Introduction to Respiratory System Infections
Introduction to Respiratory System Infections
The respiratory tract is one of the main portals of entry into the
human body for microbial pathogens. On average, a human
takes about 20,000 breaths each day. This roughly corresponds
to 10,000 liters, or 10 cubic meters, of air. Suspended within
this volume of air are millions of microbes of terrestrial, animal,
and human origin—including many potential pathogens. A few
of these pathogens will cause relatively mild infections like sore
throats and colds. Others, however, are less benign. According
to the World Health Organization, respiratory tract infections
such as tuberculosis, influenza, and pneumonia were
responsible for more than 4 million deaths worldwide in 2012.[1]
At one time, it was thought that antimicrobial drugs and
preventive vaccines might hold respiratory infections in check
in the developed world, but recent developments suggest
otherwise. The rise of multiple-antibiotic resistance in
organisms like Mycobacterium tuberculosis has rendered many of
our modern drugs ineffective. In addition, there has been a
recent resurgence in diseases like whooping cough and
measles, once-common childhood illnesses made rare by
effective vaccines. Despite advances in medicine and public
health programs, it is likely that respiratory pathogens will
remain formidable adversaries for the foreseeable future.
Anatomy and Normal Microbiota of the
Respiratory Tract
The primary function of the respiratory tract is to exchange
gases (oxygen and carbon dioxide) for metabolism. However,
inhalation and exhalation (particularly when forceful) can also
serve as a vehicle of transmission for pathogens between
individuals.
Anatomy of the Upper Respiratory System
The respiratory system can be conceptually divided into upper
and lower regions at the point of the epiglottis, the structure
that seals off the lower respiratory system from the pharynx
during swallowing (Figure 1). The upper respiratory system is in
direct contact with the external environment. The nares (or
nostrils) are the external openings of the nose that lead back
into the nasal cavity, a large air-filled space behind the nares.
,These anatomical sites constitute the primary opening and first
section of the respiratory tract, respectively. The nasal cavity is
lined with hairs that trap large particles, like dust and pollen,
and prevent their access to deeper tissues. The nasal cavity is
also lined with a mucous membrane and Bowman’s glands that
produce mucus
to help trap particles and microorganisms for removal. The
nasal cavity is connected to several other air-filled spaces. The
sinuses, a set of four, paired small cavities in the skull,
communicate with the nasal cavity through a series of small
openings.
The nasopharynx is part of the upper throat extending from the
posterior nasal cavity. The nasopharynx carries air inhaled
through the nose. The middle ear is connected to the
nasopharynx through the eustachian tube. The middle ear is
separated from the outer ear by the tympanic membrane, or ear
drum. And finally, the lacrimal glands drain to the nasal cavity
through the nasolacrimal ducts (tear ducts). The open
connections between these sites allow microorganisms to move
from the nasal cavity to the sinuses, middle ears (and back),
and down into the lower respiratory tract from the
nasopharynx.
The oral cavity is a secondary opening for the respiratory tract.
The oral and nasal cavities connect through the fauces to the
pharynx, or throat. The pharynx can be divided into three
regions: the nasopharynx, the oropharynx, and the
laryngopharynx. Air inhaled through the mouth does not pass
through the nasopharynx; it proceeds first through the
oropharynx and then through the laryngopharynx. The palatine
tonsils, which consist of lymphoid tissue, are located within the
oropharynx. The laryngopharynx, the last portion of the
pharynx, connects to the larynx, which contains the vocal fold
(Figure 1).
Anatomy of the Lower Respiratory System
The lower respiratory system begins below the epiglottis in the
larynx or voice box (Figure 2). The trachea, or windpipe, is a
cartilaginous tube extending from the larynx that provides an
unobstructed path for air to reach the lungs. The trachea
bifurcates into the left and right bronchi as it reaches the lungs.
These paths branch repeatedly to form smaller and more
extensive networks of tubes, the bronchioles. The terminal
bronchioles formed in this tree-like network end in cul-de-sacs
called the alveoli. These structures are surrounded by capillary
,networks and are the site of gas exchange in the respiratory
system. Human lungs contain on the order of 400,000,000
alveoli. The outer surface of the lungs is protected with a
double-layered pleural membrane. This structure protects the
lungs and provides lubrication to permit the lungs to move
easily during respiration.
Defenses of the Respiratory System
The inner lining of the respiratory system consists of mucous
membranes (Figure 3) and is protected by multiple immune
defenses. The goblet cells within the respiratory epithelium
secrete a layer of sticky mucus. The viscosity and acidity of
this secretion
inhibits microbial attachment to the underlying cells. In
addition, the respiratory tract contains ciliated epithelial
cells. The beating cilia dislodge and propel the mucus, and
any trapped microbes, upward to the epiglottis, where they
will be swallowed.
Elimination of microbes in this manner is referred to as the mucociliary
escalator effect and is an important mechanism that prevents
inhaled microorganisms from migrating further into the lower
respiratory tract.
