Transcript RESPIRATORY TRACT DISEASES

RESPIRATORY TRACT
DISEASES
RESPIRATORY TRACT
DISEASES
• General Goal: To know the major mechanisms of defense in the URT,
the major mechanisms invaders use to avoid the defenses of the LRT,
the common modes of transmission and the most common microbes
that infect a particular location of the respiratory tract.
• Objectives:
• 1. defense mechanisms the body uses to protect itself from infections.
• 2. identify the microbes normally found in the respiratory tract (normal
flora).
• 4. the mechanisms microbes use to infect the respiratory tract.
• 5. The common microbial pathogens and the locations they usually
infect.
Respiratory Tract Pathogens Wide
Ranges of Organisms
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Viruses = Rhinoviruses, Respiratory syncitial virus (RSV),
Adenoviruses, Influenza, Parainfluenza
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Group A streptococci = pharyngitis
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Other streptococci = S. pneumoniae = sinusitis, Group B =
pneumonia of infants
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Other microorganisms = C. diphtheriae, M. pneumoniae, Fungi
Parasites
The respiratory tract is the most common site
for infection by pathogens.
• Direct contact with the physical environment and
is exposed to microorganisms in the air.
• The human respiratory tract is exposed to many
potential pathogens via the smoke, soot, and dust
that is inhaled from the air. It has been calculated
that the average individual ingests about 8
microorganisms per minute or 10,000 per day.
The anatomy of the respiratory tract –
elimination of particles and potential pathogens.
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Nasal cavity has a mucociliary lining.
The inside of the nose is lined with hair.
The turbinate bones ("baffle plates") are covered with mucus which collect particles not
filtered by nasal hairs.
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The adenoids and tonsils are lymphoid organs in the upper respiratory tract that are quite
important in developing an immune response to pathogens.
Mucus is secreted by both single and subepithelial mucus-secreting cells.
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There are two main obstacles a bacterium or virus must overcome in order to initiate an
infection in the respiratory tract.
1. The microorganism must avoid being caught up in the mucus layers of the upper
respiratory tract, being transported to the back of the throat, and eventually being
swallowed.
2. If the invader has avoided the physical defense mechanisms of the upper respiratory
tract, and is deposited in the lower respiratory tract or lung, it must either avoid
phagocytosis, or be able to survive and multiply in the phagocytic cell.
Normal Flora Organisms of the Nose,
Nasopharynx, and Oropharynx
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1. The most common bacteria found in the nose are staphylococci. These
organisms are found just inside the nares and include Staphylococcus
aureus and S. epidermidis.
2. In addition to the staphylococci, aerobic corynebacteria
("diphtheroids") can be cultured from the nasal surfaces.
3. Small numbers of Streptococcus pneumoniae, Neisseria meningitidis,
and Haemophilus influenzae can also be found in the nasopharynx.
However, most of these strains are not encapsulated or virulent. It
should be noted that nonencapsulated, nontypable H. influenzae has
been shown to play a significant role in the pathogenesis of otitis
media.
Normal Flora Organisms of the Nose,
Nasopharynx, and Oropharynx
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OROPHARINX
1. The nose and the oropharynx contains large numbers of S. aureus and
S. epidermidis.
1. The most important group of microorganisms native to this body niche
are the alpha-hemolytic streptococci or viridans streptococci: S. mitis,
S. mutans, S. milleri, and S. salivarius.
2. Additionally, cultures from this region usually show large numbers of
diphtheroids, Moraxella catarrhalis, and small Gram-negative cocci
related to Neisseria species.
Role of normal flora
The normal flora of these areas have two main functions that
play a role in maintaining the healthy state of the host.
1. The organisms compete with pathogenic organisms for
potential attachment sites.
1. These organisms often produce substances (toxins or acids)
which are bactericidal.
Mechanisms Used By Respiratory Tract
Pathogens To Initiate Disease
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ID - Sufficient number of infectious agent inhaled
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Airborne microbes.
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Alive and viable while in the air.
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The organism must be deposited on susceptible tissue in
the host.
Mechanisms Used By Respiratory Tract
Pathogens To Initiate Disease
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Colonize surfaces before it can cause obvious disease.
Mechanisms used especially by respiratory tract pathogens:
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Bacterial adherence factors = F and M proteins of Strep. pyogenes,
Hemagglutinins of B. pertussis.
