Download Topic: Respiratory and Systemic Disease Structures of the

Topic: Respiratory and Systemic
Disease
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Structures of the Respiratory
System
• Function of the Respiratory System
– Exchange of gases between the atmosphere and the blood
• Respiratory system divided into two main parts
– Upper respiratory system
• Collects air, filters contaminants from the air, and delivers
it to the lower respiratory organs
– Lower respiratory system
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Structures of Upper Respiratory
System, Sinuses, and Ears
– Components of the upper respiratory system
• Nose – external portion of the respiratory system
• Nasal cavity – lined with hairs and a ciliated mucous
membrane to filter and trap particles and microbes
• Pharynx – lined with a ciliated mucous membrane
that pushes contaminants into the digestive system
• Tonsils – aggregations of lymphoid tissue
• Mucus – contains antimicrobial chemicals
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Structures of the Lower
Respiratory System
– Components of the lower respiratory system
• Larynx – contains the vocal cords
• Trachea, bronchi, bronchioles – series of tubes that
allow movement of air through to the lungs
• Alveoli – Air sacs of the lungs where oxygen from air
enters the blood while carbon dioxide diffuses from
the blood into the alveoli to be exhaled
• Diaphragm – muscle involved in breathing
• Protective components include a ciliated mucous
membrane, alveolar macrophages, and secretory
antibodies
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Structures of the Respiratory
System
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Structure of the Respiratory
System
• Normal Microbiota of the Respiratory System
– Lower respiratory system
• Typically microorganisms are not present
– Upper respiratory system
• Normal microbiota limit growth of pathogens
• Normal microbiota may be opportunistic pathogens
• Examples of normal microbiota
– Haemophilus influenzae can colonize the nose
– Staphylococcus aureus is present as normal microbiota in
some individuals without causing disease
– Diphtheroids can colonize the nose and nasal cavity
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Streptococcal Respiratory Diseases
– Signs and symptoms
• Sore throat, difficulty swallowing; may progress to
scarlet or rheumatic fever
– Pathogen and virulence factors
• Caused by Group A streptococci (S. pyogenes)
• Virulence factors include M proteins, hyaluronic
acid
capsule, streptokinases, C5a peptidase, pyrogenic
toxins, streptlysins
– Pathogenesis
• Typically occur when normal microbiota are
depleted, large inoculum is introduced, or adaptive
immunity is impaired
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Streptococcal Respiratory Diseases (cont.)
• Streptococcal Respiratory Diseases
– Epidemiology
• Spread via respiratory droplets
• Occurs most often in winter and spring
– Diagnosis, treatment, and prevention
• Often confused with viral pharyngitis
• Penicillin is an effective treatment
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Streptococcal Respiratory Diseases:
Strep. pyogenes & Strep Throat!
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Diptheria
– Agent - Corynebacterium diptheriae
(G+, non-spore forming bacillus, v-shapes & pallisades)
– Signs and symptoms
• Sore throat, oozing fluid that hardens into a
pseudomembrane that can obstruct airways
– Cirulence factors
• Virulent C. diptheriae produce diphtheria toxin,
prevents polypeptide synthesis and causes cell
death.
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Diptheria pseudo-membrane presentation
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Characteristic Corynebacterium stain appearance
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Diptheria (cont.)
– Pathogenesis and epidemiology
• Spread person to person via respiratory droplets or
skin contact
• Immunocompromised or nonimmune individuals
develop symptomatic infections
– Diagnosis, treatment, and prevention
• Diagnosis based on presence of a
pseudomembrane
• Treated by administration of antitoxin and
antibiotics
• Immunization is an effective prevention
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Sinusitis and Otitis Media
– Signs and symptoms
• Sinusitis: pain and pressure of the affected sinus
accompanied by malaise
• Otitis media: severe pain in the ears
– Pathogen and virulence factors
• Caused by various bacteria such as Streptococcus
pneuomoniae, Staphylococcus aureus,
Haemophilus influenzae, and Moraxella catarrhalis
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Sinusitis and Otitis Media (cont.)
