as short-
acting beta2-agonists and ipratropium bromide, or systemic
corticosteroids. Agents that block enzymes called phos-
phodiesterases, which are involved in mediating airway
constriction and inflammation, are in clinical trials. These
162
drugs are designed to be long-lasting—administered once

per day via inhalation—and are expected to be safer than
traditional medications, which may cause cardiovascular
damage. A prolonged asthma attack that does not respond
to medication is called status asthmaticus. A person with
this condition must be hospitalized to receive oxygen and
other treatment.
In addition to managing asthma with medications,
persons who suffer from the disease are advised to mini-
mize their exposure to the substances that trigger asthma.
The ability to recognize the early warning signs of an
impending episode is important, and individuals can mon-
itor the level of airflow obstruction in their lungs by using
a pocket-size device called a peak flow meter.
In developed countries and especially in urban areas,
the number of asthma cases has increased steadily. Today
asthma affects more than 7 percent of children and about
9 percent of adults. Reasons for this dramatic surge in
asthma cases, particularly among children, are not
entirely clear. Air pollution, crowded living conditions,
smoking, exposure to secondhand smoke, and even cock-
roaches have been blamed for the increase. However, in
many underdeveloped tropical regions of the world, very
few people are affected by allergies or asthma. In those
areas, millions of people are infected with Necator ameri-
canus, a species of hookworm. Studies have shown that
hookworms reduce the risk of asthma by decreasing the
activity of the human host’s immune system. In 2006 a
clinical trial conducted in a small number of patients
demonstrated that deliberate infection with 10 hook-
worm larvae, too few to cause hookworm disease, can
relieve symptoms of allergy and asthma. Further investi-
gation of this “helminthic therapy” in larger sample
populations is under way.
163
There has been some controversy concerning increased

rates of asthma in countries where childhood vaccination
is widespread. Although not yet successfully confirmed,
studies have indicated that only one vaccine, pertussis
vaccine, may give rise to asthma. In a reverse scenario,
protection against asthma conferred by BCG vaccination
(for defense against tuberculosis) has been proved only in
children with a history of allergic rhinitis (hay fever).
Antibiotics may also interfere with immune development.
Children who are given broad-spectrum antibiotics (effec-
tive against multiple microorganisms) before two years of
age are three times more likely to develop asthma than are
children who are not given such antibiotics.
Hay Fever
Hay fever, also known as allergic rhinitis, is a common sea-
sonal condition caused by allergy to grasses and pollens.
Seasonally recurrent bouts of sneezing, nasal congestion,
and tearing and itching of the eyes caused by allergy to the
pollen of certain plants, chiefly those depending upon the
wind for cross-fertilization, such as ragweed in North
America and timothy grass in Great Britain.
In allergic persons contact with pollen releases hista-
mine from the tissues, which irritates the small blood
vessels and mucus-secreting glands. Symptoms may be
aggravated by emotional factors. Antihistamine drugs and
inhaled corticosteroids provide symptomatic relief. The
most effective long-term treatment is immunotherapy,
desensitization by injections of an extract of the causative
pollen administered once or twice a week for one or more
years. Hay fever, like other allergic diseases, shows a famil-
ial tendency and may be associated with other allergic
disorders, such as dermatitis or asthma.
164
Giant ragweed (Ambrosia trifida) is a common cause of hay fever. Ragweed

pollen is typically dispersed in the air from late summer to mid-fall in many
areas of central and eastern North America. Louise K. Broman—Root
Resources
165
Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis is an important group of

conditions in which the lung is sensitized by contact with
a variety of agents and in which the response to reexpo-
sure consists of an acute pneumonitis, with inflammation
of the smaller bronchioles, alveolar wall edema, and a
greater or lesser degree of airflow obstruction due to
smooth muscle contraction. In more chronic forms of the
condition, granulomas, or aggregations of giant cells, may
be found in the lung. Inflammation can lead to widespread
lung fibrosis and chronic respiratory impairment.
One of these illnesses is the so-called farmer’s lung,
caused by the inhalation of spores from moldy hay (ther-
mophilic Actinomyces). This causes an acute febrile illness
with a characteristically fine opacification (clouding, or
becoming opaque) in the basal regions of the lung on the
chest radiograph. Airflow obstruction in small airways is
present, and there may be measurable interference with
diffusion of gases across the alveolar wall. If untreated, the
condition may become chronic, with shortness of breath
persisting after the radiographic changes have disap-
peared. Farmer’s lung is common in Wisconsin, on the
eastern seaboard of Canada, in the west of England, and
in France. Education of farmers and their families and
the wearing of a simple mask can completely prevent the
condition.
A similar group of diseases occurs in those with close
contact with birds. Variously known as pigeon breeder’s
lung or bird fancier’s lung, these represent different kinds
of allergic responses to proteins from birds, particularly
proteins contained in the excreta of pigeons, budgerigars
(parakeets), and canaries. An acute hypersensitivity pneu-
monitis may also occur in those cultivating mushrooms
(particularly where this is done below ground), after
166
Some species of the fungi genus Aspergillus can cause allergic reactions and
mild pneumonia in susceptible individuals. Runk/Schoenberger from
Grant Heilman
exposure to redwood sawdust, or in response to a variety

of other agents. An influenza-like illness resulting from
exposure to molds growing in humidifier systems in office
buildings (“humidifier fever”) has been well documented.
It is occasionally attributable to Aspergillus, but sometimes
the precise agent cannot be identified. The disease may
present as an atypical nonbacterial pneumonia and may be
labeled a viral pneumonia if careful inquiry about possible
contacts with known agents is not made.
occupational lung disease

Occupational lung diseases are caused by the inhalation
of a variety of organic or inorganic dusts or chemical
167
irritants, usually over a prolonged period of time. The lung

diseases that result from the inhalation of such irritants
are known medically as pneumoconioses. The type and
severity of disease depends on the composition of the
dust; small quantities of some substances, notably silica
and asbestos, produce grave reactions, while milder irri-
tants produce symptoms of lung disease only with massive
exposure. Much evidence indicates that the smoking of
cigarettes in particular aggravates the symptoms of many
of the pneumoconiosis diseases.
Typically, the early symptoms of mild pneumoconioses
include chest tightness, shortness of breath, and cough,
progressing to more serious breathing impairment,
chronic bronchitis, and emphysema in the most severe
cases. Inhaled dust collects in the alveoli, or air sacs, of the
lung, causing an inflammatory reaction that converts nor-
mal lung tissue to fibrous scar tissue and thus reduces the
elasticity of the lung. If enough scar tissue forms, lung
function is seriously impaired, and the clinical symptoms
of pneumoconiosis are manifested. The total dust load in
the lung, the toxic effects of certain types of dust, and
infections of the already damaged lung can accelerate the
disease process.
Among inorganic dusts, silica, encountered in numer-
ous occupations, is the most common cause of severe
pneumoconiosis. As little as 5 or 6 grams (about 0.2
ounce) in the lung can produce disease. Graphite, tin,
barium, chromate, clay, iron, and coal dusts are other
inorganic substances known to produce pneumoconiosis,
although silica exposure is also involved in many cases.
Pneumoconioses associated with these substances usually
result only from continued exposure over long periods.
Asbestos, beryllium, and aluminum dusts can cause a
more severe pneumoconiosis, often after relatively brief
168
exposure to massive amounts of dust. Asbestosis has also

been associated with cancers of the lung and other organs.
Prolonged exposure to organic dusts such as spores
of molds from hay, malt, sugarcane, mushrooms, and
barley can produce lung disease through a severe allergic
response within a few hours of exposure, even in previ-
ously nonallergic persons. Brown lung disease in textile
workers is also a form of pneumoconiosis, caused by fibres
of cotton, flax, or hemp that, when inhaled, stimulate
histamine release. Histamines cause the air passages to
constrict, impeding exhalation.
Chemical irritants that have been implicated in lung
disease include sulfur dioxide, nitrogen dioxide, ammonia,
acid, and chloride, which are quickly absorbed by the lining
of the lungs. The chemicals themselves may scar the deli-
cate lung tissues, and their irritant effect may cause large
amounts of fluid to accumulate in the lungs. Once exposure
to the chemical ceases, the patient may recover completely
or may suffer from chronic bronchitis or asthma.
Silicosis
Silicosis is a chronic disease of the lungs that is caused by
the inhalation of silica dust over long periods of time.
(Silica is the chief mineral constituent of sand and of many
kinds of rock.) The disease occurs most commonly in min-
ers, quarry workers, stonecutters, tunnelers, and workers
whose jobs involve grinding, sandblasting, polishing, and
buffing. Silicosis is one of the oldest industrial diseases,
having been recognized in knife grinders and potters in
the 18th century, and it remains one of the most common
dust-induced respiratory diseases in the developed world.
In most instances, 10 to 20 years of occupational expo-
sure to silica dust are needed for silicosis to develop. The
169
disease rarely occurs with exposures to concentrations of

less than 6,000,000 particles of silica per cubic foot
(about 210,000 per litre) of air. Only very small silica par-
ticles less than 10 microns (0.0004 inch) in diameter
penetrate to the finer air passages of the lungs, and parti-
cles of one to three microns do the most damage.
The symptoms of silicosis are shortness of breath that
is followed by coughing, difficulty in breathing, and weak-
ness. These symptoms are all related to a fibrosis that
reduces the elasticity of the lung. In the actual disease
process, the tiny particles of inhaled silica are taken up in
the lungs by scavenger cells, called macrophages, that
serve to protect the body from bacterial invasion. Silica
particles, however, cannot be digested by the macrophages
and instead kill them. The killed cells accumulate and
form nodules of fibrous tissue that gradually enlarge
to form fibrotic masses. These whorls of fibrous tissue
may spread to involve the area around the heart, the open-
ings to the lungs, and the abdominal lymph nodes. Lung
volume is reduced, and gas exchange is poor. Silicosis pre-
disposes a person to tuberculosis, emphysema, and
pneumonia. In the past a large proportion of sufferers of
silicosis died of tuberculosis, though this has changed with
the availability of drug therapies for that disease.
There is no cure for silicosis, and, since there is no
effective treatment, control of the disease lies mainly in
prevention. The use of protective face masks and proper
ventilation in the workplace and periodic X-ray monitor-
ing of workers’ lungs has helped lessen the incidence of
the disease.
Black Lung
Black lung, also known as coal-worker’s pneumoconiosis,
is a respiratory disorder caused by repeated inhalation of
170
coal dust over a period of years. The disease gets its name
from a distinctive blue-black marbling of the lung caused
by accumulation of the dust. Georgius Agricola, a
German mineralogist, first described lung disease in coal
miners in the 16th century, and it is now widely recog-
nized. It may be the best known occupational illness in
the United States.
The disease is most commonly found among miners of
hard coal, but it also occurs in soft-coal miners and graph-
ite workers. Onset of the disease is gradual. Symptoms
usually appear only after 10 to 20 years of exposure to coal
dust, and the extent of disease is clearly related to the total
dust exposure. It is not clear, however, whether coal itself
is solely responsible for the disease, as coal dust often is
contaminated with silica, which causes similar symptoms.
There is strong evidence that tobacco smoking aggravates
the condition. The early stages of the disease (when it is
called anthracosis) usually have no symptoms, but in its
more advanced form it frequently is associated with pul-
monary emphysema or chronic bronchitis and can be
disabling; tuberculosis is also more common in victims of
black lung.
Asbestosis and Mesothelioma

The widespread use of asbestos as an insulating material
during World War II, and later in flooring, ceiling tiles,
brake linings, and as a fire protectant sprayed inside
buildings, led to a virtual epidemic of asbestos-related
disease 20 years later. The first disease recognized to be
caused by asbestos was asbestosis, which produces char-
acteristic changes in the lungs that can be identified in
chest X-rays and that can impair lung function at an early
stage. Later it was discovered that exposure to much
less asbestos than was needed to cause asbestosis led to
171
thickening of the pleura, and, when both cigarette smok-

ing and asbestos exposure occurred, there was a major
increase in the risk for lung cancer. The risks from
smoking and from significant asbestos exposure are mul-
tiplicative in the case of lung cancer. A malignant tumour
of the pleura known as mesothelioma is caused almost
exclusively by inhaled asbestos. Often a period of 20 years
or more elapses between exposure to asbestos and the
development of a tumour.
As far as is known, all the respiratory changes associ-
ated with asbestos exposure are irreversible. Malignant
mesothelioma is rare and unrelated to cigarette smoking,
but survival after diagnosis is less than two years. In most
cases, thickening of the pleura is not associated with dis-
turbance of lung function or with symptoms of exposure
to asbestos, although in occasional cases pleuritis is very
aggressive and thus may produce symptoms. It is not yet
understood exactly why asbestos devastates the tissues
of the lungs. Asbestos has been suspected to play a role
in stimulating certain cellular events, such as the genera-
tion of harmful reactive molecules and the activation of
damaging inflammatory processes. These events could
contribute to the scarring and fibrosis that are character-
istic of inhalation of asbestos fibres.
Not all types of asbestos are equally dangerous. The
risk of mesothelioma in particular appears to be much
higher if crocidolite, a blue asbestos that comes from
South Africa, is inhaled than if chrysotile is inhaled. But
exposure to any type of asbestos is believed to increase the
risk of lung cancer, especially when associated with ciga-
rette smoking. While the removal of asbestos from
buildings has greatly alleviated the risk of exposure to
asbestos for many people, inhalation of asbestos remains a
significant risk for the workers removing the material. All
172
industrialized countries have imposed strict regulations

for handling asbestos, and the workforce is generally aware
of the material’s dangers.
There is no curative therapy for asbestosis or meso-
thelioma. Treatment is aimed at managing symptoms,
preventing infections, and delaying disease progression.
Individuals with asbestosis often receive annual vaccina-
tions against influenza and pneumococcal pneumonia.
In some cases, aerosol medications that thin mucous
secretions and oxygen that is supplied by a portable tank
are necessary to maintain adequate oxygen intake. In
other cases, lung transplantation is required. Individuals
with mesothelioma often undergo chemotherapy and
radiation therapy, which may prolong survival for a short
period of time.
Respiratory Toxicity of Glass and