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Extracellular toxins = diphtheria toxin; pertussis toxin.
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Growth in host tissue = viruses, chlamydia sp.
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Evasion of host immunity = capsules of Strep. pyogenes (also M
protein), S. pneumoniae and H. influenzae by inhibiting phagocytosis.
The Common Cold
ETIOLOGY
EPIDEMIOLOGY
• The common cold is caused by a multitude of organisms. 90 percent of
the cases of the common cold are due to viruses.
• The common cold is worldwide in it's distribution and is spread
person-to-person. Most commonly the viruses are spread during handto-hand contact (shaking hands, etc.). The average child (less than 5
years of age) will get 5-7 colds per year and the average adult will get
1-2 colds per year.
• The common cold is seen mostly in the winter months. More infections
in these months occur due to more person-to-person contact during this
time of year. The most common cause of the common cold is the
rhinoviruses (10 to 25%).
Nonbacterial Agents that Cause Upper Respiratory Tract
Infections of Man
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Myxoviruses
Influenza A, B, C
Parainfluenza 1, 2, 3, 4
Respiratory Syncytial Virus 1 (maybe 2)
Coronaviruses 1
Picornaviruses
Rhinoviruses- most common cause, > 100 types
Coxsackie virus A 24 (perhaps only A21 causes respiratory illnesses)
Coxsackie virus B 6 (perhaps only B4, B5 cause respiratory illnesses)
Echoviruses 31 (perhaps only types 11, 20, 25 cause respiratory illnesses)
Adenoviruses 34 (types 1, 2, 3, 5, 7, 14, 21 are responsible for respiratory illnesses)
Mycoplasma pneumoniae
Rhinoviruses
• These viruses are responsible for 25% of the colds
seen in the U.S. There are at least 100
immunologically distinct rhinoviruses. This makes
vaccine production virtually impossible. 80% of
these bind to ICAM-1on the human epithelial
cells. These viruses are picornaviruses labile to pH
of 3 therefore they are not present in the
gastrointestinal tract as one would see the
poliovirus. These viruses also grow optimally at
33° C which is the temperature of the nasal
mucosa of humans.
Coronaviruses
• These viruses are enveloped RNA viruses.
More than 20 strains of coronaviruses have
been obtained from humans. In adults
coronaviruses can cause from 10 to 24% of
common colds.
Coxsackieviruses and
Echoviruses
• Both these viruses are picornaviruses which are
placed in the enterovirus category due to their
residence in the intestines. Coxsackieviruses are
grouped into groups A and B. Each group consists
of several serotypes. Echoviruses are not grouped
but several types exist. Usually these viruses cause
aseptic meningitis and pleurodynia (pain in the
intercostal muscles due to irritation of pleural
surfaces) but occasionally they have been found to
cause the common cold.
Myxoviruses
• This group of viruses contains Influenza viruses,
Parainfluenza viruses, and Respiratory Syncytial virus; all
of which can cause the common cold. Influenza viruses
(types A, B, and C) typically cause influenza, which we
will discuss later, however it can also cause the common
cold. In adults the four types of parainfluenza viruses can
cause the common cold, however, in children these viruses
can cause severe disease including croup, bronchitis, and
pneumonia. Respiratory syncytial virus causes the
common cold in adults. In children it is associated with
severe lower respiratory tract infections.
Adenoviruses
• Only a few of the 34 types of adenoviruses
cause the common cold. These infections
are particularly a problem in military
recruits.
Mycoplasma pneumoniae
• This organism is not a virus but rather a
cell-wall deficient bacterium. This organism
can cause respiratory infections that range
from the common cold to
bronchopneumonia.
PATHOGENESIS
• The suspectable person acquires the virus by direct contact or via
inhalation of droplets. The cells lining the nasal passages and the
pharynx are infected by the virus. Rhinovirus attaches itself to the cells
lining the nasal region by binding to ICAM-1 (InterCellular Adhesion
Molecule-1). Inflammatory changes occur with hyperemia, edema, and
leukocyte inflammation. The ciliated columnar epithelial cells are
destroyed and slough off.
• The destruction reaches its peak by day 2 to 5. Regeneration of the
cells begins quite quickly with new cells formed by about the 14th day.
• The acute phase of the illness presents with a runny nose. Large
amounts of material is produced that is clear and mucoid. After 1 to 2
days secondary bacterial infection by the normal flora causes the
secretions to become mucopurulent.