– Pathogenesis and epidemiology
• Bacteria in the pharynx spread to the sinuses via
their connection with the throat
• Sinusitis is more common in adults; otitis media is
more common in children
– Diagnosis, treatment, and prevention
• Symptoms often diagnostic
• No known way to prevent sinusitis
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The “Common Cold”
– >200 varieties
– Endemic
– Signs and symptoms
• Sneezing, runny nose, congestion, sore throat, malaise, and
cough
– Pathogens and virulence factors
• Rhinoviruses are the most common cause, although
numerous viruses cause colds
– Pathogenesis
• Cold viruses replicate in and then kill infected cells
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The “Common Cold” (cont.)
– Epidemiology
• Transmitted via coughing/sneezing, fomites, or
person-to-person contact
– Diagnosis, treatment, and prevention
• Signs and symptoms are usually diagnostic
• Treatment is mainly supportive
• Pleconaril can reduce duration of symptoms
• Hand antisepsis is important preventive measure
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Bacterial Diseases of the Lower Respiratory System
• Lower respiratory organs are usually axenic
• When bacterial infection of the lower respiratory system occurs
life-threatening illness can result
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Bacterial Pneumonias
– Inflammation of the lungs accompanied by
fluid–filled alveoli and bronchioles
– Can be described by the affected region or
the organism causing the disease
• For example, lobar pneumonia involves entire lobe
of the lung
– Bacterial pneumonias are the most serious
and the most frequent in adults
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Pneumoccocal Pneumonia
– Signs and symptoms
• Fever, chills, congestion, cough, chest pain, and short,
rapid breathing
– Pathogen and virulence factors
• Caused by Streptococcus pneumoniae
• Virulence factors include adhesins, capsule, pneumolysin
– Pathogenesis and epidemiology
• Infection occurs by inhalation of bacteria
• Bacterial replication causes damage to the lungs
– Diagnosis, treatment, and prevention
• Penicillin is the drug of choice for treatment
• Vaccination is method of prevention
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Strep pneumoniae - Bacterial pneumonia of the Lower
Respiratory System
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Primary Atypical (Mycoplasmal) Pneumonia
– Signs and symptoms
• Atypical symptoms including fever, malaise, sore throat,
excessive sweating
– Pathogen and virulence factors
• Caused by Mycoplasma pneumoniae
• Virulence factors include an adhesion protein
• No cell wall , stains G- but actually G+!
– Epidemiology
• Nasal secretions among individuals in close contact
spread the bacteria
– Diagnosis, treatment, and prevention
• Treated with tetracycline and erythromycin
• Prevention is difficult because individuals can be infective
despite lack of symptoms
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Mycoplasma pleomorphism in Lower Respiratory System
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Klebsiella Pneumonia
– Signs and symptoms
• Typical pneumonia symptoms combined with a thick,
bloody sputum and recurrent chills
– Pathogen and virulence factors
• Caused by Klebsiella pneumoniae
• G- rod, leading cause of noscomial infections
• Virulence factors include a capsule
– Pathogenesis and epidemiology
• Immunocompromised individuals at greatest risk for
infection
– Diagnosis, treatment, and prevention
• Treated with antimicrobials
• Prevention involves good aseptic technique by health care
workers
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Klebsiella pneumoniae capsule
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Other Bacterial Pneumias
– Cause – Haemophilus influenzae, Staphylococcus aureus,
Yersinia pestis, and Chlamydia species
– Portal of entry – inhalation, also via blood with Y. pestis
– Signs/Symptoms – typical pneumonia symptoms with frothy,
bloody sputum in the case of Y. pestis
– Incubation period – variable depending on cause, although
Y. pestis can produce symptoms in hours
– Susceptibility – typically young children most susceptible
– Treatment – antibiotic treatment
– Prevention – good hygiene; vaccine available for H.
influenzae
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Strep pneumonia is a diplococcus
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Legionnaires’ Disease
– Signs and symptoms
• Typical pneumonia symptoms and possible
complications of the gastrointestinal tract, CNS,
liver, and kidneys
– Pathogen and virulence factors
• Caused by Legionella pneumophila
– Pathogenesis
• L. pneumophila kills human cells, causing tissue
damage and inflammation
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Legionnaires’ Disease (cont.)