Metal Fibres
The increasing use of human-made mineral fibres (as in
fibreglass and rock wool) has led to concern that these
may also be dangerous when inhaled. Present evidence
suggests that they do increase the risk of lung cancer in
persons occupationally exposed to them. Standards for
maximal exposure have been proposed.
The toxicity of beryllium, known as berylliosis, was
first discovered when it was widely used in the manufac-
ture of fluorescent light tubes shortly after World War II.
Although beryllium is no longer used in the fluorescent
light industry, it is still important in the manufacture of
metal alloys and ceramics. Berylliosis involves the lungs
but occasionally affects only the skin. There are two forms:
an acute illness occurring most frequently in workers
extracting beryllium metal from ore or manufacturing
173
beryllium alloys, and a slow-developing chronic disease

occurring in scientific and industrial workers who are
exposed to beryllium-containing fumes and dust.
The acute disease involves both skin and lungs, caus-
ing a burning rash, eye irritation, nasal discharge, a cough,
and chest tightness. The skin disease is caused by direct
contact with beryllium salts and the lung disease by inha-
lation of metal dust or beryllium compounds. Most of
those affected by acute berylliosis recover within a few
months, but a small number of patients develop a highly
fatal inflammation of the lung within 72 hours after a brief,
massive exposure to beryllium. The chronic disease may
occur more than 15 years after exposure, although the later
it develops, the milder it is likely to be. It generally causes
shortness of breath, especially after exercise, exhaustion,
and a dry cough and can produce a permanent, though
moderate, disability.
Byssinosis
Byssinosis, or brown lung, is a respiratory disorder
caused by inhalation of an endotoxin produced by bacte-
ria in the fibres of cotton, flax, hemp, and other textiles.
Byssinosis is common among textile workers, who often
inhale significant amounts of cotton dust. Cotton dust
may stimulate inflammation that damages the normal
structure of the lung and causes the release of histamine,
which constricts the air passages. As a result, breathing
becomes difficult. Over time the dust accumulates in the
lung, producing a typical discoloration that gives the dis-
ease its common name.
Byssinosis was first recognized in the 17th century
and was widely known in Europe and England by the early
19th century. Today it is seen in most cotton-producing
174
regions of the world. Several years of exposure to cotton

dust are needed before byssinosis develops, and workers
with lower grade disease usually recover completely
upon leaving the industry or moving into an area with
less dust. Persons with mild byssinosis have a “Monday
feeling” of chest tightness and shortness of breath on the
first day of work after a weekend or holiday. As exposure
continues, this feeling persists throughout the week, and
in advanced stages, byssinosis causes chronic, irrevers-
ible obstructive lung disease. Because cotton is by far the
most common cause of byssinosis, this form of the con-
dition has been variably known as cotton-dust asthma
and cotton-mill fever.
Respiratory Toxicity of Industrial Chemicals

Toluene diisocyanate, used in the manufacture of polyure-
thane foam, may cause occupational asthma in susceptible
individuals at very low concentrations. In higher concen-
trations, such as may occur with accidental spillage, it
causes a transient flulike illness associated with airflow
obstruction. Prompt recognition of this syndrome has led
to modifications in the industrial process involved.
Although the acute effects of exposure to many of
these gases and vapours are well documented, there is less
certainty about the long-term effects of repeated low-level
exposures over a long period of time. This is particularly
the case when the question of whether work in a generally
dusty environment has contributed to the development of
chronic bronchitis or later emphysema. In other words,
whether such nonspecific exposures increase the risk of
these diseases in cigarette smokers.
Many chemicals can damage the lung in high concen-
tration: these include oxides of nitrogen, ammonia,
175
chlorine, oxides of sulfur, ozone, gasoline vapour, and ben-

zene. In industrial accidents, such as occurred in 1985 in
Bhopal, India, and in 1976 in Seveso, near Milan, people
in the neighbourhood of chemical plants were acutely
exposed to lethal concentrations of these or other chemi-
cals. The custom of transporting dangerous chemicals by
rail or road has led to the occasional exposure of bystand-
ers to toxic concentrations of gases and fumes. Although
in many cases recovery may be complete, it seems clear
that long-term damage may occur.
Disability and Attribution of

Occupational Lung Diseases
Occupational lung diseases are of social and legal impor-
tance. In such cases, respiratory specialists must assess
the extent of an individual’s disability and then form
an opinion on whether an individual’s disability can be
attributed to an occupational hazard. Pulmonary func-
tion testing and tests of exercise capability provide a
good indication of the impact of a disease on the physical
ability of a patient. However, it is much more difficult to
decide how much of a patient’s disability is attributable
to occupational exposure. If the exposure is historically
known to cause a specific lesion in a significant percent-
age of exposed persons, such as mesothelioma in workers
exposed to asbestos, attribution may be fairly straight-
forward. In many cases, however, the exposure may cause
only generalized pulmonary changes or lung lesions for
which the precise cause cannot be determined. These
instances may be complicated by a history of cigarette
smoking. Physicians asked to present opinions on attrib-
utability before a legal body frequently must rely on the
application of probability statistics to the individual case,
a not wholly satisfactory procedure.
176
Other respiratory conditions

Other respiratory conditions, ranging from poor pulmo-
nary circulation to carbon monoxide poisoning, comprise
a diverse group of diseases and disorders. The causative
factors of these conditions may include accidents, toxic
gases, environmental pollutants, and metabolic disorders.
In addition, conditions arising from exposure to extremes
in atmospheric pressure, which occurs during mountain
climbing and diving, account for an important set of
illnesses that can contribute to severe respiratory dysfunc-
tion in persons of otherwise exceptional health.
Circulatory Disorders
The lung is commonly involved in disorders of the circula-
tion. The most important and common of these is
blockage of a branch of the pulmonary artery by blood
clot, which has usually formed in the veins of the legs or of
the pelvis. The resulting pulmonary embolism leads to
changes in the lung supplied by the affected artery. When
severe, these changes are known as a pulmonary infarc-
tion. The consequences of embolism range from sudden
death, when the infarction is massive, to an increased
respiratory rate, slight fever, and occasionally some pleu-
ritic pain over the site of the infarction.
An individual is at an increased risk for pulmonary
embolism whenever his or her circulation is sluggish.
This occurs most often during a postoperative period
when the affected individual is immobilized in bed. Early
mobilization after surgery or childbirth is considered an
important preventive measure. Repetitive pulmonary
emboli may lead to chronic pulmonary thromboembo-
lism, in which the pressure in the main pulmonary artery
is persistently increased. Over time, a clot is replaced with
177
an adherent fibrous material in the pulmonary arteries,

causing shortness of breath on exertion and, ultimately,
right ventricular heart failure. The obstructing lesions
can be surgically removed in some instances, thereby
relieving symptoms of breathlessness.
In primary pulmonary hypertension, a condition of
unknown origin, a marked increase in pulmonary arterial
pressure occurs as a result of progressive narrowing and
obliteration of small pulmonary arteries. Primary pulmo-
nary hypertension leads to enlargement of the heart and
eventual failure of the right ventricle of the heart, usually
after increasing disability with severe shortness of breath.
In addition to chest X-rays and basic pulmonary function
tests, a diagnosis of pulmonary hypertension is often con-
firmed following an electrocardiogram (EKG) to assess
electrical function of the heart, an echocardiogram to
determine whether the heart is enlarged and to evaluate
the flow of blood through the heart, and cardiac catheter-
ization to measure pressure in the pulmonary artery and
right ventricle of the heart.
Treatment of primary pulmonary hypertension is
aimed at alleviating symptoms. Because of the variability
in physiological response to certain drugs and because of
the progressive nature of the disease, affected individuals
require careful, long-term evaluation and treatment.
While some medications such as calcium channel block-
ers may be taken orally, others such as prostacyclin are
given by continuous intravenous infusion supplied through
a portable battery-powered pump. Prostacyclin can some-
times be given in oral or inhaled forms. In some cases, lung
transplantation is necessary.
Congestion of the lungs (pulmonary edema) and the
development of fluid in the pleural cavity, with consequent
shortness of breath, follows left ventricular failure, usually
as a consequence of coronary arterial disease. When the
178
valve between the left atrium of the heart and the left ven-
tricle is thickened and deformed by rheumatic fever
(mitral stenosis), chronic changes develop in the lung as a
result of the increased pressure in the pulmonary circula-
tion. These changes contribute to the shortness of breath
and account for the blood staining of the sputum.
Respiratory Distress Syndrome

Respiratory distress syndrome is a condition that can
affect infants or adults. In infants it is also called hya-
line membrane disease. This complication is especially
common in premature newborns. It is characterized by
extremely laboured breathing, cyanosis (a bluish tinge
to the skin or mucous membranes), and abnormally low
levels of oxygen in the arterial blood. Before the advent
of effective treatment, respiratory distress syndrome of
infants was frequently fatal. Autopsies of children who
had succumbed to the disorder revealed that the air sacs
(alveoli) in their lungs had collapsed and a “glassy” (hya-
line) membrane had developed in the alveolar ducts.
Although respiratory distress syndrome occurs mostly
in premature, low-birth-weight infants (those weighing
less than 2.5 kg, or approximately 5.5 pounds), it also some-
times develops in full-term infants, particularly those born
to diabetic mothers. The disorder arises because of a lack
of surfactant, a pulmonary substance that prevents the
alveoli from collapsing after the infant’s first breaths have
been taken. The syndrome was formerly the leading cause
of death in premature infants, but considerable success in
saving affected infants has been achieved by using mechan-
ical ventilators that deliver air under pressure into the
alveoli. The most seriously affected newborns are treated
for several days with an extracorporeal membrane oxygen-
ator, which does the work of the lungs by oxygenating the
179
blood and removing carbon dioxide. The continual air

pressure provided by the ventilator prevents the collapse
of the air sacs. As the infant’s lungs mature and begin to
produce surfactant—usually within three to five days after
birth—the child is weaned from the ventilator. Most chil-
dren who survive have no aftereffects.
In adults, bacterial or viral pneumonia, exposure of the
lung to gases, aspiration of material into the lung (includ-
ing water in near-drowning episodes), or any generalized
septicemia (blood poisoning) or severe lung injury may
lead to sudden, widespread bilateral lung injury. This syn-
drome is known as acute respiratory distress syndrome of
adults. It was recognized as “shock lung” in injured sol-
diers evacuated by helicopter to regional military hospitals
during the Vietnam War. Many causes of respiratory dis-
tress syndrome of adults have been identified. Acute
respiratory distress syndrome carries about a 50 percent
mortality rate. Life-support treatment with assisted ven-
tilation rescues many patients, although superimposed
infection or multiple organ failure can result in death.
Recovery and repair of the lung may take months after
clinical recovery from the acute event.
Air Pollution
The disastrous fog and attendant high levels of sulfur
dioxide and particulate pollution (and probably also sulfu-
ric acid) that occurred in London in the second week of
December 1952 led to the deaths of more than 4,000 peo-
ple during that week and the subsequent three weeks.
Many, but not all, of the victims already had chronic heart
or lung disease. Prize cattle at an agricultural show also
died in the same period as a result of the air pollution. This
episode spurred renewed attention to this problem, which
had been intermittently considered since the 14th century
180
in England, and finally the passage of legislation banning

open coal burning, the factor most responsible for the
pollution. This form of pollution, common in many cities
using coal as heating fuel, is associated with excess mortal-
ity and increased prevalences of chronic bronchitis,
respiratory tract infections in the young and old, and pos-
sibly lung cancer. Today many industrial cities have
legislation restricting the use of specific fuels and mandat-
ing emission-control systems in factories.
In 1952 a different kind of air pollution was character-
ized for the first time in Los Angeles. The large number
of automobiles in that city, together with the bright sun-
light and frequently stagnant air, leads to the formation
of photochemical smog. This begins with the emission
Air pollution begins as emissions from sources such as industrial smokestacks.