The upper respiratory system is under constant surveillance by
mucosa-associated lymphoid tissue (MALT), including the
adenoids and tonsils. Other mucosal defenses include secreted
antibodies (IgA), lysozyme, surfactant, and antimicrobial
peptides called defensins. Meanwhile, the lower respiratory
tract is protected by
alveolar macrophages. These phagocytes efficiently kill any
microbes that manage to evade the other defenses. The
combined action of these factors renders the lower respiratory
tract nearly devoid of colonized microbes.
Normal Microbiota of the Respiratory System
The upper respiratory tract contains an abundant and
diverse microbiota. The nasal passages and sinuses are
primarily colonized by members of
the Firmicutes, Actinobacteria, and Proteobacteria. The most
common bacteria identified include Staphylococcus
epidermidis, viridans group
, streptococci (VGS), Corynebacterium spp. (diphtheroids),
Propionibacterium spp., and Haemophilus spp. The oropharynx
includes many of the same isolates as the nose and sinuses,
with the addition of variable numbers of bacteria like species
of Prevotella, Fusobacterium, Moraxella, and Eikenella, as well as
some Candida fungal isolates. In addition, many healthy
humans asymptomatically carry potential pathogens in the
upper respiratory tract. As much as 20% of the population
carry Staphylococcus aureus in their nostrils.[1] The pharynx,
too, can be colonized with pathogenic strains of
Streptococcus, Haemophilus, and Neisseria.
The lower respiratory tract, by contrast, is scantily
populated with microbes. Of the organisms identified in
the lower respiratory tract, species
of Pseudomonas, Streptococcus, Prevotella, Fusobacterium, and
Veillonella are the most common. It is not clear at this time if
these small populations of bacteria constitute a normal
microbiota or if they are transients.
Many members of the respiratory system’s normal microbiota
are opportunistic pathogens. To proliferate and cause host
damage, they first must overcome the immune defenses of
respiratory tissues. Many mucosal pathogens produce virulence
factors such as adhesins that mediate attachment to host
epithelial cells, or polysaccharide capsules that allow microbes
to evade phagocytosis. The endotoxins of gram-negative
bacteria can stimulate a strong inflammatory response that
damages respiratory cells. Other pathogens produce exotoxins,
and still others have the ability to survive within the host cells.
Once an infection of the respiratory tract is established, it tends
to impair the mucociliary escalator, limiting the body’s ability to
expel the invading microbes, thus making it easier for
pathogens to multiply and spread.
Vaccines have been developed for many of the most serious
bacterial and viral pathogens. Several of the most important
respiratory pathogens and their vaccines, if available, are
summarized in Table 1. Components of these vaccines will be
explained later in the chapter.
Introduction to Respiratory System Infections
The respiratory tract is one of the main portals of entry into the
human body for microbial pathogens. On average, a human
takes about 20,000 breaths each day. This roughly corresponds
to 10,000 liters, or 10 cubic meters, of air. Suspended within
this volume of air are millions of microbes of terrestrial, animal,
and human origin—including many potential pathogens. A few
of these pathogens will cause relatively mild infections like sore
throats and colds. Others, however, are less benign. According
to the World Health Organization, respiratory tract infections
such as tuberculosis, influenza, and pneumonia were
responsible for more than 4 million deaths worldwide in 2012.[1]
At one time, it was thought that antimicrobial drugs and
preventive vaccines might hold respiratory infections in check
in the developed world, but recent developments suggest
otherwise. The rise of multiple-antibiotic resistance in
organisms like Mycobacterium tuberculosis has rendered many of
our modern drugs ineffective. In addition, there has been a
recent resurgence in diseases like whooping cough and
measles, once-common childhood illnesses made rare by
effective vaccines. Despite advances in medicine and public
health programs, it is likely that respiratory pathogens will
remain formidable adversaries for the foreseeable future.
Anatomy and Normal Microbiota of the
Respiratory Tract
The primary function of the respiratory tract is to exchange
gases (oxygen and carbon dioxide) for metabolism. However,
inhalation and exhalation (particularly when forceful) can also
serve as a vehicle of transmission for pathogens between
individuals.
Anatomy of the Upper Respiratory System
The respiratory system can be conceptually divided into upper
and lower regions at the point of the epiglottis, the structure
that seals off the lower respiratory system from the pharynx
during swallowing (Figure 1). The upper respiratory system is in
direct contact with the external environment. The nares (or
nostrils) are the external openings of the nose that lead back
into the nasal cavity, a large air-filled space behind the nares.
,These anatomical sites constitute the primary opening and first
section of the respiratory tract, respectively. The nasal cavity is
lined with hairs that trap large particles, like dust and pollen,
and prevent their access to deeper tissues. The nasal cavity is
also lined with a mucous membrane and Bowman’s glands that
produce mucus
to help trap particles and microorganisms for removal. The
nasal cavity is connected to several other air-filled spaces. The
sinuses, a set of four, paired small cavities in the skull,
communicate with the nasal cavity through a series of small
openings.
