Flashcards in Lower Respiratory Tract infections Deck (86):
What is the key determinant of pneumonia?
Age. Viruses predominate in childhood, and bacteria cause secondary infections
What are the two types of adult pneumonia + their risk factors?
1. Community acquired - risk factors include alcohol abuse, occupational exposure, or underlying condition
2. Nosocomial - immunocompromised or ventilation
What is "atypical pneumonia"?
Pneumonia caused by a pathogen other than Streptococcus pneumoniae
How is the capsule of pneumococcus involved in pathogenesis in the lungs?
Prevents C3b complement deposition and engulfment via alveolar macrophages. Capsule also facilitates evasion of lung surfactant
What is the function of pneumolysin and its role in pathogenesis of pneumonia?
Binds cholesterol, forms a large pore in cell membrane (similar to SLO of GAS or alpha-toxin of S. aureus)
Facilitates evasion of immune response, clearance from nasopharynx. Permits spread from alveoli to bloodstream for bacteremia. Also fixes complement, for immune response.
Other than pneumolysin, what is another major virulence factor that ellicits an inflammatory response?
Cell wall techoic acid and peptidoglycan
Of B. pertussis and S. pneumoniae, which one is only a human pathogen?
THEY BOTH ARE!!
How does pneumococcus relate to AIDS?
Recurrent pneumococcal pneumonia is a presenting manifestation of AIDS (along with Candida esophagitis from earlier)
Why are stroke, alcoholism, drugs, anesthesia, and viral infection all risk factors of pneumococcal pneumonia?
Compromised cough reflex allows pneumococcal entrance into lower respiratory tract
What antibody usually facilitates clearance of pneumococcus from the lower respiratory tract?
What is the primary cause of death in pneumococcal pneumonia?
Rusty lobar (sketchy) pneumonia occurs, with purulent material in alveoli. Inflammation leads to increase in vascular permeability -> fluid accumulation. Disrupted gas exchange due to fluid will suffocate patient
What are two secondary complications of pneumonia?
1. Bacteremia from inflammation
2. Resultant meningitis due to vascular endothelial death and entrance across blood-brain barrier
What is the primary diagnostic tool of pneumonia and what is a common problem?
Sputum is gram-stained -> should be monomicrobial and contain PMNs
Problem: contamination with oropharynx microbes + saliva which can be polymicrobial and have squamous epithelium
What is a common radiological finding of pneumococcal pneumonia?
Bronchopneumia which consolidates to lobar pneumonia "rusty pneumonia"
How does encapsulated vs nonencapsulated Hemophilius influenza pneumonia differ?
Non-encapsulated (non-typable) - more common due to higher carrier rate, lower virulence
Encapsulated (type b) - less common, higher virulence and presents like S. pneumoniae, higher incidence of positive blood cultures vs non-typable
What is a hallmark presentation of Hib in 2-5 year old children?
Pneumonia and cherry red epiglottis (epiglottitis)
What are the predisposing factors of pneumonia via nontypable H. influenzae?
3. Chronic bronchitis
What is the morphology and growth requirements of Hemophilus influenzae?
Small, gram negative coccobacillary rods
Requires factor 5 (nicotinamide) and factor 10 (hematin) for growth
What are the major virulence factors of Legionella pneumophila?
1. Outer membrane proteins for macrophage entry
2. Metalloprotease similar to elastase of P. aeruginosa
3. dot locus
4. Phospholipase C
What is the function of the dot locus in legionella?
dot = defect in organelle trafficking, prevents phagolyososome fusion in macrophages carrying Legionella, and recruits ribosomes to lysosome for nucleotides / amino acids
What is the function of PLC for Legionella?
Damages phospholipid membranes of eukaryotic cells, permitting engulfed bacteria to escape from phagocytic vesicle
How do Legionella species typically survive in the environment?
They are parasites of freshwater and soil protozoa / amoeba (i.e. Acanthamoeba, Naeglaria), and thus live in reservoirs of amoeba/bacteria -> cooling towers of A/c systems, plumbing especially showerheads and faucet aerators, hospital respiratory therapy equipment
How is Legionella spread?
Typically via aerosolization through air conditioning ducts or shower heads and inhaled. Living inside amoeba makes it more resistant to disinfection. Cannot be spread person to person
What are the two diseases caused by Legionella? What are the clinical characteristics?
1. Legionnaire's Disease - severe lobar pnuemonia causing hyponatremia, diarrhea, headaches, confusion, and high fever
2. Pontiac fever - Shorter incubation, self limiting, malaise which is less severe than the pneumonia (less virulent or dead strains)
What are the mechanisms by which Legionella enters the macrophage?
1. Has surface protein for C3 binding and complement-mediated phagocytosis
2. "Coiling phagocytosis" - induces alveolar macrophage uptake in the absence of opsonization via phagocytosis
How is Legionella rapidly diagnosed?
Urine soluble antigen testing, or need a direct lung biopsy since the organism is rarely found in the sputum
How is Legionella typically stained?
Gram stains poorly although it is a gram negative rod, can be visualized via silver staining
What does Acetinobacter cause?
Pneumonia or serious blood/wound infections in immunocompromised
What is significant about Acetinobacter and what is its morphology?
It is multiple-drug resistant and nosocomial, with a high incidence in U.S. Gulf War soldiers
Morphology: gram negative coccobacillus (similar to H. influenzae or B. pertussis)
What are the three major virulence factors of Mycoplasma pneumoniae?