The pollutants released into the air may impact the respiratory health of
people working in and living near such facilities. Photos.com/Jupiterimages
181
of nitrogen oxide during the morning commuting hour,

followed by the formation of nitrogen dioxide by oxygen-
ation, and finally, through a complex series of reactions in
the presence of hydrocarbons and sunlight, leads to the for-
mation of ozone and peroxyacetyl nitrite and other irritant
compounds. Eye irritation, chest irritation with cough, and
possibly the exacerbation of asthma occur as a result.
Modern air pollution consists of some combination of
the reducing form consequent upon sulfur dioxide emis-
sions and the oxidant form, which begins as emissions of
nitrogen oxides. Ozone is the most irritant gas known. In
controlled exposure studies it reduces the ventilatory
capability of healthy people in concentrations as low as
0.12 part per million. These levels are commonly exceeded
in many places, including Mexico City, Bangkok, and São
Paulo, where there is a high automobile density and the
meteorologic conditions favour the formation of photo-
chemical oxidants. Although acute episodes of communal
air exposure leading to demonstrable mortality are
unlikely, there is much concern over the possible long-
term consequences of brief but repetitive exposures to
oxidants and acidic aerosols. Such exposures are common
in the lives of millions of people, and the impact of these
exposures is an area of intense scientific investigation.
The indoor environment can be important in the
genesis of respiratory disease. In developing countries,
disease may be caused by inhalation of fungi from roof
thatch materials or by the inhalation of smoke when the
home contains no chimney. In developed countries, expo-
sure to oxides of nitrogen from space heaters or gas ovens
may promote respiratory tract infections in children.
Inhalation of tobacco smoke in the indoor environment
by nonsmokers impairs respiration, and repeated expo-
sures may lead to lung cancer. A tightly sealed house may
act as a reservoir for radon seeping in from natural sources.
182
Carbon Monoxide Poisoning
Carbon monoxide poisoning is a common and dangerous

hazard. British physiologist John Scott Haldane pioneered
the study of the effects of carbon monoxide at the end of
the 19th century, as part of his detailed analysis of atmo-
spheres in underground mines. Carbon monoxide is
produced by incomplete combustion, including combus-
tion of gas in automobile engines, and for a long period it
was a major constituent of domestic gas made from coal
(its concentration in natural gas is much lower).
When the carbon monoxide concentration in the
blood reaches 40 percent (when the hemoglobin is 40 per-
cent saturated with carbon monoxide, leaving only 60
percent available to bind to oxygen), the subject feels dizzy
and is unable to perform simple tasks. Judgment is also
impaired. Hemoglobin’s affinity for carbon monoxide is
200 times greater than for oxygen, and in a mixture of
these gases hemoglobin will preferentially bind to carbon
monoxide. For this reason, carbon monoxide concentra-
tions of less than 1 percent in inspired air seriously impair
oxygen-hemoglobin binding capacity. The partial pressure
of oxygen in the tissues in carbon monoxide poisoning is
much lower than when the oxygen-carrying capacity of
the blood has been reduced an equivalent amount by ane-
mia, a condition in which hemoglobin is deficient. The
immediate treatment for acute carbon monoxide poison-
ing is assisted ventilation with 100 percent oxygen.
The carbon monoxide inhaled by smokers who smoke
more than two packs of cigarettes a day may cause up to 10
percent hemoglobin saturation with carbon monoxide. A
4 percent increase in the blood carbon monoxide level in
patients with coronary artery disease is believed to shorten
the duration of exercise that may be taken before chest
pain is felt.
183
Acidosis
Acidosis is an abnormally high level of acidity, or low level

of alkalinity, in the body fluids, including the blood. There
are two primary types of acidosis: respiratory and meta-
bolic. Respiratory acidosis results from inadequate
excretion of carbon dioxide from the lungs. This may be
caused by severe acute or chronic lung disease, such as
pneumonia or emphysema, or by certain medications that
suppress respiration in excessive doses, such as general
anesthetic agents.
Metabolic acidosis occurs when acids are produced in
the body faster than they are excreted by the kidneys or
when the kidneys or intestines excrete excessive amounts
of alkali from the body. Causes of metabolic acidosis
include uncontrolled diabetes mellitus, shock, certain
drugs or poisons, and renal failure, among others. Both
respiratory and metabolic acidosis can be life-threatening
and often require immediate medical attention.
Alkalosis and Hyperventilation

Alkalosis is an abnormally low level of acidity, or high level
of alkalinity, in the body fluids, including the blood.
Alkalosis may be either metabolic or respiratory in origin.
Metabolic alkalosis results from either acid loss, which
may be caused by severe vomiting or by the use of potent
diuretics (substances that promote production of urine),
or bicarbonate gain, which may be caused by excessive
intake of bicarbonate or by the depletion of body fluid
volume. Respiratory alkalosis results from hyperventila-
tion, which may be caused by anxiety, asthma, congestive
heart failure, pulmonary embolism, or pneumonia.
Hyperventilation is defined as a sustained abnormal
increase in breathing. During hyperventilation the rate of
184
The alveoli and capillaries in the lungs exchange oxygen for carbon dioxide.
Imbalances in the exchange of these gases can lead to dangerous respiratory
disorders, such as respiratory acidosis or hyperventilation. In addition, accu-
mulation of fluid in the alveolar spaces can interfere with gas exchange, causing
symptoms such as shortness of breath. Encyclopædia Britannica, Inc.
185
removal of carbon dioxide from the blood is increased. As

the partial pressure of carbon dioxide in the blood
decreases, respiratory alkalosis ensues. In turn, alkalosis
causes constriction of the small blood vessels that supply
the brain. Reduced blood supply to the brain can cause a
variety of symptoms, including light-headedness and tin-
gling of the fingertips. Severe hyperventilation can cause
transient loss of consciousness.
Anxiety is the most common cause of hyperventila-
tion. Panic disorder, a severe episodic form of anxiety,
usually causes hyperventilation with resultant symptoms.
Treatment of recurrent hyperventilation begins with a
complete explanation by the patient of the condition and
the symptoms it causes. Some people benefit from psy-
chotherapy and medications to deal with the underlying
anxiety.
Hypoxia
Hypoxia is a condition of the body in which the tissues are
starved of oxygen. In its extreme form, where oxygen is
entirely absent, the condition is called anoxia. There are
four types of hypoxia: (1) the hypoxemic type, in which
the oxygen pressure in the blood going to the tissues is too
low to saturate the hemoglobin; (2) the anemic type, in
which the amount of functional hemoglobin is too small,
and hence the capacity of the blood to carry oxygen is too
low; (3) the stagnant type, in which the blood is or may be
normal but the flow of blood to the tissues is reduced or
unevenly distributed; and (4) the histotoxic type, in which
the tissue cells are poisoned and are therefore unable to
make proper use of oxygen. Diseases of the blood, the
heart and circulation, and the lungs may all produce some
form of hypoxia.
186
The hypoxemic type of hypoxia is due to one of two

mechanisms:
1. a decrease in the amount of breathable oxy-

gen—often encountered in pilots, mountain
climbers, and people living at high altitudes—
due to the reduced barometric pressure, or
2. cardiopulmonary failure in which the lungs are
unable to efficiently transfer oxygen from the
alveoli to the blood.
In the case of anemic hypoxia, either the total amount

of hemoglobin is too small to supply the body’s oxygen
needs, as in anemia or after severe bleeding, or hemoglo-
bin that is present is rendered nonfunctional. Examples of
the latter case are carbon monoxide poisoning and metho-
globinuria, in both of which the hemoglobin is so altered
by toxic agents that it becomes unavailable for oxygen
transport, and thus of no respiratory value.
Stagnant hypoxia, in which blood flow through the
capillaries is insufficient to supply the tissues, may be gen-
eral or local. If general, it may result from heart disease
that impairs the circulation, impairment of veinous return
of blood, or trauma that induces shock. Local stagnant
hypoxia may be due to any condition that reduces or pre-
vents the circulation of the blood in any area of the body.
Examples include Raynaud disease and Buerger disease,
which restrict circulation in the extremities; the applica-
tion of a tourniquet to control bleeding; ergot poisoning;
exposure to cold; and overwhelming systemic infection
with shock.
In histotoxic hypoxia the cells of the body are unable
to use the oxygen, although the amount in the blood
may be normal and under normal tension. Although
187
characteristically produced by cyanide, any agent that

decreases cellular respiration may cause it. Some of these
agents are narcotics, alcohol, formaldehyde, acetone, and
certain anesthetic agents.
Altitude Sickness
Altitude sickness, sometimes called mountain sickness, is
an acute reaction to a change from sea level or other low-
altitude environments to altitudes above 2,400 metres
(8,000 feet). Altitude sickness was recognized as early as
the 16th century. In 1878 French physiologist Paul Bert
demonstrated that the symptoms of altitude sickness are
the result of a deficiency of oxygen in the tissues of the
body. Mountain climbers, pilots, and persons living at high
altitudes are the most likely to be affected.
The symptoms of acute altitude sickness fall into four
main categories:
1. respiratory symptoms such as shortness of

breath upon exertion, and deeper and more
rapid breathing;
2. mental or muscular symptoms such as weakness,
fatigue, dizziness, lassitude, headache, sleep-
lessness, decreased mental acuity, decreased
muscular coordination, and impaired sight and
hearing;
3. cardiac symptoms such as pain in the chest,
palpitations, and irregular heartbeat; and
4. gastrointestinal symptoms such as nausea and
vomiting.
The symptoms usually occur within six hours to four

days after arrival at high altitude and disappear within
two to five days as acclimatization occurs. Although most
188
people gradually recover as they adapt to the low atmo-

spheric pressure of high altitude, some persons experience
a reaction that can be severe and, unless they return to low
altitude, possibly fatal.
At higher altitudes, the air becomes thinner and the
amount of breathable oxygen decreases. The lower baro-
metric pressures of high altitudes lead to a lower partial
pressure of oxygen in the alveoli, or air sacs in the lungs,
which in turn decreases the amount of oxygen absorbed
from the alveoli by red blood cells for transport to the
body’s tissues. The resulting insufficiency of oxygen in
the arterial blood supply causes the characteristic symp-
toms of altitude sickness. The main protection against
altitude sickness in aircraft is the use of pressurized air in
cabins. Mountain climbers often use a mixture of pure
oxygen and air to relieve altitude sickness while climbing
high mountains. In addition, the prophylactic use of the
diuretic acetazolamide initiated two to three days before
ascent may prevent or mitigate acute altitude sickness.
A more serious type of altitude sickness, high altitude
pulmonary edema (HAPE), occurs rarely among newcom-
ers to altitude but more often affects those who have
already become acclimated to high elevations and are
returning after several days at sea level. In pulmonary
edema, fluid accumulates in the lungs and prevents the
victim from obtaining sufficient oxygen. The symptoms
are quickly reversed when oxygen is given and the indi-
vidual is evacuated to a lower area.
Barotrauma and Decompression Sickness

Barotrauma is any of several injuries arising from changes
in pressure upon the body. Humans are adapted to live at
an atmospheric pressure of 760 mm of mercury (the pres-
sure at sea level), which differs from pressures experienced
189
in underwater environments and in the upper atmo-

spheres of space. Most body tissue is either solid or liquid
and remains virtually unaffected by pressure changes. In
certain cavities of the body, however, such as the ears,
sinuses, lungs, and intestines, there are air pockets that
either expand or contract in response to changes in pres-
sure. Abrupt expansion or contraction of closed internal
air spaces can injure or rupture surrounding tissues, such
as the eardrum.
A fatal form of barotrauma can occur in submariners
and divers. For example, if a person in a deeply submerged
submarine rapidly surfaces without exhaling during the
ascent, sudden expansion of air trapped within the thorax
can burst one or both lungs. Another form of barotrauma
may occur during mechanical ventilation for respiratory
failure. Air pumped into the chest by the machine can
overdistend and rupture a diseased portion of the lung.
Subsequent breaths delivered by the ventilator are then
driven into the mediastinum (the space between the
lungs), the pleural spaces, or under the skin of the neck,
face, and torso, causing subcutaneous emphysema (the
trapping of air under the skin or in tissues).
In decompression sickness (also called “the bends”
or caisson disease) the formation of gas bubbles in the
body because of rapid transition from a high-pressure
environment to one of lower pressure causes a variety
of physiological effects. Pilots of unpressurized aircraft,
underwater divers, and caisson workers are highly sus-
ceptible to the sickness because their activities subject
them to pressures different from the normal atmospheric
pressure experienced on land. At atmospheric pressure
the body tissues contain, in solution, small amounts
of the gases that are present in the air. When a pilot
ascends to a higher altitude, the external pressures upon
his or her body decrease, and these dissolved gases come
190
out of solution. If the ascent is slow enough, the gases have

time to diffuse from the tissues into the bloodstream. The
gases then pass to the respiratory tract and are exhaled
from the body.
The pathogenesis of decompression sickness begins
both with the mechanical effects of bubbles and their
expansion in the tissues and blood vessels and with the
surface effects of the bubbles upon the various compo-
nents of the blood at the blood–gas interface. The lung
plays a significant role in the pathogenesis and natural his-
tory of this illness and may contribute to the clinical
picture. Shallow, rapid respiration, often associated with a
sharp retrosternal pain on deep inspiration, signals the
onset of pulmonary decompression sickness, the “chokes.”
The major component of air that causes decompres-
sion maladies is nitrogen. The oxygen breathed is used up
by the cells of the body and the waste product carbon diox-
ide is continuously exhaled. Conversely, nitrogen merely
accumulates in the body until the tissue becomes saturated
at the ambient pressure. When the pressure decreases, the
excess nitrogen is released. Nitrogen is much more soluble
in fatty tissue than in other types. Therefore, tissues with a
high fat content (lipids) tend to absorb more nitrogen than
do other tissues. The nervous system is composed of about
60 percent lipids. Bubbles forming in the brain, spinal
cord, or peripheral nerves can cause paralysis and convul-
sions (diver’s palsy), difficulties with muscle coordination
and sensory abnormalities (diver’s staggers), numbness,
nausea, speech defects, and personality changes. When
bubbles accumulate in the joints, pain is usually severe and
mobility is restricted. The term bends is derived from this
affliction, as the affected person commonly is unable to
straighten joints.
Small nitrogen bubbles trapped under the skin may
cause a red rash and an itching sensation known as diver’s
191
itches. Usually these symptoms pass in 10 to 20 minutes.