The nasopharynx is part of the upper throat extending from the
posterior nasal cavity. The nasopharynx carries air inhaled
through the nose. The middle ear is connected to the
nasopharynx through the eustachian tube. The middle ear is
separated from the outer ear by the tympanic membrane, or ear
drum. And finally, the lacrimal glands drain to the nasal cavity
through the nasolacrimal ducts (tear ducts). The open
connections between these sites allow microorganisms to move
from the nasal cavity to the sinuses, middle ears (and back),
and down into the lower respiratory tract from the
nasopharynx.
The oral cavity is a secondary opening for the respiratory tract.
The oral and nasal cavities connect through the fauces to the
pharynx, or throat. The pharynx can be divided into three
regions: the nasopharynx, the oropharynx, and the
laryngopharynx. Air inhaled through the mouth does not pass
through the nasopharynx; it proceeds first through the
oropharynx and then through the laryngopharynx. The palatine
tonsils, which consist of lymphoid tissue, are located within the
oropharynx. The laryngopharynx, the last portion of the
pharynx, connects to the larynx, which contains the vocal fold
(Figure 1).
Anatomy of the Lower Respiratory System
The lower respiratory system begins below the epiglottis in the
larynx or voice box (Figure 2). The trachea, or windpipe, is a
cartilaginous tube extending from the larynx that provides an
unobstructed path for air to reach the lungs. The trachea
bifurcates into the left and right bronchi as it reaches the lungs.
These paths branch repeatedly to form smaller and more
extensive networks of tubes, the bronchioles. The terminal
bronchioles formed in this tree-like network end in cul-de-sacs
called the alveoli. These structures are surrounded by capillary
,networks and are the site of gas exchange in the respiratory
system. Human lungs contain on the order of 400,000,000
alveoli. The outer surface of the lungs is protected with a
double-layered pleural membrane. This structure protects the
lungs and provides lubrication to permit the lungs to move
easily during respiration.
Defenses of the Respiratory System
The inner lining of the respiratory system consists of mucous
membranes (Figure 3) and is protected by multiple immune
defenses. The goblet cells within the respiratory epithelium
secrete a layer of sticky mucus. The viscosity and acidity of
this secretion
inhibits microbial attachment to the underlying cells. In
addition, the respiratory tract contains ciliated epithelial
cells. The beating cilia dislodge and propel the mucus, and
any trapped microbes, upward to the epiglottis, where they
will be swallowed.
Elimination of microbes in this manner is referred to as the mucociliary
escalator effect and is an important mechanism that prevents
inhaled microorganisms from migrating further into the lower
respiratory tract.
The upper respiratory system is under constant surveillance by
mucosa-associated lymphoid tissue (MALT), including the
adenoids and tonsils. Other mucosal defenses include secreted
antibodies (IgA), lysozyme, surfactant, and antimicrobial
peptides called defensins. Meanwhile, the lower respiratory
tract is protected by
alveolar macrophages. These phagocytes efficiently kill any
microbes that manage to evade the other defenses. The
combined action of these factors renders the lower respiratory
tract nearly devoid of colonized microbes.
Normal Microbiota of the Respiratory System
The upper respiratory tract contains an abundant and
diverse microbiota. The nasal passages and sinuses are
primarily colonized by members of
the Firmicutes, Actinobacteria, and Proteobacteria. The most
common bacteria identified include Staphylococcus
epidermidis, viridans group
, streptococci (VGS), Corynebacterium spp. (diphtheroids),
Propionibacterium spp., and Haemophilus spp. The oropharynx
includes many of the same isolates as the nose and sinuses,
with the addition of variable numbers of bacteria like species
of Prevotella, Fusobacterium, Moraxella, and Eikenella, as well as
some Candida fungal isolates. In addition, many healthy
humans asymptomatically carry potential pathogens in the
upper respiratory tract. As much as 20% of the population
carry Staphylococcus aureus in their nostrils.[1] The pharynx,
too, can be colonized with pathogenic strains of
Streptococcus, Haemophilus, and Neisseria.
The lower respiratory tract, by contrast, is scantily
populated with microbes. Of the organisms identified in
the lower respiratory tract, species
of Pseudomonas, Streptococcus, Prevotella, Fusobacterium, and
Veillonella are the most common. It is not clear at this time if
these small populations of bacteria constitute a normal
microbiota or if they are transients.
Many members of the respiratory system’s normal microbiota
are opportunistic pathogens. To proliferate and cause host
damage, they first must overcome the immune defenses of
respiratory tissues. Many mucosal pathogens produce virulence
factors such as adhesins that mediate attachment to host
epithelial cells, or polysaccharide capsules that allow microbes
to evade phagocytosis. The endotoxins of gram-negative
bacteria can stimulate a strong inflammatory response that
damages respiratory cells. Other pathogens produce exotoxins,
and still others have the ability to survive within the host cells.
Once an infection of the respiratory tract is established, it tends
to impair the mucociliary escalator, limiting the body’s ability to
expel the invading microbes, thus making it easier for
pathogens to multiply and spread.
Vaccines have been developed for many of the most serious
bacterial and viral pathogens. Several of the most important
respiratory pathogens and their vaccines, if available, are
summarized in Table 1. Components of these vaccines will be
explained later in the chapter.