• If severe blockage of the sinus ostia and the eustachian tube occurs it
may lead to paranasal sinusitis or otitis media.
MANIFESTATIONS
• Initially, the patients experiences nasal stuffiness,
sneezing, and headache. Rhinorrhea then occurs
with increasing severity. General malaise,
lacrimation (secretion and discharge of tears), sore
throat, slight fever, and anorexia are common in
moderate to severe cases.
• If the organisms get into the trachea and bronchi
then a tracheobronchitis develops and the patients
may start coughing and feeling substernal
discomfort.
DIAGNOSIS
• This is largely dependent on the patients symptoms, the
localization of the disease process, the time of year, and an
afebrile course. Laboratory culture of the viruses has been
done but is very impractical. Serology is also unnecessary
but is available.
• Prognosis: Usually, the patient totally recovers in 1 week.
Complications are usually related to extension of infection
to the lower respiratory tract resulting in bronchitis, or
inflammation of the nasal ostia/eustachian tube resulting in
paranasal sinusitis/otitis media.
THERAPY and
PREVENTION
• Supportive therapy to ease the patients
discomforts.
• WASH your hands and disinfect
contaminated objects. Avoiding hand
contact with other people during the cold
season.
Pharyngitis
ETIOLOGY and
EPIDEMIOLOGY
• Pharyngitis is common all over the world. In temperate climates it is
most common during the winter and early spring. Acute pharyngitis is
a very common patient complaint in office-based primary care
practices (Family/General practice, pediatrics).
• Many different microbes can cause pharyngitis as a single
manifestation or as part of a more generalized illness (see table below).
• The sore throat, malaise and fever is quite distressing to patients
however, with few exceptions (ex. diphtheria), this illness is benign
and self-limiting.
• Approximately, 90 percent of sore throats in adults and 60 to 75%
of sore throats in children are caused by viral agents.
• The beta hemolytic group A streptococcus (Streptococcus pyogenes)
is the most common bacterial cause of acute pharyngitis accounting
for 15-30% of cases in children and 5-10% of cases in adults.
• The use of an antimicrobial agent is indicated in therapy for "strep
throat" Not treating "strep throat" can result in peritonsillar abscess,
mastoiditis, rheumatic fever.
• Treatment of viral pharyngitis with antimicrobial agents is useless.
Table 1: Pathogen
Occurrence (common,
Associated disorder(s) or
frequent, infrequent,
symptom(s)
uncommon, rare)
Bacterial
Streptococcus group A
Tonsillitis and scarlet
fever
frequent (most common
bacterial cause)
Streptococcus group C
and G (Streptococcus
dysgalactiae; this
species can have either
C or G capsular
polysaccaride.)
Tonsillitis and
scarlatiniform rash
infrequent
Mixed Anaerobes
Vincent's angina
rare
Arcanobacterium
haemolyticum
Scarlatiniform rash;
particularly in teenagers
rare
(Streptococcus
pyogenes)
Chlamydia pneumoniae Pneumonia
Chlamydia psittaci
uncommon
Acute respiratory disease
and pneumonia; bird
rare
fanciers/breeders
Corynebacterium diphtheriae Diphtheria; unvaccinated
populations
rare
Francisella tularensis
Tularemia
(oropharyngeal form)
rare
Mycoplasma
pneumoniae
Pneumonia and
bronchitis
uncommon
Neisseria gonorrhoeea
Tonsillitis; no Rx can
lead to sepsis.
infrequent (sexually
active patients)
Yersinia enterocolitica
Enterocolitis
rare
Yersinia pestis
Plague
rare
Together the viruses are
the most common cause of
pharyngitis.
Viral
Rhinovirus
Common cold
common
Coronavirus
Common cold
common
Adenovirus
Pharyngoconjunctival
common in military recruits
fever and acute respiratory
and boarding schools
disease
Herpes Simplex Virus types 1
Gingivostomatitis
common
Parainfluenza virus
Cold and croup
common in children
Coxsackievirus A
Herpangia (high fever,
vomiting, diarrhea,
common
abdominal pain) and handfoot-and-mouth disease
and 2
Respiratory syncytial virus Bronchiolitis and croup
common in children
Cytomegalovirus
CMV mononucleosis
frequent
Epstein-Barr virus
Infectious mononucleosis
frequent
Influenza A and B viruses Influenza
common in Flu season
Human
Immunodeficiency Virus
(HIV)
Primary HIV infection
infrequent (homosexual
male and heterosexual
female at highest risk)
Rubella virus
German measles
rare; seen in unvaccinated
populations
Measles virus
Measles
rare; seen in unvaccinated
populations
Other unknown viruses
PATHOGENESIS I
• Viral pharyngitis
• The viruses gain access to the mucosal cells lining the
nasopharynx and replicate in these cells. Damage to the
host is often due to damage to cell in which the virus is
replicating.