Excessive coughing and difficulty in breathing, known as
the chokes, indicate nitrogen bubbles in the respiratory
system. Other symptoms include chest pain, a burning
sensation while breathing, and severe shock. Relief from
decompression sickness usually can be achieved only by
recompression in a hyperbaric chamber followed by grad-
ual decompression, but this process is not always able to
reverse damage to tissues.
Thoracic Squeeze
Thoracic squeeze, or lung squeeze, is a type of baro-
trauma involving compression of the lungs and thoracic
cavity. It most commonly occurs during a breath-holding
dive underwater. During the descent, an increase in pres-
sure causes air spaces and gas pockets within the body to
compress. Because the lung tissue is elastic and inter-
spersed with tubules and sacs of air, it is capable of some
enlargement when air is inhaled and some shrinkage
when it is exhaled. Too much air causes rupture of lung
tissue, while too little air causes compression and col-
lapse of the lung walls.
As external pressure on the lungs is increased in a
breath-holding dive (in which the diver’s only source of
air is that held in his lungs), the air inside the lungs is
compressed, and the size of the lungs decreases. If one
descends to a depth of about 30 metres (100 feet), the
lung shrinks to about one-fourth its size at the surface.
Excessive compression of the lungs in this manner causes
tightness and pain in the thoracic cavity. If compression
continues, the delicate lung tissue may rupture and allow
tissue fluids to enter the lung spaces and tubules. The
outer linings of the lungs (pleural sacs) may separate from
the chest wall, and the lung may collapse.
192
The predominant symptom felt by the diver is pain

when the pressure becomes too great, which can be
relieved by ascending. If the thoracic squeeze has been
sufficient to cause lung damage, the diver may have diffi-
culty in breathing, may exhale frothy blood, and may even
become unconscious. Artificial respiration may be neces-
sary if the breathing has stopped. Any symptoms of
thoracic squeeze call for prompt medical attention.
Animals such as seals and whales that descend to much
greater depths than humans on a single breath of air have
special adaptations to help them. The sperm whale is
reported to dive to about 1,000 metres (3,300 feet), more
than 10 times the depth that humans can tolerate. These
aquatic mammals have been found to have more elastic
chest cavities than humans; their lungs, even when
reduced, do not separate from the chest wall; and their
bodies are adapted to use the gases in the bloodstream
more conservatively.
Drowning
Drowning is suffocation by immersion in a liquid, usually
water. Water closing over the victim’s mouth and nose cuts
off the body ’s supply of oxygen. Deprived of oxygen the
victim stops struggling, loses consciousness, and gives up
the remaining tidal air in his or her lungs. There the heart
may continue to beat feebly for a brief interval, but even-
tually it ceases. Until recently, the oxygen deprivation that
occurs with immersion in water was believed to lead to
irreversible brain damage if it lasted beyond three to seven
minutes. It is now known that victims immersed for an
hour or longer may be totally salvageable, physically and
intellectually, although they lack evidence of life, having
no measurable vital signs—heartbeat, pulse, or breath-
ing—at the time of rescue. A fuller appreciation of the
193
body’s physiological defenses against drowning has

prompted modification of traditional therapies and inten-
sification of resuscitative efforts, so that many people who
once would have been given up for dead are being saved.
Although asphyxiation (lack of oxygen that causes
unconsciousness) is common to all immersion incidents,
actual aspiration of water into the lungs may or may not
occur. Up to 15 percent of drownings are “dry,” presumably
because the breath is held or because a reflex spasm of the
larynx seals off the airway inlet at the throat. When aspi-
ration does occur, the volume of fluid entering the lungs
rarely exceeds a glassful. The lungs “fill with water” chiefly
because of an abnormal accumulation of body fluids (pul-
monary edema) that is a secondary complication of oxygen
deprivation. Often, quantities of water are swallowed and
later vomited spontaneously or during resuscitative pro-
cedures. Vomiting after the protective laryngeal spasm has
subsided can lead to aspiration of stomach contents.
A natural biological mechanism that is triggered by
contact with extremely cold water, known as the mamma-
lian diving reflex, enhances survival during submersion,
thus permitting seagoing mammals to hunt for long peri-
ods underwater. Scientists have determined that vestiges
of the reflex persist in humans. The mechanism is power-
ful in children. It diverts blood from the limbs, abdomen,
and surface areas of the body to the heart and the brain. It
also causes an interruption of respiratory efforts and
reduces the rate of the heartbeat. Even though the heart
functions at a slower rate, in other respects it performs
normally. Actual arrest of circulatory processes is a rela-
tively late development in the drowning sequence. In this
suspended state, intracranial blood retains sufficient oxy-
gen to meet the brain’s reduced metabolic needs, despite a
total absence of respiratory gas exchange.
194
In warm water the body’s need for oxygen is increased,

so the oxygen deprivation caused by immersion is rapidly
lethal or permanently damaging to the brain. Such warm-
water drownings occur commonly in domestic bathtubs.
Immersion in icy water causes body temperature and
metabolism to fall rapidly (the thermal conductivity of
water is 32 times greater than that of air). Immersion
hypothermia—below normal body temperature—reduces
cellular activity of tissues, slows the heart rate, and
promotes unconsciousness. None of these effects is immi-
nently life-threatening; survival following hypothermic
coma is almost 75 percent. Rescue teams now continue
the benefits of cold-water protection with “therapeutic
hypothermia.” “Lifeless” immersion victims with core
temperatures as low as 62.6 °F (17 °C) have survived.
195
CHAPTER7
APPROACHES TO RESPIRATORY
EVALUATION AND TREATMENT
T he study of the anatomy, physiology, and pathology of
the human respiratory system is known as pulmonol-
ogy, or respiratory medicine. One of the most important
advances in the history of respiratory medicine was the
development of the stethoscope in 1816 by French physi-
cian René-Théophile-Hyacinthe Laënnec. This instrument
enabled physicians to more precisely diagnose diseases of
the chest and heart.
Today, many technological advances, particularly con-
cerning techniques employing X-ray imaging or endoscopy,
have contributed to improvements in the diagnosis and
evaluation of respiratory disease. Likewise, drugs such as
decongestants and antibiotics have substantially improved
the treatment of allergic and infectious respiratory dis-
eases. In addition, modern respiratory medicine is
intimately associated with ongoing scientific research into
the cellular and molecular processes that underlie respira-
tory function. This expansion of scientific understanding
has enabled important progress in respiratory medicine,
especially in the area of disease prevention.
recognizing the signs and

syMptoMs of disease
The symptoms of lung disease are relatively few. Cough is
a particularly important sign of all diseases that affect any
part of the bronchial tree. A cough productive of sputum
is the most important manifestation of inflammatory or
196
7 Approaches to Respiratory Evaluation and Treatment 7
malignant diseases of the major airways, of which bron-

chitis is a common example. In severe bronchitis the
mucous glands lining the bronchi enlarge greatly, and,
commonly, 30 to 60 ml of sputum are produced in a
24-hour period, particularly in the first two hours after
awakening in the morning. An irritative cough without
sputum may be caused by extension of malignant disease
to the bronchial tree from nearby organs. The presence of
blood in the sputum (hemoptysis) is an important sign
that should never be disregarded. Although it may result
simply from an exacerbation of an existing infection, it
may also indicate the presence of inflammation, capillary
damage, or a tumour. Hemoptysis is also a classic sign of
tuberculosis of the lungs.
The second most important symptom of lung disease
is dyspnea, or shortness of breath. This sensation, of
complex origin, may arise acutely, as when a foreign body
is inhaled into the trachea, or with the onset of a severe
attack of asthma. More often, it is insidious in onset and
slowly progressive. What is noted is a slowly progressive
difficulty in completing some task, such as walking up a
flight of stairs, playing golf, or walking uphill. The short-
ness of breath may vary in severity, but in diseases such as
emphysema, in which there is irreversible lung damage, it
is constantly present. It may become so severe as to
immobilize the victim, and tasks such as dressing cannot
be performed without difficulty. Severe fibrosis of the
lung, resulting from occupational lung disease or arising
from no identifiable antecedent condition, may also
cause severe and unremitting dyspnea. Dyspnea is also an
early symptom of congestion of the lung as a result of
impaired function of the left ventricle of the heart. When
this occurs, if the right ventricle that pumps blood
through the lungs is functioning normally, the lung capil-
laries become engorged, and fluid may accumulate in
197
small alveoli and airways. It is commonly dyspnea that

first causes a patient to seek medical advice, but absence
of the symptom does not mean that serious lung disease
is not present, since, for example, a small lung cancer that
is not obstructing an airway does not produce shortness
of breath.
Chest pain may be an early symptom of lung disease,
but it is most often associated with an attack of pneumo-
nia, in which case it is due to an inflammation of the pleura
that follows the onset of the pneumonic process. Pain
associated with inflammation of the pleura is characteris-
tically felt when a deep breath is taken. The pain disappears
when fluid accumulates in the pleural space, a condition
known as a pleural effusion. Acute pleurisy with pain may
signal a blockage in a pulmonary vessel, which leads to
acute congestion of the affected part. For example, pul-
monary embolism, the occlusion of a pulmonary artery by
a fat deposit or by a blood clot that has dislodged from a
site elsewhere in the body, can cause pleurisy. Sudden
blockage of a blood vessel injures the lung tissue to which
the vessel normally delivers blood. In addition, severe
chest pain may be caused by the spread of malignant dis-
ease to involve the pleura, or by a tumour that arises from
the pleura itself, such as a mesothelioma. Severe, intrac-
table pain caused by such conditions may require surgery
to cut the nerves that supply the affected segment.
Fortunately, pain of this severity is rare.
To these major symptoms of lung disease—coughing,
dyspnea, and chest pain—may be added several others. A
wheeziness in the chest may be heard. This is caused by
narrowing of the airways, such as occurs in asthma. Some
diseases of the lung are associated with the swelling of the
fingertips (and, rarely, of the toes) called “clubbing.”
Clubbing may be a feature of bronchiectasis (chronic
inflammation and dilation of the major airways), diffuse
198
fibrosis of the lung from any cause, and lung cancer. In the
case of lung cancer, this unusual sign may disappear after
surgical removal of the tumour. In some lung diseases, the
first symptom may be a swelling of the lymph nodes that
drain the affected area, particularly the small nodes above
the collarbone in the neck; enlargement of the lymph
nodes in these regions should always lead to a suspicion of
intrathoracic disease. Not infrequently, the presenting
symptom of a lung cancer is caused by spread of the
tumour to other organs. Thus, a hip fracture from bone
metastases, cerebral signs from intracranial metastases, or
jaundice from liver involvement may all be the first evi-
dence of a primary lung cancer, as may sensory changes in
the legs, since a peripheral neuropathy may also be the
presenting evidence of these tumours.
The generally debilitating effect of many lung diseases
is well recognized. A person with active lung tuberculosis
or with lung cancer, for example, may be conscious of only
a general feeling of malaise, unusual fatigue, or seemingly
minor symptoms as the first indication of disease. Loss
of appetite and loss of weight, a disinclination for physi-
cal activity, general psychological depression, and some
symptoms apparently unrelated to the lung, such as mild
indigestion or headaches, may be diverse indicators of lung
disease. Not infrequently, the patient may feel as one does
when convalescent after an attack of influenza. Because
the symptoms of lung disease, especially in the early stage,
are variable and nonspecific, physical and radiographic
examination of the chest are an essential part of the evalu-
ation of persons with these complaints.
Methods of investigation
Physical examination of the chest remains important, as
it may reveal the presence of an area of inflammation, a
199
pleural effusion, or an airway obstruction. Methods of