– Epidemiology
• The elderly, smokers, and immunocompromised
individuals are at increased risk for infection
– Diagnosis, treatment, and prevention
• Quinolones or macrolides are the drugs of choice
for treatment
• Reduction of bacterial presence in water is
successful control measure
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Legionella pneumophilia colonies
on Charcoal Yeast Extract
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Tuberculosis (M. tuberculosis)
– Pathogenesis
• M. tuberculosis can remain viable for long periods
in aerosol drops (also has non pneumonia form)
• Three types of tuberculosis
– Primary tuberculosis – initial case of tuberculosis disease
– Secondary tuberculosis – reestablished tuberculosis
– Disseminated tuberculosis – tuberculosis involving
multiple systems
– Epidemiology
• Immunocompromised individuals are most at risk
• Tuberculosis is the leading killer of HIV+
individuals
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M. Tuberculosis, acid-fast stain –
shows corded (parallel) growth
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Primary TB Infection Progression
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TB Diagnosis
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Pertussis (Whooping Cough)
– Signs and symptoms
• Initially cold-like, then characteristic cough develops
– Pathogen and virulence factors
• Bordetella pertussis is the causative agent
• Virulence factors include various toxins including
pertussis toxin, adenylate cyclase toxin,
dermonecrotic toxin, and tracheal cytotoxin
– Pathogenesis
• Four phases – incubation, catarrhal, paroxysmal,
and convalescent
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Pertussis (Whooping Cough) (cont.)
– Epidemiology
• Highly contagious; the bacteria spread through the
air in airborne droplets
– Diagnosis, treatment, and prevention
• Symptoms are usually diagnostic
• Treatment is primarily supportive
• Prevention is with the DTaP vaccine
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Bordetella pertussis in cilia of tracheal epithelium
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Inhalational Anthrax
(as opposed to cutaneous)
– Signs and symptoms
• Resemble a cold or flu but progress to severe
coughing, shortness of breath, shock, and death
– Pathogen and virulence factors
• Bacillus anthracis is the causative agent
• Virulence factors include a capsule and secretion
of anthrax toxin
– Pathogenesis and epidemiology
• Anthrax not spread from person to person
• Acquired by endospore contact or inhalation
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Inhalational Anthrax (cont.)
– Diagnosis, treatment, and prevention
• Diagnosis based on identification of bacteria in
sputum
• Early and aggressive treatment with antimicrobials
necessary
• Anthrax vaccine available to military personnel,
researchers, and health care workers dealing with
anthrax patients
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Influenza
– Signs and symptoms
• Sudden fever, pharyngitis, congestion, cough,
myalgia
– Pathogens and virulence factors
• Influenza virus types A and B are the causative
agents
• Hemagglutinin and neuraminidase mutations are
responsible for production of new strains
– Mutations occur via two main processes
» Antigenic drift
» Antigenic shift
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Flu Pandemic 1918-19 – gym-hospital historical photo
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Influenza budding,
also shows H & N sites that make up Hn Nn numbering
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How New Strains of Influenza Virus Occur
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Influenza (cont.)
– Pathogenesis
• Symptoms of influenza are produced by the immune
response to the virus
• Flu patients are susceptible to secondary bacterial infections
due to virally produced damage to the lung epithelium
– Epidemiology
• Hard to calculate mortality – articles place it between 3k and
49k influenza related deaths, depending
• Transmitted via inhalation of airborne viruses or by selfinoculation
• Complications occur most often in the elderly, children, and
those with chronic diseases
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Photo of Budding Virus, ready to shed
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Influenza
(cont.)
Diagnosis, treatment, and prevention
• Signs and symptoms during a community-wide
outbreak are often diagnostic
• Two drugs recommended to treat influenza
– Oseltamivir and zanamivir
• Treatment also involves supportive care to relieve
symptoms
• Immunization with a multivalent vaccine
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SARS –
Severe Acute Respiratory Syndrome
• SARS virus identified in 2003
• Pneumonia leads to respiratory distress and potential
death
• Corona virus family
• Droplet transmission
• 2-10 day incubation
• Symptoms: cough, breathing difficulty, >100.4F,
chills, shaking, headache, aches
• Diagnostics: blood clotting tests, chest exam, Ab
tests, PCR
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SARS – artificial color TEM
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Respiratory Syncytial Virus Infection (RSV)
– Most common childhood respiratory disease
– Signs and symptoms
• Fever, runny nose, and coughing in babies or
immunocompromised individuals
• Mild coldlike symptoms in older children and adults
– Pathogen
• Respiratory syncytial virus (RSV)
– Pathogenesis
• Formation of syncytia can help viruses evade the
immune system and also infect new cells
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Syncytium Formation in RSV Infected Cells
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Respiratory Syncytial Virus Infection (RSV) (cont.)
