Comprehensive Notes on Respiratory System Diseases

Diseases of the Respiratory System

Learning Objective

• Explain the ranking of the respiratory tract as the most commonly infected system.

Respiratory System

• A major portal of entry for infectious organisms.
• Divided into two tracts based on structure and function.
• Each part has different types of infections.

Innate Defenses of the Respiratory System

• Mucociliary escalator:
  • Traps debris and bacteria.
  • Moves them to the esophagus for removal.
• Alveolar macrophages:
  • Important part of the host defense in the alveoli.
  • Phagocytose pathogens and debris in the lower respiratory tract.
• Muscles of the chest wall and diaphragm:
  • Essential for coughing.
  • Clear secretions from the respiratory system.

Bacterial Infections of the Upper Respiratory Tract

• Otitis media
• Pharyngitis (strep throat)
• Scarlet fever
• Diphtheria

Otitis Media

• Can be viral or bacterial.
• Most common between ages 3 months to 3 years.
• Etiologic agents:
  • Streptococcus pneumoniae
  • Staphylococcus aureus
  • Haemophilus influenzae

Otitis Media Complications

• May spread locally, resulting in:
  • Acute mastoiditis
  • Petrositis (infection of temporal bone)
  • Labyrinthitis
• Intracranial spread (extremely rare):
  • Meningitis
  • Brain abscess
  • Subdural empyema
  • Epidural abscess
  • Lateral sinus thrombosis
  • Otitic hydrocephalus

Mastoiditis

• Uncommon, occurs when untreated otitis media spreads.
• An abscess may form in the bone.
• Symptoms:
  • Red, swollen, and tender skin covering the mastoid process.
  • Fever
  • Pain around and within the ear
  • Creamy, profuse discharge from the ear
  • Persistent and throbbing pain
  • Progressively worsening hearing loss

Sinusitis

• Very common.
• Usually a bacterial super-infection after sinus drainage is compromised.
• Signs and symptoms:
  • Pain
  • Tenderness
  • Congestion and obstruction in the nose
  • Reduced ability to smell (hyposmia)
  • Bad breath (halitosis)
  • Productive cough (especially at night)
  • Swelling over the affected sinus

Pharyngitis

• Classic infection: strep throat.
• Etiologic agent: Streptococcus pyogenes
  • Can cause abscesses on the tonsils.
  • Can cause complications of scarlet fever, toxic shock syndrome, and rheumatic fever.

Scarlet Fever

• Caused by Group A Streptococci (Streptococcus pyogenes).
• Seen in children under the age of 18.

Scarlet Fever Pathogenesis

• Symptoms begin with the appearance of a rash:
  • Tiny bumps on chest and abdomen.
  • Appears redder in armpits and groin.
  • Lasts 2-5 days.
• Very sore throat with white or yellow papules.
• Fever of 38.3°C (100.9°F).
• Lymphadenopathy.
• Headache, body aches, and nausea.
• Tongue coated with bacteria.

Diphtheria

• Etiologic agent: Corynebacterium diphtheriae

Diphtheria

• Localized infection: severe pharyngitis.
• May be accompanied by pseudomembrane in the throat composed of fibrin, leukocytes, cell debris, and dead bacteria.

Pathogenesis of Diphtheria

• Transmitted via:
  • Droplet aerosol
  • Direct contact with colonized skin
  • Fomites
• Produces a toxin:
  • Myocarditis
  • May involve multiple organ systems
  • May also involve the skin: Simple pustules to non-healing ulcerations
• Prevention: Vaccination with the DTaP vaccine

Viral Infections of the Upper Respiratory System

• Rhinovirus
  • Common head cold
• Parainfluenza
  • Types 1 and 3

Rhinovirus

• Several hundred serotypes.
  • Fewer than half have been characterized.
  • 50% are picoronaviruses (smallest and simplest).
  • Single-stranded RNA.
• Major cause of mild upper respiratory tract infections.

Pathogenesis of Rhinoviruses

• Infection is seen throughout the year.
  • Epidemic in spring and early fall.
• Incubation period: 2-3 days.
• Acute symptoms: 3-7 days.
• Infection is mild with little damage done to the body.