examination include physical inspection and palpation
for masses, tender areas, and abnormal breathing pat-
terns; percussion to gauge the resonance of the underlying
lung; and auscultation (listening) with a stethoscope to
determine pitch and loudness of breath sounds. The
sounds detected with a stethoscope may reveal abnormali-
ties of the airways, the lung tissue, or the pleural space.
Examination of the sputum for bacteria allows the identi-
fication of many infectious organisms and the institution
of specific treatment; sputum examination for malignant
cells is occasionally helpful.
The conventional radiological examination of the
chest has been greatly enhanced by the technique of com-
puterized tomography (CT). This technique produces a
complete picture of the lungs by using X-rays to create
two-dimensional images that are integrated into one
image by a computer. While the resolution of computer-
ized tomography is much better than most other
visualization techniques, lung ventilation and perfusion
scanning can also be helpful in detecting abnormalities of
the lungs. In these techniques, a radioactive tracer mole-
cule is either inhaled, in the case of ventilation scanning,
or injected, in the case of perfusion scanning. The ventila-
tion scan allows visualization of gas exchange in the
bronchi and trachea, and the perfusion scan allows visual-
ization of the blood vessels in the lungs. The combined
results from ventilation and perfusion scanning are impor-
tant for the detection of focal occlusion of pulmonary
blood vessels by pulmonary emboli.
Although magnetic resonance imaging (MRI) plays a
limited role in examination of the lung, because the tech-
nique is not well suited to imaging air-filled spaces, MRI is
useful for imaging the heart and blood vessels within the
200
thorax. Positron emission tomography (PET) is used to

distinguish malignant lung tissue from scar tissue on tis-
sues such as the lymph nodes. Flexible fibre-optic
bronchoscopes that can be inserted into the upper airway
through the mouth are used to examine the larynx, tra-
chea, and major bronchi. By feeding a surgical instrument
through a special channel of the bronchoscope, physicians
can collect fluid and small tissue samples from the airways.
Tissue samples are examined for histological changes that
indicate certain diseases and are cultured to determine
whether harmful bacteria are present.
A number of tests are available to determine the
functional status of the lung and the effects of disease
on pulmonary function. Spirometry, the measurement
of the rate and quantity of air exhaled forcibly from a
full respiration, allows measurement of the ventilation
capacity of the lungs and quantification of the degree of
airflow obstruction. Ventilatory capability can be mea-
sured with a peak flow meter, which is often used in field
studies. More complex laboratory equipment is neces-
sary to measure the volumes of gas in the lung; the
distribution of ventilation within the lung; airflow resis-
tance; the stiffness of the lung, or the pressure required
to inflate it; and the rate of gas transfer across the lung,
which is commonly measured by recording the rate of
absorption of carbon monoxide into the blood (hemo-
globin has a high affinity for carbon monoxide). Arterial
blood gases and pH values indicate the adequacy of oxy-
genation and ventilation and are routinely measured in
patients in intensive care units. Tests of exercise capa-
bility, in which workload, total ventilation, and gas
exchange are compared before, during, and after exer-
cise, are useful in assessing functional impairment and
disability.
201
A spirometry test measures lung capacity and degree of airflow obstruction.

David McNew/Getty Images
Pulmonary Function Test
A pulmonary function test is a procedure used to measure

various aspects of the working capacity and efficiency of
the lungs and to aid in the diagnosis of pulmonary disease.
There are two general categories of pulmonary function
tests: (1) those that measure ventilatory function, or lung
volumes and the process of moving gas in and out of the
lungs from ambient air to the alveoli (air sacs), and (2)
those measuring respiratory function, or the transfer of
gas between the alveoli and the blood. Tests of ventilatory
function include the following measurements: residual
202
volume (RV), air remaining within the chest after a maxi-

mal expiration; functional residual capacity (FRC), the
resting lung volume, or air within the chest at the end of a
quiet expiration; tidal volume, volume of a breath; vital
capacity, maximum air volume that can be expelled after a
maximum inspiration; and total lung capacity (TLC), air
volume within the chest in full inspiration. Except for the
residual volume, which is measured by a dilution method,
all the other volumes may be recorded with a spirometer;
breathing movements may also be registered graphically
on a spirogram.
Ventilation tests, which measure the capacity of the
lungs to move air in and out, include maximal voluntary
ventilation (MVV), maximal air volume expelled in 12 to
15 seconds of forced breathing; forced expiratory volume
(FEV), maximum air volume expelled in a time interval;
and maximal expiratory flow rate (MEFR), maximal flow
rate of a single expelled breath, expressed in litres of air
per minute. Tests of respiratory function include the mea-
surement of blood oxygen and carbon dioxide and the rate
at which oxygen passes from the alveoli into the small
blood vessels, or capillaries, of the lungs.
Chest X-ray
X-ray imaging is a valuable diagnostic technique used in
medicine. This approach produces an image known as a
roentgenogram (or X-ray image) of internal structures.
The image is made by passing X-rays through the body to
produce a shadow image on specially sensitized film. The
roentgenogram is named after German physicist Wilhelm
Conrad Röntgen, who discovered X-rays in 1895.
One of the most common screening roentgenograms
is the chest film, taken to look for infections such as
203
tuberculosis and conditions such as heart disease and

lung cancer. Treatment of tuberculosis detected by a
roentgenogram can prevent more extensive infection,
but, unfortunately, this technique is of little value in
screening for lung cancer because the stage at which the
disease is detectable by this method is too far advanced
for treatment to be of value.
Lung Ventilation/Perfusion Scan

A lung ventilation/perfusion scan, or VQ (ventilation quo-
tient) scan, is a test that measures both air flow (ventilation)
and blood flow (perfusion) in the lungs. Lung ventilation/
perfusion scanning is used most often in the diagnosis
of pulmonary embolism, the blockage of one of the pul-
monary arteries or of a connecting vessel. Pulmonary
embolism is caused by a clot or an air bubble that has
become lodged within a vessel or by the accumulation of
fat along the inner walls of the vessel, thereby narrowing
the passageway and hindering the flow of blood. The pro-
cedure is also used to accurately identify damaged regions
of lung tissue prior to surgery to remove the tissue. This
approach may be taken for patients with advanced or rap-
idly spreading lung cancer.
Lung ventilation/perfusion scanning uses radioiso-
topes to trace the movement of air and blood through the
lungs. To track the movement of air, the patient inhales a
mixture of oxygen and nitrogen containing small amounts
of radioactive xenon or technetium. A scanner that con-
tains a radiation-sensitive camera is then used to collect
images of the gamma rays emitted from the tracer as it
circulates through the lungs. For the perfusion part of the
scan, the patient receives an injection into the blood-
stream of a radioactive albumin tracer (usually labeled
204
with technetium), and another set of images is taken with

the scanner.
In both ventilation and perfusion scans, normal air
and blood flow are reflected in the even distribution of
tracers within the lungs. Thus, the ventilation and perfu-
sion scans match for a person with healthy lungs. In
contrast, a mismatch between the two scans is indicative
of disease. The appearance of hot spots, or areas where
the tracers become highly concentrated and therefore
produce bright areas in the images, highlight places within
the lungs where air or blood have accumulated abnor-
mally. Areas in the images known as cold spots appear
very dark and point to regions within the lungs where
tracers are relatively scarce. Depending on whether a dark
area appears in a ventilation scan or in a perfusion scan,
the tissues affected will be either oxygen- or blood-
deprived. Nutrient deprivation renders the tissue highly
susceptible to death.
Although the tracers used in lung ventilation/perfu-
sion scanning are radioactive, the levels of radioactivity
are exceptionally low and pose a very small risk to patients.
In general, persons for whom the scanning procedure is
not recommended include women who are pregnant or
who are breast-feeding. If the results of lung ventilation/
perfusion scanning reveal that a patient is at high risk for
pulmonary embolism, he or she may subsequently undergo
more invasive procedures, including angiography.
Bronchoscopy
Bronchoscopy is a medical examination of the bronchial
tissues using a lighted instrument known as a bron-
choscope. The procedure is commonly used to aid the
diagnosis of respiratory disease in persons with persistent
205
The trachea and major bronchi of the human lungs. Encyclopædia

Britannica, Inc.
206
cough or who are coughing up blood, as well as in persons

who have abnormal chest findings following computer-
ized axial tomography scanning or X-ray examination.
Bronchoscopy is also employed to remove foreign objects
from the airways, to deliver certain therapeutic agents
directly into the lungs, and to assist in the placement of
stents (tubes, typically made of expandable wire mesh) or
in the resection (removal) of tissue in cases in which can-
cerous growths block the airways.
There are two types of bronchoscopes. The most fre-
quently used scope consists of a flexible tube containing a
bundle of thin fibre-optic rods that project light onto the
tissues being examined. A flexible bronchoscope may be
passed through the nose to examine the upper airways or
through the mouth to examine the trachea and lungs.
Flexible scopes, because of their ability to bend and twist,
can be used to examine bronchial passageways down to
the level of the tertiary bronchi—the smallest passages
preceding the bronchioles. The second type of scope,
known as a rigid bronchoscope, consists of a metal tube
that has a wide suction channel, which enables large vol-
umes of fluid (e.g., blood) to be removed during an
examination. Although rigid bronchoscopes have been
replaced by flexible scopes for the majority of procedures,
they remain superior for specific applications. They are
used most often to examine the central airways when
blockage by a foreign body is suspected and to resect dis-
eased tissue in a procedure known as laser bronchoscopy.
All bronchoscopes can be fitted with a small video camera
that enables real-time visualization of the procedure. In
addition, both flexible and rigid scopes have a channel
through which instruments can be passed. The latter fea-
ture is commonly employed for biopsy—the collection of
tissues for histological study.
207
Flexible bronchoscopy of the upper airways generally

requires the use of a local anesthetic to numb the tissues.
In contrast, rigid bronchoscopy, because of the discom-
fort caused by the device, necessitates the use of general
anesthesia, which can cause side effects in some people,
including nausea and vomiting, upon waking. In addition,
there are several important risks associated with the bron-
choscopy procedure itself. For example, the movement of
a bronchoscope through the airways often scratches super-
ficial tissues, causing them to bleed. Bleeding is especially
common following biopsy. In most cases, however, bleed-
ing subsides without the need for medical intervention.
The bronchoscope or the removal of tissue for biopsy
may lead to the perforation of lung tissue, causing a con-
dition known as pneumothorax, in which air enters the
space between the pleural membranes lining the lungs and
thoracic cavity. Another risk factor associated with bron-
choscopy is the introduction of infectious agents into the
lungs, which occurs when the instrument is not sanitized
properly.
Mediastinoscopy
Mediastinoscopy is a medical examination of the medi-
astinum using a lighted instrument known as a
mediastinoscope. Because the region of the mediasti-
num contains the heart, trachea, esophagus, and thymus
gland, as well as a set of lymph nodes, mediastinoscopy
can be used to evaluate and diagnose a variety of thoracic
diseases, including tuberculosis and sarcoidosis (a dis-
ease characterized by the formation of small grainy
lumps within tissues). It fulfills an especially important
role in the detection and diagnosis of cancers affecting
the thoracic cavity, serving as one of the primary
208
methods by which tissue samples are collected from the

mediastinal lymph nodes for the staging of lung cancer.
Staging involves the investigation of cells to assess the
degree to which cancer has spread. Mediastinoscopy is
also frequently used in conjunction with noninvasive
cancer-detection techniques, including computerized
axial tomography and positron emission tomography.
During mediastinoscopy, which is performed under
general anesthesia, a surgeon first makes a small inci-
sion in the patient’s neck, immediately above the
sternum. This step of the procedure is known as medi-
astinotomy. A mediastinoscope—a thin, light-emitting,
flexible instrument—is then passed through the inci-
sion and into the space between the lungs. By carefully
maneuvering the scope in the space, the doctor is able
to investigate the surfaces of the various structures. A
video camera attached to the scope aids in the position-
ing of the instrument and in the visual examination of
the tissues. In cancer staging, tissue samples from the
lymph nodes are collected by passing a biopsy instru-
ment through a channel in the scope. This may also be
performed for other tissues in the region that display
signs of disease, such as abnormal growths or inflam-
mation. The biopsy samples are then investigated for
evidence of abnormalities, particularly for cellular
defects associated with cancer and for the presence of
infectious organisms.
Most patients recover within several days following
mediastinoscopy, and the procedure is associated with a
very low risk of complications. Severe complications—
such as bleeding, pneumothorax (damage to the lungs that
causes the leakage of air into the space between the lungs
and thoracic cavity), infection, or paralysis of the vocal
cords—occur in approximately 1 to 3 percent of patients.
209
Types of respiratory therapy