PATHOGENESIS II
• Bacterial pharyngitis
• Streptococcus pyogenes - person to person spread, The
bacterial cell attaches to the mucosal epithelial cells via F
and M proteins. Cellular and extracellular products appear
to aid the bacterial invasion of the mucosa and its ensuing
clinical manifestations. Direct extension to other sites can
occur but is now quite rare. Nonsuppurative lesions
resulting in rheumatic fever and glomerulonephritis still
occur following strep throat infections.
PATHOGENESIS III
• Corynebacterium diphtheria- The bacterium is not very invasive and
remains localized on the mucosal surfaces of the upper respiratory
tract. Only Corynebacterium diphtheriae lysogenic for the
bacteriophage carrying the toxin gene causes diphtheria. Disease is
spread person to person by droplets in the colder months of the year.
Healthy carriers, convalescent patients, and patients incubating the
disease are the best transmitters of infection to others. Damage to the
pharynx is caused by the diphtheria toxin which kills the mucosal cells
by ADP-ribosylating elongation Factor II. The toxin can also cause
damage to the heart and nerves
• Chlamydia pneumoniae- causes about 5% of the infections. Subacute
onset and pharyngitis are common. Often a biphasic pattern is
observed, with pharyngitis resolving before bronchitis or pneumonia
develops.
Sinusitis
ETIOLOGY and
EPIDEMIOLOGY
• The most common agents responsible for acute sinusitis are:
• Streptococcus pneumoniae, Haemophilus influenzae,
• Chlamydia pneumoniae
• Less common causes of sinusitis are: Staphylococcus aureus
• Streptococcus pyogenes, Gram-negative bacilli, respiratory
viruses
• Chronic sinusitis is usually caused by a combined anaerobic and
aerobic bacterial infection. Infection of the sinuses may follow the
common cold, dental extractions, rhinitis due to allergies, and jumping
into water forcing infected water into the sinuses. Infections of the
sinuses occur mostly in the winter months.
PATHOGENESIS
• Obstruction of the paranasal sinusal ostia impedes drainage of mucus
secretions. Bacteria can grow in these secretions irritating the
underlying mucosa producing more secretions. Death and sloughing
off of the mucosal cells occurs but cells will regenerate after the
infection has cleared.
• Chronic sinusitis can result in irreversible damage to the mucosa and
may cause polyps and mucoceles (mucous polyp, dilatation of a cavity
with an accumulation of mucous) to form.
Respiratory airway infections
Epiglottitis, Laryngitis and
Laryngotracheobronchitis
Overview
• Epiglottitis, laryngitis and laryngotracheo
bronchitis are acute inflammatory diseases
that involve the upper airway. These
diseases are often collectively called croup.
The most common and serious hazard of
these diseases is obstruction of the airway.
This is particularly important for the very
young since their airways are much more
narrow.
ETIOLOGY and
EPIDEMIOLOGY
• The following organisms infect the upper airway:
• Haemophilus influenzae type b (capsular type), causes a
very severe epiglottitis.
• Corynebacterium diphtheriae can also extend to the
larynx from the pharynx.
Laryngitis:
• Parainfluenza viruses there are 4 types of virus. Types 1,3, and 4 are
associated with the common cold and pharyngitis; types 1 and 3 are
associated with croup; and types 1 and 3 are associated with bronchitis
and bronchopneumonia.
• Adenovirus, Echovirus
• Influenza viruses typically cause lower respiratory tract infections but
may infect the upper airway.
• Respiratory Syncytial viruses can cause croup but is usually associated
with bronchiolitis or bronchopneumonia in infants. These infections
are worldwide in distribution.
• Mycoplasma pneumoniae
• Person-to-person contact is the usual means of spread.
• Young children are most susceptible to croup.