Parainfluenza Virus (HPIV)

• 4 types of parainfluenza virus; Types 1 & 3 most important.
• Belong to paramyxovirus group
  • Single stranded RNA virus
  • Contains hemagluttinin and neuraminidase
• Serious problem in infants and small children

Parainfluenza vs. Influenza

Pathogenesis of Parainfluenza

• UPPER RESPIRATORY:
  • Fever
  • Runny nose (rhinorrhea)
  • Cough
  • Sore throat
  • Sneezing
  • Wheezing
  • Ear pain
  • Decreased appetite
• LOWER RESPIRATORY:
  • Croup (an infection of the larynx, trachea, and bronchi)
  • Bronchitis
  • Bronchiolitis
  • Pneumonia

Comparison of HPIV1 and HPIV3

Bacterial Infections of the Lower Respiratory Tract

• Bacterial pneumonia
• Mycoplasmal pneumonia
• Tuberculosis
• Pertussis
• Inhalation anthrax
• Legionnaire’s Disease
• Q Fever
• Psittacosis

Bacterial Pneumonia

• One of the most serious infections
• May be caused by a variety of organisms

Community Acquired Pneumonia

• High risk groups:
  • Elderly
  • Children under 2 years
  • African-Americans
  • Native Americans
  • Alaska Natives

Pneumococcal Pneumonia: Streptococcus pneumoniae

• Signs and symptoms
  • Fever over 39°C (102.2°F)
  • Chest pain
  • Purulent sputum

Mycoplasmal Pneumonia

• Etiologic agent:
  • Mycoplasma pneumoniae

Mycoplasmal Pneumonia

• Mild form of pneumonia
• Accounts for 10% of all pneumonias
• “Walking Pneumonia”
• Most common age: between 5 and 15
• Found in temperate climates

Pathogenesis of Mycoplasmal Pneumonia

• Incubation period: 2–15 days
• Insidious onset:
  • Fever
  • Headache
  • Malaise
• Infection affects the trachea, bronchi, and bronchioles
  • May extend into the alveoli
• Organisms shed in upper respiratory secretions
  • 2-8 days before symptoms
  • 14 weeks post-infection

Pathogenesis of Mycoplasmal Pneumonia

• Infection causes:
  • Mild tracheobronchitis
  • Sore throat
  • Otitis media
• Chief complaint: Persistent, nagging, unproductive coughing

Pulmonary Tuberculosis

• Estimated 2 billion people infected globally
• HIV/AIDS having a significant impact
• Poverty and poor living conditions
• Drug resistance due to non-compliance

Tuberculosis

• Signs and Symptoms
  • Initial symptoms similar to other respiratory tract infections
    • EXCEPT
  • Fever (38° C; 100.4°F)
  • Fatigue
  • Weight loss
  • Chest pain
  • Shortness of breath
  • Hacking cough
  • Hemoptysis

Tuberculosis Trends

• One quarter of the world’s population are carriers
• 50,000,000 people are infected with multiple drug resistant (MDR) strains of TB
• 80% of US cases are foreign-born
• TB is a re-emerging disease

Tuberculosis

• Etiologic agent:
  • Mycobacterium tuberculosis
  • Acid-fast+ bacillus/ Weakly Gram+ bacillus

Pathogenesis of Tuberculosis

• Primary: occurs when host encounters pathogen for the first time
  • Organisms move to alveoli
  • Cell mediated immune response begins
  • If primary lesion is not contained → tubercles/granulomas

Pathogenesis of Tuberculosis

• Tubercles: aggregates of macrophages containing bacteria
  • Surrounded by fibroblasts and lymphocytes
  • Center of tubercle: caseous necrosis
  • Calcified: Ghon complex

Pathogenesis of Tuberculosis

• Secondary: also called latent
  • Due to reactivation of old lesions
    • Advanced age
    • Immunocompromization due to co-infection with HIV/AIDS
  • OR Gradual progression from primary TB

Diagnosis of Tuberculosis

• Diagnosis dependent upon
  • PPD: purified protein derivative skin tests
    • Mantoux or Tine
  • Chest film showing tubercles or consolidation
  • Sputum sample with acid-fast staining
  • Biopsy

Treatment of Tuberculosis

• Triple therapy cocktail
  • Isoniazid (INH)
  • Rifampicin (RFP)
  • Pyrazinamide (PZA)
  • All three taken once a day for two months
  • INH and RFP are taken for nine more months
• Compliance with drug therapy and follow-up testing is very important
• Compliance may be difficult because of side effects of drug therapy
  • Toxicity
  • Liver
  • Kidney

Directly Observed Therapy

• Delivery of scheduled drug doses by a health care worker
  • Patient’s ingestion or injection of drugs is directly administered, observed, and documented
• DOT helps prevent
  • Spread of TB
  • Occurrence of MDR-TB

Whooping Cough

• Highly contagious
• Infects 80-100% of susceptible individuals
• Mortality is highest in infants and children under 1 year of age
• Whooping cough is a re-emerging disease

Whooping Cough

• Etiologic agent: Bordetella pertussis
• Pertussis is the medical terminology for whooping cough
• Prevention: DTaP vaccine

Pathogenesis of Pertussis

• Has an affinity for ciliated bronchial epithelium
• After attaching it produces a tracheal toxin
  • Immobilizes and destroys the ciliated cells
  • Persistent cough arises from inability to move mucus
• Pertussis does not invade the cells or tissues of the respiratory tract
• Incubation period: 7-10 days