Respiratory therapy is primarily concerned with assisting
or improving the respiratory function of individuals with
acute or chronic lung disease. There are different methods
of treatment employed in respiratory therapy, each of
which may be tailored to a specific disease. One of the
conditions frequently dealt with is obstruction of breath-
ing passages, in which chest physiotherapy is used to
facilitate clearing the airway of mucus or liquid secretion
by suction. Chest percussion, performed manually or by
means of a handheld percussor or vest, produces vibra-
tions that help to loosen and mobilize secretions. Postural
drainage is a technique in which the forces of gravity are
used to promote the drainage of obstructing secretions.
Other forms of respiratory therapy include the use of
aerosol treatments to relieve bronchospasm. Water is a
major therapeutic agent in bronchopulmonary disease
and may be used in the form of cold steam, hot steam, or a
fog (as in an oxygen tent or a croup tent). Aerosol humidi-
fiers called nebulizers may be powered by compressor
machinery or by a hand-squeezed bulb to project medica-
tion or water spray into the airway. Ultrasonic equipment
may be used to propel very fine particles directly into the
lungs, as in treatment of cystic fibrosis. Medications, such
as bronchodilators, mucolytics, and antibiotics, can also
be administered in an inhaled mist by means of an ultra-
sonic nebulizer.
Therapy may involve the administration of gases for
inhalation. Oxygen may be administered in controlled
amounts to assist laboured breathing. A mixture of helium
and oxygen is used to treat some diseases of airway
obstruction. In addition, respiratory therapists are experts
in the setup, adjustment, and maintenance of mechanical
ventilators.
210
Drug Therapies
There are many different types of drugs that may be used

in the treatment of respiratory diseases. However, there
are three groups, decongestants, antihistamines, and anti-
biotics, that are of particular importance in the routine
treatment of respiratory illness. In countries such as the
United States, decongestants and antihistamines are avail-
able over the counter, and thus they are used by many
people. The relative safety and efficacy of these drugs has
made them generally reliable medications. Antibiotics
represent a group of drugs that revolutionized respiratory
medicine following the introduction of penicillin in the
1940s. Of special importance in the treatment of respira-
tory infections such as bacterial pneumonia is a class of
antibiotics known as macrolides. Though the use of anti-
biotics in the treatment of minor respiratory infections is
today a controversial issue, due to the emergence of resis-
tant organisms, these agents remain valuable in reducing
mortality rates from respiratory diseases that at one time
caused certain death in humans.
Decongestants
Decongestants are drugs used to relieve swelling of the
nasal mucosa accompanying such conditions as the com-
mon cold and hay fever. When administered in nasal
sprays or drops or in devices for inhalation, decongestants
shrink the mucous membranes lining the nasal cavity by
contracting the muscles of blood vessel walls, thus reduc-
ing blood flow to the inflamed areas. The constricting
action chiefly affects the smallest arteries, the arterioles,
although capillaries, veins, and larger arteries respond to
some degree.
Decongestants are sympathomimetic agents. That is,
they mimic the effects of stimulation of the sympathetic
211
division of the autonomic nervous system. One of the

chief drugs of the group is epinephrine, a neurotransmit-
ter produced by the adrenal gland that is released at
sympathetic nerve endings when the nerves are stimu-
lated. The effect of its decongestant action resembles the
blanching of the skin that occurs with anger or fright, in
which epinephrine constricts the blood vessels of the skin.
The effectiveness of the other decongestants results
from their chemical similarity to epinephrine. The oldest
and most important decongestant is ephedrine, an alka-
loid originally obtained from the leaves of ma huang, any of
several species of shrubs of the genus Ephedra, which has
been used in Chinese medicine for more than 5,000 years.
Ephedrine and other decongestants are made by chemical
synthesis. They include phenylephrine hydrochloride,
amphetamine and several derivatives, and naphazoline
hydrochloride. Because none of them has a sustained
effect, they must be used repeatedly; too frequent use,
however, results in absorption into the bloodstream, caus-
ing anxiety, insomnia, dizziness, headache, or heart
palpitations.
Antihistamines
Antihistamines are drugs that selectively counteract the
pharmacological effects of histamine, following its release
from certain large cells (mast cells) within the body.
Antihistamines replace histamine at one or the other of
the two receptor sites at which it becomes bound to
various susceptible tissues, thereby preventing histamine-
triggered reactions under such conditions as stress,
inflammation, and allergy.
The antihistamines that were the first to be intro-
duced are ones that bind at the so-called H1 receptor
sites. They are therefore designated H1-blocking agents
and oppose selectively all the pharmacological effects of
212
histamine except those on gastric secretion. The devel-

opment of these antihistamines dates from about 1937,
when French researchers discovered compounds that
protected animals against both the lethal effects of hista-
mine and those of anaphylactic shock. The first
antihistamines were derivatives of ethylamine. Aniline-
type compounds, tested later and found to be more
potent, were too toxic for clinical use. In 1942, the fore-
runner of most modern antihistamines (an aniline
derivative called Antergan) was discovered; subsequently,
compounds that were more potent, more specific, and
less toxic were prepared. More than 100 antihistaminic
compounds soon became available for treating patients.
Because histamine is involved in the production of
some symptoms of allergy and anaphylaxis, antihista-
mines can control certain allergic conditions, among
them hay fever and seasonal rhinitis. Nasal irritation and
watery discharge are most readily relieved. Persons with
urticaria, edema, itching, and certain sensitivity reac-
tions respond well. Antihistamines are not usually
beneficial in treating the common cold and asthma.
Antihistamines with powerful antiemetic properties are
used in the treatment of motion sickness and vomiting.
Used in sufficiently large doses, nearly all antihistamines
produce undesirable side effects. The incidence and
severity of the side effects depend both on the patient
and on the properties of the specific drug. The most
common side effect in adults is drowsiness. Other side
effects include gastrointestinal irritation, headache,
blurred vision, and dryness of the mouth. If a patient’s
condition does not improve after three days of treatment
with antihistamines, it is unlikely that he or she will ben-
efit from them. Antihistamines are readily absorbed from
the alimentary tract, and most are rendered inactive by
monoamine oxidase enzymes in the liver.
213
During the 1970s an H2-blocking agent, cimetidine

(Tagamet) was introduced. Compounds of this class sup-
press histamine-induced gastric secretion and have proved
extremely useful in treating gastric and duodenal ulcers.
Antibiotics
Antibiotics are among the most medically valuable drugs
available in the modern era, and they are especially impor-
tant in the treatment of bacterial respiratory infections.
The principle governing the use of antibiotics is to ensure
that the patient receives one to which the target bacte-
rium is sensitive, at a high enough concentration to be
effective (but not cause side effects), and for a sufficient
length of time to ensure that the infection is totally eradi-
cated. Antibiotics vary in their range of action. Some are
highly specific, whereas others, such as the tetracyclines,
act against a broad spectrum of different bacteria.
Antibiotics known as macrolides (e.g., erythromycin,
clarithromycin, azithromycin) are particularly effective in
the treatment of bacterial respiratory infections. These
drugs are usually administered orally, but they can be given
parenterally. Macrolides, which inhibit bacterial protein
synthesis, are valuable in treating pharyngitis and pneumo-
nia caused by Streptococcus in persons sensitive to penicillin.
They are also used in treating pneumonias caused either
by Mycoplasma species or by Legionella pneumophila (the
organism that causes Legionnaire disease). Macrolides are
also used to treat pharyngeal carriers of Corynebacterium
diphtheriae, the bacillus responsible for diphtheria.
Oxygen Therapy
The medical administration of oxygen is an important
means of treating respiratory disease. Oxygen therapy is
used for acute conditions, in which tissues such as the
214
brain and heart are at risk of oxygen deprivation, as well as

for chronic diseases that are characterized by sustained
low blood oxygen levels (hypoxemia).
In emergency situations, oxygen may be adminis-
tered by citizen responders via mouth-to-mouth breaths
in cardiopulmonary resuscitation (CPR) or by emer-
gency medical personnel via a face mask placed over the
victim’s mouth and nose that is attached to a small, por-
table compressed-gas oxygen cylinder. For patients
affected by chronic lung diseases, such as chronic
obstructive pulmonary disease (COPD), home oxygen
therapy may be prescribed by a physician. In both the
hospital and the home settings, oxygen may be delivered
through a face mask or through a nasal cannula, a device
inserted into the nostrils that is connected by tubing to
an oxygen system. Some patients may require oxygen
administration via a transtracheal catheter, which is
inserted directly into the trachea by way of a hole made
surgically in the neck.
Another form of therapy, known as hyperbaric oxygen
therapy (HBOT), employs a pressurized oxygen chamber
(hyperbaric chamber) into which pure oxygen is delivered
via an air compressor. The high-pressure atmosphere has
been shown to reduce air bubbles in the blood of persons
affected by conditions such as air embolism (artery or vein
blockage by a gas bubble) and decompression sickness. In
addition, the high concentrations of oxygen made available
to tissues have been shown to help stimulate the growth
of new blood vessels (angiogenesis) in healing wounds and
to slow the progression of infections caused by certain
anaerobic bacteria. HBOT has been promoted as an alter-
native therapy for certain conditions. These applications
are controversial, however, because the procedure can
potentially stimulate the generation of DNA-damaging
free radicals.
215
There are various stationary and portable oxygen-

storage systems that can be used in the hospital or the
home. Oxygen concentrators, which draw in surround-
ing air and filter out nitrogen, provide a method of storing
oxygen at concentrations greater than that occurring in
ambient air. The stored oxygen can then be used by the
patient when needed and is readily replenished. Stationary
and portable oxygen concentrators have been developed
for use in the home. Another form of oxygen storage is
in compressed-gas cylinders, which maintain oxygen
under high pressure and require the use of a regulator to
modulate the flow of gas from the cylinder to the patient.
Gas cylinders are often used in conjunction with oxygen-
conserving devices that prevent oxygen leakage from the
cylinder by releasing gas only when the patient inhales, as
opposed to releasing gas constantly, which necessitates
more-frequent cylinder replacement. Large stationary
and small portable gas cylinders can be used in the hos-
pital or the home. Oxygen also can be stored as a highly
concentrated liquid. Oxygen turns to liquid only when it is
kept at very cold temperatures. When it is released under
pressure from cold storage, it is converted to a gas. Liquid
oxygen can be stored in small or large insulated containers,
which can be refilled at pharmacies or by delivery services.
Oxygen is usually administered in controlled amounts
per minute, a measure known as the flow rate. Flow rate is
determined based on measurements of a patient’s blood
oxygen levels. Two tests that are commonly used to assess
the concentration of oxygen in the blood include the arte-
rial blood gas (ABG) test and the pulse oximetry test. In
the ABG test, blood is drawn from an artery, and blood
acidity, oxygen, and carbon dioxide levels are measured. In
pulse oximetry, a probe, generally placed over the end of a
finger, is used to indirectly determine hemoglobin satura-
tion—the percent of hemoglobin molecules in the blood
216
that are carrying oxygen. The device uses light-emitting

diodes and a photodetector to measure light absorption in
the capillaries. The difference between absorption read-
ings during systole (when the heart contracts) and during
diastole (when the heart relaxes) are used to calculate
hemoglobin saturation.
If oxygen flow rate is too low, the patient will not
receive enough oxygen and could be at risk of injury from
severe hypoxemia, which can lead to tissue dysfunction
and cell death. Likewise, adverse physiological effects may
ensue if the flow rate is too high. For example, premature
infants who receive excessive amounts of oxygen in their
first days of life may develop a blinding disorder known as
retinopathy of prematurity. Excess oxygen flow also can
result in conditions such as barotrauma. For example,
HBOT is associated with an increased risk of barotrauma
of the ear. Bronchopulmonary dysplasia, a chronic disor-
der affecting infants, is characterized by absent or
abnormal repair of lung tissue following high-pressure or
excessive oxygen administration. Oxygen therapy is con-
traindicated in patients undergoing treatment with
certain forms of chemotherapy, such as with the drug
bleomycin. Bleomycin damages cancer cells by stimulat-
ing the production of reactive oxygen species, a response
that is amplified in the presence of excess oxygen, leading
to the damage of healthy tissues.
In general, the use of home oxygen therapy can reduce
hospital admission and extend survival in patients with
diseases such as COPD. However, oxygen therapy does
not alter the progression of lung disease. Also, because
patients need to use oxygen for a significant portion of
each day and because it can lead to additional difficulties
in mobility, it does not appeal to some patients.
Compressed-gas cylinders present a significant safety haz-
ard in the home as well; if they are not secured and stored
217
properly, they may cause explosions. Likewise, oxygen can

readily spread fire, and thus there is a significant safety
hazard associated with the use of oxygen in the presence
of pilot lights, candles, or other sources of ignition.
Furthermore, the prescription of oxygen for patients who
smoke or who share a household with smokers is consid-
ered controversial.
Artificial Respiration
Artificial respiration is breathing induced by some manip-
ulative technique when natural respiration has ceased or is
faltering. Such techniques, if applied quickly and properly,
can prevent some deaths from drowning, choking, stran-
gulation, suffocation, carbon monoxide poisoning, and
electric shock. Resuscitation by inducing artificial respira-
tion consists chiefly of two actions:
1. establishing and maintaining an open air pas-

sage from the upper respiratory tract (mouth,
throat, and pharynx) to the lungs and
2. exchanging air and carbon dioxide in the termi-
nal air sacs of the lungs while the heart is still
functioning. To be successful such efforts must
be started as soon as possible and continued
until the victim is again breathing.
The most widely used method of inducing artificial