– Epidemiology
• Transmission occurs via close contact with
infected persons
– Diagnosis, treatment, and prevention
• Diagnosis of RSV infection made by
immunoassay combined with signs of respiratory
distress
• Supportive treatment for young children
• Prevention includes aseptic technique of health
care workers and day care employees
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Hanta Virus –
sin nombre, 4 corners disease
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Hantavirus pulmonary syndrome; Hemorrhagic fever with renal
syndrome
Influenza-like, >50% mortality
Not passed between humans
Carried by rodents, shed in feces and urine
Short incubation – a few days
Early symptoms can rapidly progress to death in a few days
Chills, fever, aches
No prevention or specific remedy, only support
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One of the Hanta Virus carriers…
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Hanta Virus
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Some other Viral Respiratory Diseases
Other viruses that cause respiratory disease in children,
the elderly, or immunocompromised individuals:
• Cytomegalovirus
• Metapneumovirus
– Estimated to be the second most common cause of viral
respiratory disease behind rhinoviruses
• Parainfluenza viruses
– Three strains cause croup and viral pneumonia
– Occur primarily in young children
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Fungal Infections can become
systemic
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Mycoses (fungal infection) of the Lower
Respiratory System Examples
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Some Mycoses of the Lower Respiratory System
• Coccidiodomycosis
– Signs and symptoms
• Resembles pneumonia or tuberculosis
• Infection can become systemic in
immunocompromised persons
– Pathogen and virulence factors
• Caused by Coccidioides immitis
• Pathogen assumes yeast form at human body
temperature
– Pathogenesis
• Enters the body through inhalation of arthroconidia
from the soil
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Coccidiodomycosis (cont.)
– Epidemiology
• Found almost exclusively in southwestern U.S.
and northern Mexico
– Diagnosis, treatment, and prevention
• Diagnosed by presence of spherules in clinical
specimens
• Amphotericin B is the drug of choice for treatment
• Protective masks can prevent exposure to
arthroconidia for those in occupations with high
risk
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Coccidiomycosis lesions in subcutaneous tissue
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Coccidioides immitis in tissue –
characteristic spherules with spores
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Blastomycosis
– Signs and symptoms
• Flulike symptoms
• Systemic infections can produce painless lesions
on the face and upper body or purulent lesions on
various organs
– Pathogen and virulence factors
• Caused by Blastomyces dermatitidis
• Pathogen assumes yeast form at human body
temperature
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Blastomycosis (cont.)
– Pathogenesis and epidemiology
• Enters the body through inhalation of dust carrying
fungal spores
• Incidence increasing among immunocompromised
– Diagnosis, treatment, and prevention
• Diagnosis based on identification of B. dermatitidis
in clinical samples
• Treated with Amphotericin B
• Relapse common in AIDS patients
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Cutaneous Blastomycosis –
disseminated from lung
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Histoplasmosis (Histoplasma capsulatum)
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Most common human systemic fungal infection
Dimorphic ascomycete (yeast at 37F), intracellular
soil associated w/ bats, birds.
Commonly asymptomatic or subclinical, some severe
(~5%)
• cough w/ blood in sputum, skin lesions
• Inhalation leads to attack of alveolar macrophage.
These disperse the infection. Often CMI (cellmediated immunity) rids the infection
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Histoplasmosis progression
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Pneumocystis Pneumonia (PCP)
– Signs and symptoms – difficulty breathing, anemia,
hypoxia, and fever
– Pathogen – Pneuocystis jirovecii (pathogenic
ascomycete)
– Pathogenesis and epidemiology
• Infection through inhalation of droplets containing
the fungus
• Common disease in AIDS patients
– Diagnosis, treatment, and prevention
• Treat with trimethoprim and sulfamethoxazole
• Impossible to prevent infection with P. jiroveci
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Pneumocystis jirovecii Cysts – lung
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