Stages of Pertussis

• Primary stage: catarrhal
  • 1-2 weeks
  • Persistent perfuse and mucoid rhinorrhea
  • Sneezing, malaise, and anorexia
  • Highly communicable at this stage

Stages of Pertussis

• Secondary stage: paroxysmal
  • 2-4 weeks
  • Persistent coughing
  • 50 times a day
  • Characteristic whooping sound
  • Apnea may follow esp. in infants
  • Significant increase in lymphocytes

Stages of Pertussis

• Tertiary stage: convalescence
  • Frequency and severity of coughing and other symptoms gradually decrease
  • Lasts from 6 to 10 weeks

Complications of Pertussis

• Super or secondary infection with Streptococcus pneumoniae
• Convulsions
• Subconjunctival and cerebral bleeding
• Hypoxia and anoxia

Inhalation Anthrax

• Anthrax naturally is a disease of herbivores
• Recent interest because of its use as a bioweapon

Inhalation Anthrax

• Produces a severe and sudden-onset pneumonia:
  • 90% mortality
  • Respiratory failure
  • Cardiac failure

Pathogenesis of Anthrax

• Etiologic agent: Bacillus anthracis
  • Spore-forming
  • Produces a capsule that aids in colonization of lung tissue

Pathogenesis of Anthrax

• Powerful exotoxin
• Symptoms:
  • 1-5 days non-specific malaise
  • Mild fever
  • Non-productive cough
  • Progressive respiratory distress
  • Cyanosis
• Rapid and massive spread to the CNS and bloodstream followed by death

Legionnaires’ Disease

• Unrecognized as a disease prior to 1976
• Organism is ubiquitous in fresh water
  • Lives inside Acanthamoeba
• Healthy people: undetected
• Infection is seen in less than 5% of the population

Pathogenesis of Legionnaires' Disease

• Etiologic agent: Legionella pneumophila
• Transmitted as a humidified aerosol
• Facultative intracellular parasite

Pathogenesis of Legionella pneumophila

• Infect alveolar macrophages
• Infected macrophages show coiled morphology

Pathogenesis of Legionella pneumophila

• Causes severe toxic pneumonia
  • Myalgia
  • Headache
  • Rapidly rising fever
  • Chills
  • Pleuritic chest pain
  • Vomiting
  • Diarrhea
  • Liver dysfunction
• Serious cases show disease progression 3-6 days
  • Shock
  • Respiratory failure
• Mortality rate: 15% in the community; 50% in hospital settings
  • High population of immunocompromised and immunosuppressed

Q Fever

• Grows well in the placenta of animals
  • Contaminated soil
• Transmission: ingestion of unpasteurized milk and dairy products
• Zoonotic infection
  • Cattle
  • Sheep
  • Goats

Q Fever Pathogenesis

• Etiologic agent: Coxiella burnetii
  • Incubation: 9-20 days
  • Chills
  • Fever
  • Headache
  • Mild hacking cough
  • Abnormal liver function

Psittacosis (Ornithosis)

• Zoonotic pneumonia
• Contracted by inhalation of bird droppings
• Parrots and their relatives are the most common hosts

Pathogenesis of Psittacosis

• Etiologic agent: Chlamydia psittaci
• Common name: Parrot Fever
• Acute infection
  • Fever
  • Headache
  • Muscle aches
  • Dry hacking cough
  • Bilateral pneumonia
• Occasional systemic complications
  • Myocarditis, endocarditis, hepatitis

Viral Infections of the Lower Respiratory Tract

• 75-80% of all acute respiratory tract infections in the US are of viral origin
  • Everyone gets 3-4 per year
• Incidence varies inversely with age
  • Greatest in young children

Common Characteristics of Viral Lower Respiratory Tract Infections

• Short incubation period
  • 1 to 4 days
• Transmission from person to person
  • Can be direct or indirect transmission
    • Direct-through droplets
    • Indirect-through transfer of contaminated secretions

Influenza

• Orthomyxovirus
• Single stranded RNA
• 3 serotypes of influenza virus
  • Serotype A: Infects all mammals and birds. Responsible for all flu pandemics
  • Serotype B: Infects humans and seals
  • Serotype C: Infects humans and pigs

Influenza

• Significant health concern due to high mutability
• Aquatic birds are the RESERVOIR; humans are the HOSTS
• Outbreaks described since early 16th century
• Occur more frequently in winter
• Direct droplet transmission most common form of spread

Influenza Outbreaks

• Pandemics throughout history are shown in a figure, with specific subtypes such as H1N1, H2N2, and H3N2 causing significant outbreaks.