respiration is mouth-to-mouth breathing, which has been
found to be more effective than the manual methods used
in the past. The person using mouth-to-mouth breathing
places the victim on his back, clears his mouth of foreign
material and mucus, lifts the lower jaw forward and upward
to open the air passage, places his own mouth over the vic-
tim’s mouth in such a way as to establish a leak-proof seal,
218
Mouth-to-mouth breathing is the most effective means of manual artificial

respiration. Stockbyte/Getty Images
219
and clamps the nostrils. He then alternately breathes into

the victim’s mouth and lifts his own mouth away, permit-
ting the victim to exhale. If the victim is a child, the rescuer
may cover both the victim’s mouth and nose. The rescuer
breathes 12 times each minute (15 times for a child and 20
for an infant) into the victim’s mouth.
Thoracentesis
Thoracentesis is a medical procedure used in the diagnosis
and treatment of conditions affecting the pleural space. It
is most often used to diagnose the cause of pleural effusion,
the abnormal accumulation of fluid in the pleural space.
Pleural effusion can result in difficulty in breathing and
often occurs secondary to conditions that affect the heart
or lungs, including heart failure, tumours, and lung infec-
tions, such as tuberculosis and pneumonia. Thoracentesis
is used therapeutically to relieve the symptoms associated
with pleural effusion, as well as to prevent further com-
plications associated with the condition, including pleural
empyema.
Prior to thoracentesis, the results of chest percussion
and imaging tests, such as chest X-rays or computerized
axial tomography chest scans, are assessed to precisely
locate the site of fluid accumulation and to evaluate the
volume of fluid present. In the subsequent thoracentesis
procedure, a needle is inserted through the chest wall and
into the effusion site in the pleural space. Needle place-
ment is sometimes guided by ultrasound to avoid
puncturing nearby tissues, including the lungs, liver, and
spleen. Once the needle is inserted, fluid is drawn out of
the pleural cavity using a syringe or other aspiration tech-
nique. For diagnostic applications, a small amount of fluid
is drawn and then analyzed for the presence of a variety of
substances, including infectious organisms, particles such
220
as asbestos, and tumour cells. The results of these analyses

frequently warrant further diagnostic testing, particularly
upon detection of cancerous cells, which are suggestive of
mesothelioma or lung cancer.
Thoracentesis is a relatively quick procedure, generally
lasting about 10 to 15 minutes. However, for several hours
afterward patients are often observed for the manifesta-
tion of adverse effects. Minor complications associated
with thoracentesis include pain and cough. More serious
complications include pneumothorax, the accumulation
of air in the pleural space, which occurs when a needle
punctures the lungs; and aberrant stimulation of the
vasovagal reaction, a reflex of the nervous system that
causes heart rate to slow (bradycardia) and blood ves-
sels in the lower extremities to dilate, leading to a drop
in blood pressure and fainting (syncope). Thoracentesis is
contraindicated in persons with bleeding disorders (i.e.,
coagulopathy).
Hyperbaric Chamber
A hyperbaric chamber, also known as a decompression
chamber (or recompression chamber), is a sealed chamber
in which a high-pressure environment is used primarily to
treat decompression sickness, gas embolism, carbon mon-
oxide poisoning, gas gangrene resulting from infection by
anaerobic bacteria, tissue injury arising from radiation
therapy for cancer, and wounds that are difficult to heal.
Experimental compression chambers first came into
use around 1860. In its simplest form, the hyperbaric
chamber is a cylindrical metal or acrylic tube large enough
to hold one or more persons and equipped with an access
hatch that retains its seal under high pressure. Air, another
breathing mixture, or oxygen is pumped in by a compres-
sor or allowed to enter from pressurized tanks. Pressures
221
A hyperbaric chamber creates a high-pressure environment, which increases

oxygen availability to the body in therapeutic treatment. Chris McGrath/
Getty Images
used for medical treatment are usually 1.5 to 3 times higher

than ordinary atmospheric pressure.
The therapeutic benefits of a high-pressure environ-
ment derive from its direct compressive effects, from
the increased availability of oxygen to the body (because
of an increase in the partial pressure of oxygen), or from a
combination of the two. In the treatment of decompres-
sion sickness, for example, a major effect of the elevated
pressure is shrinkage in the size of the gas bubbles that
have formed in the tissues. In the treatment of carbon
monoxide poisoning, the increased oxygen speeds clear-
ance of carbon monoxide from the blood and reduces
damage done to cells and tissues.
222
Lung Transplantation
Early attempts at transplanting a single lung in patients

with severe bilateral lung disease were not successful, but
from the late 1970s bilateral lung transplantation had
some striking results. Persons severely disabled by cystic
fibrosis, emphysema, sarcoidosis, pulmonary fibrosis, or
severe primary pulmonary hypertension can achieve
nearly normal lung function several months after the pro-
cedure. Because transplantation offers the only hope for
persons with severe lung disease, who may be relatively
young, the techniques are being pursued aggressively in
specialized centres. Availability of donor lungs is sharply
limited by the number of suitable donors; for example,
many people who die of severe head injuries, which pre-
sumably would leave the lungs intact, often have also
suffered lung injury or lung infection. With proper selec-
tion of donor organs and proper transplantation technique,
survival at one year has been reported at 90 percent.
Many recipients of single or double lung trans-
plantation develop bronchiolitis obliterans beginning
several months or years after surgery. This complication
is thought to represent gradual immunologic rejection of
the transplanted tissue despite the use of immunosuppres-
sant drugs. Brochiolitis obliterans and the constant risk of
serious infection brought about by the use of immunosup-
pressant drugs limit survival to approximately 40 to 60
percent five years after surgery.
Conclusion
In the 21st century, respiratory medicine has continued to
fulfill a vital role in advancing scientists’ understanding of
respiratory disease and of the basic cellular and molecular
processes that contribute to the normal function of the
223
respiratory system. The negative influence of behaviours

such as tobacco smoking on lung function is now well doc-
umented, and this understanding has contributed to a
more complete realization of the importance of preven-
tion and early detection of diseases such as lung cancer. In
fact, with health and environmental concerns at the fore-
front, countries worldwide have initiated national and
international programs aimed at reducing human expo-
sure to pollutants. In many countries, these efforts have
led to smoking bans in public areas and to governmental
regulations limiting occupational exposure to irritants.
Such progress promises to reduce the global mortality of
lung cancer, mesothelioma, and similar preventable respi-
ratory afflictions.
Significant advances also have occurred concerning
scientists’ understanding of the genetic causes of respira-
tory disorders and of the agents responsible for infectious
respiratory diseases. For decades, basic knowledge of the
viruses that cause the common cold eluded scientists.
However, in 2009 researchers reported having mapped
the genetic codes of rhinoviruses, which are the most fre-
quent cause of the common cold. The genetic information
was being used to establish an understanding of the
relationships between the dozens of common-cold rhino-
viruses and was expected to provide new insights that
could potentially lead to the development of diagnostic
tests and possibly even new drugs or vaccines. The impor-
tance of understanding the evolutionary patterns of
respiratory viruses is perhaps best illustrated by the vari-
ous types of influenza virus. Influenza viruses circulate
globally, acquiring genetic mutations that alter their infec-
tious characteristics, sometimes drastically increasing
their ability to infect and cause disease in humans. The
influenza virus that produced the H1N1 pandemic of 2009
is at the centre of these ongoing investigations.
224
Another important factor behind the advance of respi-

ratory medicine has been the elucidation of cellular
processes that underlie respiratory disease. For example,
discoveries of cellular proteins that are involved in cancer
and that facilitate the transport of infectious agents into
cells have spurred the development of drugs designed to
inhibit these pathological activities. In addition, the iden-
tification of disease-associated metabolic changes within
cells and tissues has played an important role in the devel-
opment of various functional and diagnostic tests, such as
the arterial blood gas test to determine blood oxygen lev-
els in persons suffering from chronic respiratory disease.
As researchers and physicians continue to uncover new
information about the human respiratory system, these
tests are likely to undergo a series of refinements and to be
augmented by the development of new tests, as well as
new treatments.
225
GLOSSARY
apnea Cessation of breathing.
convection The transfer of heat by movement of a
heated fluid such as air or water.
cricoid A large cartilaginous piece of the laryngeal skel-
eton with a signet-ring shape.
diffusion Primary mode of transport of gases between
air and blood in the lungs and between blood and
respiring tissues in the body.
epiglottis Cartilaginous, leaf-shaped flap; functions as a
lid to the larynx and, during the act of swallowing,
controls the traffic of air and food.
extrinsic muscles Join the laryngeal skeleton cranially
to the hyoid bone or to the pharynx and caudally to
the sternum. Act on the larynx as a whole, moving it
upward or downward.
glottis A sagittal slit formed by the vocal cords.
glycolysis Fermentation, or transformation of glucose
into energy.
hyperbaric chamber A sealed chamber in which a high-
pressure environment is used for medical treatment.
Also known as a decompression chamber or recom-
pression chamber.
hypercapnia Excess carbon dioxide retention.
hyperventilation Form of overbreathing that
increases the amount of air entering the pulmonary
alveoli.
hypoventilation When the quantity of inspired air
entering the lungs is less than is needed to maintain
normal exchange.
226
7 Glossary 7
hypoxia Reduction of oxygen supply to tissues to less

than physiological levels.
intrinsic muscles Attach to the skeletal components of
the larynx and act directly or indirectly on the shape,
length, and tension of the vocal cords.
larynx A complex organ that serves as an air canal to the
lungs and a controller of its access, and as the organ of
phonation.
metastasis Migration and spread of cancerous cells
from a tumour to distant sites in the body, resulting in
the development of secondary tumours.
nasopharynx Primarily a passageway for air and secre-
tions from the nose to the oral pharynx.
neuraminidase A glycoprotein on the surface of influ-
enza viruses.
paranasal sinuses Cavities in the bones that adjoin the nose.
pharyngitis Painful inflammatory illness of the passage
from the mouth to the pharynx or of the pharynx itself.
pleura In humans, a thin membranous sac encasing
each lung.
pleural effusion Accumulation of watery fluid between
the membrane lining the thoracic cage and the mem-
brane covering the lung.
purulent Pus-producing.
rhinitis Inflammation of the mucous tissue of the nose.
sinusitis Acute or chronic inflammation of the mucosal
lining of one or more paranasal sinuses.
surfactant Substance that, when added to a liquid,
reduces its surface tension, thereby increasing its
spreading and wetting properties.
thrombus Clot that forms in the blood vessel and
remains at the point where it was formed.
227
BIBLIOGRAPHY
Basic information about the respiratory system and the
process of respiration is included in Andrew Davies and
Carl Moores, The Respiratory System (2003); and Michael P.
Hlastala and Albert J. Berger, Physiology of Respiration, 2nd.
ed. (2001). Comprehensive coverage of the diseases of the
human respiratory system is provided by Alfred P. Fishman
and Jack A. Elias, Fishman’s Pulmonary Diseases and Disorders,
4th ed. (2008).
Control of breathing is described in Murray D. Altose
and Yoshikazu Kawakami (eds.), Control of Breathing in
Health and Disease (1999); and Jerome A. Dempsey and
Allan I. Pack (eds.), Regulation of Breathing, 2nd ed. (1995).
Abnormal breathing during sleep is covered by Nicholas
A. Saunders and Colin E. Sullivan (eds.), Sleep and Breathing,
2nd ed. (1994).
Adaptations of the human respiratory system to high
altitude are described in a comprehensive but readable
manner in Donald Heath and David Reid Williams, High-
Altitude Medicine and Pathology, 4th ed. (1995).
The effects of swimming and diving on respiration are
detailed in Peter B. Bennett and David H. Elliott (eds.),
The Physiology and Medicine of Diving, 4th ed. (1993).
The human respiratory system is described in David
V. Bates, Peter T. Macklem, and Ronald V. Christie,
Respiratory Function in Disease: An Introduction to the
Integrated Study of the Lung, 2nd ed. (1971), a detailed text
on impairment of lung function caused by disease; and
Robert G. Fraser et al., Diagnosis of Diseases of the Chest,
2nd ed., 4 vol. (1977–79), with vol. 1 also available in a
3rd ed. (1988). H. Corwin Hinshaw and John F. Murray,
228
7 Bibliography 7
Diseases of the Chest, 4th ed. (1980), is a general textbook