• H. influenzae causes infection most commonly in children
ages 6 months to 2 years. By 6 to 10 years of age children
have immunity to the parainfluenza viruses. Parainfluenza
infections can occur anytime in the year.
Acute Bronchitis
ETIOLOGY and
EPIDEMIOLOGY
• The following agents can cause bronchitis:
• Respiratory viruses that infect the upper respiratory tract
• Mycoplasma pneumoniae, Chlamydia pneumoniae,
• The following four organisms cause other symptoms which
are characteristic of infection however bronchitis may be
part of the symptoms observed Bordetella pertussis,
Salmonella typhi, Measles virus, Streptococcus pyogenes ,
• Bronchitis usually occurs after some previous upper
respiratory tract with extension of the infection to the
bronchial tree.
• The predisposing factors for the development of bronchitis
in children include poor nutrition, allergy, deficiencies in
certain IgG subclasses, and rickets. Older predisposed
individuals have emphysema or chronic respiratory
diseases such as tuberculosis.
Bronchiolitis
• This is an acute viral infection with a favorable outcome. The infection
is usually self-limiting and is normally occurs in infants (less than one
year old). The following agents cause bronchiolitis:
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Respiratory Syncytial virus (RSV is the most common)
Influenza viruses
Adenoviruses
Rhinoviruses
Parainfluenza viruses = type 3
Mycoplasma pneumoniae
Influenza
• Although, it is a self-limiting disease severe complications
leading to fatalities are seen in the very young, the elderly,
those with underlying cardiovascular and pulmonary
diseases, and women in their third trimester of pregnancy.
ETIOLOGY and
EPIDEMIOLOGY
• The causative agent of the flu or influenza is the
Influenza virus.
Whooping Cough (Pertussis)
• Bordetella pertussis, is a Gram-negative small bacillus.
The pertussis toxin is believed responsible for most of the
tissue damage. The toxin ADP-ribosylates guanine
nucleotide-binding proteins affecting regulatory
mechanisms in the cells. Other products of importance are
the tracheal cytotoxin, a hemolysin, and a filamentous
hemagglutinin.
• Pertussis occurs worldwide and results in one million
deaths a year.
• Up to 50% of the children getting pertussis can be traced to
adults with chronic cough, a minority of cases are traced to
children passing on the disease, and a significant number
have no obvious source. Most of the severe cases are in
children less than 1 year old.
INTRODUCTION TO LOWER
RESPIRATORY TRACT INFECTIONS
Enumeration of organisms capable of
causing pneumonia
• Bacteria
• Streptococcus pneumoniae, Streptococcus pyogenes (Grp A)
• Streptococcus agalactiae (Grp B), Staphylococcus aureus, Bacillus
anthracis, Other Bacillus sp., Nocardia sp. , Enterobacteriaceae
• Pseudomonas aeruginosa, Acinetobacter sp., Burkholderia
pseudomallei, Burkholderia mallei, Yersinia pestis, Francisella
tularensis, Hemophilus influenzae, Bordetella pertussis
• Neisseria meningitidis, Legionella pneumophila, Legionella-like
bacteria, Bacteroides melaninogenicus, Fusobacterium nucleatum
• Peptostreptococcus sp., Peptococcus sp., Actinomyces sp.
• Mycobacterium tuberculosis, Other Mycobacterium sp. , Mycoplasma
pneumoniae, Branhamella catarrhalis, Chlamydia trachomatis
• Chlamydia psittaci, Chlamydia pneumoniae, Coxiella burnetii (Qfever)
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Viruses
Influenza
Parainfluenza
Cytomegalovirus
Adenovirus
Epstein-Barr Virus
Herpes Simplex Virus
Varicella-Zoster
Coxsackievirus
Measles
Rhinovirus
Respiratory Syncytial Virus
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Fungi
Aspergillus sp.
Mucorales sp
Candida sp.
Histoplasma capsulatum
Blastomyces dermatitidis
Cryptococcus neoformans
Coccidioides immitis
Paracoccidioides brasiliensis
Pneumocystis carinii
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Parasites-Protozoa
Plasmodium falciparum
Entamoeba histolytica
Toxoplasma gondii
Leishmania donovani
Parasites-Nematodes
Ascaris lumbricoides
Toxocara sp.
Ancyclostoma duodenale
Parasites-Cestodes
Echinococcus granulosus