Pathogenesis of Influenza

• Acute influenzal syndrome:
  • Short incubation time: 2 days
  • Symptoms:
    • Fever
    • Myalgia
    • Headache
    • Shaking chills
    • Maximum severity in 6-12 hours
    • Non-productive cough
  • Acute symptoms can last 3-5 days

Pathogenesis of Influenza

• Respiratory epithelium may not be restored for 2-10 weeks
• Progressive infection may develop
  • Affects the tracheobronchial tree and lungs
  • Bacterial superinfection
• Mortality rate for uncomplicated influenza: 0.1-2.5%
• Mortality rate for influenza with a bacterial super-infection: 75-80%
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Staphylococcus aureus

Respiratory Syncytial Virus (RSV)

• Community outbreaks occur in the late fall to early spring
  • Outbreaks last 8-12 weeks
  • Can involve 50% of families with small children
  • Older sibling brings infection home
  • Young children to infants are most commonly infected

Pathogenesis of RSV

• Virus shed:
  • Children: 5-7 days
  • Infants: Up to 20 days
• Affects the bronchi, bronchioles, and alveoli
  • Plugging of smaller airways with mucus, necrotic cells, and fibrin
• Incubation period: 2-4 days
  • Onset of rhinitis
  • Severity of these symptoms peaks in 3 days

Pathogenesis of RSV

Clinical signs:

• Acute signs: last 10-14 days
  • Hyperexpansion
  • Hypoxia
  • Hypercapnia
  • Pulmonary collapse
• Infection is mild in older children and adults
• Can be fatal in infants
  • Hospitalized infants mortality rate 1%
  • Immunocompromised: 15%

Hantavirus Pulmonary Syndrome

• In the US most common form is “Sin Nombre”
• Infections associated with fluctuations in rodent populations

Sin Nombre

• Transmission: dried rodent excreta
  • Inhalation
  • Conjunctiva
  • Breaks in skin
• High mortality rate
  • 50-70%
  • Native American population
  • ARDS (Adult Respiratory Distress Syndrome)

Fungal Infections of the Lower Respiratory Tract

• Fungal spores are ubiquitous
  • Found in soil
  • Found in homes
  • Resident flora

Pneumocystis Pneumonia

• Etiologic agent: Pneumocytis (carinii) jiroveci
• Common in AIDS patients
  • Onset is insidious: can be present for 3-4 weeks
  • Early years of AIDS epidemic diagnostic for HIV
• Ground glass appearance on film

Pathogenesis of Pneumocystis Pneumonia

• Symptoms:
  • Progressive dyspnea
  • Tracheal pneumonia
  • Cyanosis
  • Hypoxia
  • Non-productive cough in 50% of patients

Pathogenesis of Pneumocystis Pneumonia

• Fungal infiltrates spread from hila throughout entire lung
• Decreased O2 capability
  • Decreased saturation of arterial blood
  • Decreased lung vital capacity
• Death occurs through progressive asphyxiation
• Lesions may occur in other areas of the body

Blastomycosis

• Etiologic agent: Blastomyces dermatitidis
• Men ages 20-40 most commonly affected: hunters

Pathogenesis of Blastomycosis

• Infection of the lungs is gradual
  • Fever, chills, and drenching sweats
  • Chest pain, difficulty breathing, and cough may develop
• When infection spreads it targets
  • Skin
  • Bones
  • Genitourinary tract
• May spontaneously heal

Histoplasmosis

• Etiologic agent: Histoplasma capsulatum
• Occurs in soil contaminated with bat or bird feces
• Commonly found in all areas except tundra and taiga
• Most cases are asymptomatic

Pathogenesis of Histoplasmosis

• Some cases present with mild fever and cough
• Majority of cases never go past granuloma formation
  • Last a few days to several weeks
  • Most cases resolve spontaneously
• Severe cases:
  • Chills
  • Malaise
  • Chest pain
  • Extensive pulmonary infiltrate

Coccidioidomycosis

• Etiologic agent: Coccidioides immitis
• Causes "Valley Fever"
• Restricted to certain geographical regions

Pathogenesis of Valley Fever

• 50% of infected individuals are asymptomatic
• Symptoms: signs may occur 1-6 weeks post-exposure
  • Malaise
  • Cough
  • Chest pain
  • Fever
  • Arthralgia
• Most cases resolve spontaneously
• Immunocompromised: may see disseminated form or coccidiodal meningitis

Aspergillosis

• Etiologic agent: Aspergillus spp.
• Wide geographic distribution
• Infections seen with improperly maintained air-conditioning systems

Aspergillosis

• Invasive form rapid progression to death
• Seen in immunocompromised or those with COPD, asthma, and TB

Pathogenesis of Aspergillosis

• Colonization leads to tissue invasion
  • Hemoptysis
  • Acute pneumonia
• Pneumonia: multifocal pulmonary infiltrates and high fever
  • Prognosis: grave
  • Invasive aspergillosis: 100% mortality