covering diagnosis and treatment of chest diseases;
see also J. G. Scadding and Gordon Cumming (eds.),
Scientific Foundations of Respiratory Medicine (1981). Steven
E. Weinberger, Principles of Pulmonary Medicine, 3rd
ed. (1998), is an introductory text in which respiratory
pathophysiology is considered from the clinical vantage.
Comprehensive texts include Gordon Cumming and
Stephen J. Semple, Disorders of the Respiratory System, 2nd
ed. (1980); John Crofton and Andrew Douglas, Respiratory
Diseases, 3rd ed. (1981); and Ian R. Cameron and Nigel T.
Bateman, Respiratory Disorders (1983). Alfred P. Fishman
(ed.), Pulmonary Diseases and Disorders, 2nd ed., 3 vol.
(1988), provides a comprehensive overview of patho-
physiology as related to clinical syndromes. See also John
F. Murray and Jay A. Nadel (eds.), Textbook of Respiratory
Medicine, 2nd ed. (1994); and Andrew M. Churg et al.
(eds.), Thurlbeck’s Pathology of the Lung, 3rd ed. (2005).
229
INDEX
A asthma, 42, 160–164, 169, 175,
182, 184, 197, 198, 213
acid–base balance, 51, 52, 75 atelectasis, 141–144
acidosis, 184
Actinomyces, 111
Adam’s apple, 27 B
adenosine triphosphate (ATP), barotrauma, 86, 189–192, 217
73, 74, 75, 77 Bert, Paul, 188
Agricola, Georgius, 171 bird fancier’s lung, 166
AIDS, 111, 112–113, 115, 117, black lung, 170–171
118–119 Bordet, Jules, 106
air–blood barrier, 30, 35, 39 bradykinin, 50
alcoholism, 96, 97, 113 Breuer, Josef, 49
alkalosis, 184–186 bronchi, structure and function
altitude sickness, 159, 188–189 of, 30, 33–34
alveoli, structure of, 34–35 stem, structure of, 28–29
amantadine, 103 bronchiectasis,130–131, 198
anemia, 64, 186, 187 bronchioles, structure and
anesthesia, 46, 152, 208, 209 function of, 30, 33–34
animals, 76, 79–80, 81, 193 bronchiolitis, 100–102, 136,
anthracosis, 171 152, 223
antibiotics, 91, 92, 93, 94, 107, bronchitis, 99–100, 102, 103,
108, 109, 110, 114, 116, 129, 131–133, 134, 135, 137, 168, 169,
131, 137, 147, 164, 196, 210, 171, 175, 181, 197
211, 214 bronchopulmonary dysplasia, 217
antihistamines, 211, 212–214 bronchoscopy, 205–208
aortic body, 48 brown lung, 174
apnea, 46, 52, 122, 124–125, 126 Buerger disease, 187
arterial gas embolism, 85 byssinosis, 174–175
artificial respiration, 218–220
asbestos, 127, 153, 159, 168–169,
171–173, 176, 221 C
asbestosis, 171–173 cancer, 81, 111, 123, 127, 169
asphyxiation, 194 lung, 38, 152–156, 169, 172, 173,
230
7 Index 7
181, 182, 198, 199, 204, E

209, 221
emphysema, 85, 102, 122, 127–129,
cardiopulmonary resuscitation
130, 132, 133–136, 137, 156–158,
(CPR), 129, 215
168, 170, 171, 175, 184, 190,
carotid body, 47, 48, 80, 81
197, 220, 223
central nervous system disease, 52
eosinophilic granuloma, 149, 150
Cheyne-Stokes breathing, 52
epiglottis, 25, 27, 96, 98–99
chloride shift, 67
epiglottitis, 98–99
chronic obstructive pulmonary
epinephrine, 98, 212
disease (COPD), 130,
exercise (training), 46, 50, 51–52,
136–138, 215, 217
62, 64, 75–78, 84, 135, 137, 147,
Clara cells, 30, 34
158, 174, 183, 201
cold, common, 87, 88–91, 93, 94,
95, 98, 106, 213
cause of, 88 F
corticosteroids, 98, 138, farmer’s lung, 166
161, 164 fungi, 91, 94, 108, 111, 112, 182
coughing
blood, 117, 137, 145, 197, 207
physiology of, 50, 58–59, 132 G
types of, 105–106, 192, gas exchange, abnormal, 69–72
196–197, 198 Gengou, Octave, 106
croup, 87, 98–99 glycolysis, 74
cystic fibrosis, 122, 130, 131, goblet cells, 30
145–148, 210, 223 Goodpasture syndrome, 151
D H
decompression sickness, 86, 159, Haldane, John Scott, 183
189–192, 215, 221, 222 hay fever, 164, 211, 213
decongestants, 196, 211–212 hemoglobin, 47, 63, 64, 65, 66, 67,
diaphragm, 21, 25, 44, 56, 122, 143, 75, 78, 80, 81, 136, 183, 186,
144, 156, 158 187, 201, 216–217
diffusion limitation, 69, 72 Hering, Ewald, 49
diphtheria, 92, 95, 97, 106, 214 Hering-Breuer reflex, 49
diving, 60, 78, 81–86, 157–158, 177, high altitudes, 47, 65, 79–81, 187,
190, 191–193 188–189, 190
drowning, 159, 180, 193–195, 218 histamine, 50, 160
dyspnea, 84, 197–198 HIV, 115, 119
231
hookworm, 163 cancer of, 38, 152–156, 169, 172,

hydrothorax, 127 173, 181, 182, 198, 199, 204,
hygiene, 114–115, 119 209, 221
hyperbaric chamber, 215, 221–222 collapse of, 55–56, 70, 127, 129,
hypercapnia, 83 141, 143, 159
hypersensitivity pneumonitis, congestion of, 138–141,
166–167 178, 197
hyperventilation, 81–82, 184–186 development of, 38–40
hypothyroidism, 125 infarction, 144–145, 177
hypoventilation, 69, 126 size of, 31
hypoxemia, 135–136, 149, 215, 217 transplantation of, 138, 147,
hypoxia, 46–48, 52, 83, 186–188 149, 173, 178, 223
lung ventilation/perfusion scan,
204–205
I
idiopathic pulmonary fibrosis, 149
influenza, 88, 91, 93, 96, 98, 99, M
102–105, 110, 114, 138, 139, measles, 99
167, 199 mediastinoscopy, 208–209
bird flu, 103 mediastinum, 26, 31, 37, 122,
H1N1, 104 156–158, 190, 208
vaccine, 103, 173 medulla, 41, 44, 45, 49, 50
meningitis, 92, 117
mesothelioma, 127, 128, 171–173,
K 176, 198, 221
kidney, 94, 117, 150, 151, 184 metabolism, 47, 50, 51–52, 68,
73–78, 81
aerobic, 74, 76–77, 78
L anaerobic, 74, 76
Laënnec, René-Théophile- Monge disease, 81
Hyacinthe, 196 mountain sickness, 81
laryngitis, 87, 95–96 mucoviscidosis, 145
larynx, structure and function of,
26–28
Legionnaire disease, 87, 110,
N
113–114, 214 nephritis, 94
leukemia, 100 nerves
lungs laryngeal, 26
232
7 Index 7
olfactory, 23–24 128, 129–130, 136, 208,

sinus, 47 209, 221
vagus, 38, 45, 50 pollution, 131, 137, 180–182
nitrogen narcosis, 85 pons, 41, 44
nose Pontiac fever, 114
cilia, 93 Pott disease, 118
congestion of, 91, 164 prostaglandins, 50
inflammation of, 89 psittacosis, 107–108, 110
structure and function of, pulmonary alveolar proteinosis,
21–24, 99 150–151
pulmonary edema, 36, 84, 139,
141, 178, 189, 194
O
pulmonary parenchyma, 34
obesity, 53, 124, 125, 126 pyothorax, 128
oseltamivir, 103, 104
osteoporosis, 137
oxygen therapy, 214–218 R
Relenza, 103, 104–105
P respiratory distress syndrome,
159, 179–180
parasites, 91, 107, 108, 111
Reynaud disease, 187
parrot fever, 107
rheumatic fever, 91, 94, 179
penicillin, 92, 93, 108, 211, 214
rheumatoid arthritis, 100
pertussis, 105–106, 107, 164
rhinoviruses, 88
pharyngitis, 87, 91–92, 214
rimantadine, 103
pharynx, structure and function
Röntgen,Wilhelm Conrad, 203
of, 24–25
pickwickian syndrome, 126
pleura, 26, 31–32, 57, 122, 126–130,
154, 172, 198 S
pleural effusion, 126, 127–129, sarcoidosis, 149–150, 208, 223
152, 198, 200, 220 scarlet fever, 95
pleurisy, 33, 113, 117, 126, 127, 198 shunting, 69–71
pneumoconiosis, 168–169, 170 silicosis, 169–170
pneumonia, 87, 95, 103, 106, sinuses, 19, 22, 88, 92, 122
108–113, 114, 128, 130, 138, function of, 22
139, 146, 155, 167, 170, 173, irrigation of, 93
180, 184, 198, 211, 214, 220 sinusitis, 87, 92–94, 160
pneumothorax, 33, 56, 85, 127, sleep, 50, 52–53, 136
233
smallpox, 97 trachea, structure and function

smell, 21, 23–24, 94 of, 28–30
smoking, 95, 97, 102, 122, 123, 130, tracheitis, 87, 96–98
131–132, 133–135, 137, 138, 150, trench mouth, 95
153, 163, 171, 172, 175, 176, 182, tuberculosis, 87, 92, 95, 97, 111,
183, 218 114–121, 128, 164, 170, 171,
sneezing,102, 106, 116, 164 197, 199, 204, 208, 220
snoring, 53, 123–124 typhoid, 97
sore throat, 91, 92, 94
staphylococci, 97, 110, 146
strep throat, 92 V
streptococcal bacteria, 91, 92, 93, vaccination, 103, 107, 119, 138,
96, 97, 99, 108, 109, 214 164, 173
surgery, 33, 56, 93, 94, 95, 122, 125, Valsalva maneuver, 58
129, 130, 136, 138, 143, 152, ventilation–blood flow
155–156, 178, 198, 199, 209 imbalance, 69
swimming, 78, 81–86 vestibular folds, 27–28
syphilis, 92, 96, 97 vitamin C, 91
vocal chords, false, 27–28
T
Tamiflu, 103, 104
W
tetanus, 106
thoracentesis, 220–221 whooping cough, 99, 105–107
thoracic emphyema, 127–129
thoracic squeeze, 192–193
tonsillitis, 87, 94–95 Z
tonsils, 25, 53, 88, 91, 92, 94–95, zanamivir, 103, 104–105
118, 124
234

Basic Sciences-The Human Body - The Respiratory

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Basic Sciences-The Human Body - The Respiratory

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Published in 2011 by Britannica Educational Publishing

(a trademark of Encyclopædia Britannica, Inc.)

Copyright © 2011 Encyclopædia Britannica, Inc. Britannica, Encyclopædia Britannica,

Distributed exclusively by Rosen Educational Services.

Britannica Educational Publishing

Rosen Educational Services

Library of Congress Cataloging-in-Publication Data

The respiratory system / edited by Kara Rogers.

Manufactured in the United States of America

Chapter 1: Anatomy and

Chapter 2: Control and

Chapter 3: Gas Exchange and

Chapter 4: Infectious Diseases

T he human lungs are amazing feats of nature. They

bronchioles, which range in diameter from 3 mm (0.12

abdomen. One of the major abdominal muscles involved

diaphragm is the major muscle that facilitates breathing,

sleep at night. This enables the body to adjust to the

tuberculosis bacteria spread slowly in the lungs and cause

variety of factors, although tobacco smoking is the pri-

Lung cancer treatments may consist of surgery, che-

the design of the

protected by the bony and muscular thoracic cage. The

which connect the gas–exchange region inside the body

septum. Each canal opens to the face by a nostril and into

Sagittal view of the human nasal cavity. Encyclopædia Britannica, Inc.

reflects the particular ancillary functions of the nose and

olfactory cells through the bony roof of the nasal cavity to

Sagittal section of the pharynx. Encyclopædia Britannica, Inc.

nasopharynx is located a lymphatic organ, the pharyngeal

anteriorly in the midline. At the upper end of the fusion

of a fibroelastic membrane. Between the vestibular folds

The Trachea and the Stem Bronchi

this arrangement is that foreign bodies passing beyond

Structural design of the

The conducting airways comprise the trachea, the two

proper is missing, and the airway consists of alveolar ducts.

Anatomy of the human lungs. Encyclopædia Britannica, Inc.

of the thoracic cavities and the lung surface, respectively,

the lungs to move smoothly along the walls of the cavity

The Bronchi and Bronchioles

small conducting airways ranging in diameter from three

The Gas-Exchange Region

diameter of about 250 to 300 micrometres, and open on

fluid. The connective tissue comprises a system of fibres,

Blood Vessels, Lymphatic Vessels, and Nerves

venules and drained into small veins. These do not accom-

paths from the lung are complex. The precise knowledge

are of endodermal origin), and the surrounding tissues and

The newborn lung is far from being a miniaturized

T he respiratory system is intimately associated with

swings in carbon dioxide production and oxygen con-

Singing demands a strong diaphragm to control breath. Shutterstock.com

influenced by higher brain centres and even controlled vol-

abruptly. After a gap of a few milliseconds, inspiratory

and the abdominal muscles may be active even during quiet

trip to high altitudes), stimulates the carotid and aortic

intestinal peptide, and substance P, are located within the

medulla. The same areas of the ventral medulla also con-

Muscle and Lung Receptors

which send signals to the medulla by the vagus nerve,

One of the remarkable features of the respiratory control

Mechanoreceptors, arterial chemoreceptors, and thermal receptors all work in