1. Adhesin - which binds sialic acid-containing glycolipids / proteins on bronchial epithelium
2. Hydrogen peroxide and superoxide radicals to cause tissue damage
3. Autoantibodies react with many body tissues due to homology between host cells and mycoplasma glycolipids
What type of pneumonia is characteristic of Mycoplasma and who gets it?
Highly infectious pneumonia often had by young people (<30 years) living in close quarters (i.e. military), called "walking pneumonia"
X-ray appears way worse than it actually is, with diffuse infiltrates
How is Mycoplasma cultured and detected?
Cultured on Eaton's agar, lacks a cell wall and has a very small genome (Gram indeterminate). Sputum will not show organisms and organism grows very slowly.
Often detected via serodiagnosis for IgM antibodies
What are the two forms of Chlamydia pneumonia?
1. Elementary body (EB) - enters the columnar epithelial cells of bronchioles
2. Reticulate body (RB) - replicate and rely on host ATP before reorganizing into elementary bodies
What is the clinical presentation of Chlamydia pneumonia?
Atypical or walking pneumonia, similar clinical picture to Mycoplasma pneumoniae, presents in schoolchildren or young adults.
Can also cause pharyngitis and bronchitis
What is the morphology of Chlamydia pneumonia and how can it be told from Chlamydia trachomatis?
Gram negative outer membrane but no cell wall, coccobacillus
Can be told apart via RNA / PCR, or importantly does NOT form "glycogen-containing inclusion bodies" like C. trachomatis
In what scenario does S. aureus cause pneumonia?
Secondary to some other lung insult such as influenza, with pathology similar to other bacterial pneumonias
What is empyema?
Purulent infection of pleural space via Staph aureus. Can also cause lung abscess.
What are the two main virulence factors of M. tuberculosis and how do they work?
1. Mycolic acid (cord factor) - consists of long chain fatty acids >60C, provides resistance to disinfection and drying. Cord factor is a mycolic acid complex which promotes hypersensitivity granuloma via TNFalpha and tissue damage
2. Lipoarabinomannan - glycolipid which suppresses T cell prolferation and prevents macrophage activation
What are the symptoms of Mycobacterium avium complex and who does it infect?
TB-like disease causing fever and wasting, as well as diarrhea
Infects immunocompromised, especially AIDS patients with CD4 < 50 cells / mL
What is Hansen's disease?
Leprosy - degenerative disease of skin and nerves caused by Mycobacterium leprae
Who most often gets TB?
AIDS patients (immunocompromised reactivation of primary infection) and immigrants (From developing world)
Outbreaks are in closed communities
Where does reactivation TB most often grow and why?
In the apex of the lung, which has the highest oxygen tension (greatest relative ventilation / perfusion ratio, most available oxygen for M. tuberculosis to use)
What are the symptoms of primary TB in most people and what can it progress to?
In 95% of people, infection is quickly resolved with a localized lung lesion.
In 5%, can cause disseminated infection with nodules forming around the body like millet seed, called "miliary TB"
What is a Gohn complex?
The lung granuloma + enlarged hilar lymph nodes characteristic of primary TB infection
What are the most common sites of miliary / disseminated TB and how does this happen?
Granulomas are broken up / necrotic tubercles erode, and TB disseminates into small granulomas around the body.
Common sites: Liver, spleen, bone, and meninges
What are the common causes of reactivation TB?
Age, immunocompromised, alcoholism, diabetes
Why does TB primarily grow in the lung?
It is an obligate aerobe
How does TB grow in the lung?
Engulfed by alveolar macrophages and carried to lymph nodes, disallows phagolysosome fusion and grows intracellularly
What is the cell-mediated response to TB?
Helper and cytotoxic T cells activate alveolar macrophages, which prevent replication of TB and wall off the bacteria, forming a granuloma. It has a caseous (cheesy) and necrotic consistency
What causes the characteristic fever and weight loss of TB?
Cytokine response to organism (TNF). Loss of this will cause reactivation / disseminated TB
Why is loss of DTH reaction to PPD a bad sign? How does the tuberculin test work?
It is a bad prognostic indicator because it means there is no immune response to the organism.
PPD / Tuberculin skin test is autolyzed bacteria containing antigens which are injected into skin and should cause DTH reaction. (Mantoux test)
When does DTH first become positive?
About 6 weeks after primary infection, when the first hypersensitivity granulomas are being formed
What stain is used for TB?
Ziehl-Neelsen - acid-fast stain which collects in the Mycobacterial mycolic acids
When are IFNy-release assays used?
When patients are vaccinated with BCG or HIV Mantoux-test negative, uses a different TB antigen than BCG, measure T cell IFNy release in response to antigens.
What is P. aeruginosa's primary two virulence factors for survival in the lung?
1. Alginate capsule - mucoid phenotype in lungs
2. Elastase - degradation of lung elastin
How is P. aeruginosa MDR?
Mutations leads to loss of porin and decreased entry of antimicrobials, and LPS can be altered so it doesn't bind Antibiotics
What bacteria, other than S. aureus, can cause acute pneumonia, empyema, and abscess?
Who is most prone to P. aeruginosa pneumonia and what particular age group?
CF patients, because excess mucus provides physical barrier to drugs. Early in the disease they are haunted by S. aureus, later it's multiple-drug resistant P. aeruginosa
What are the defining characteristics of P. aeruginosa?
Gram negative rod
Identified by oxidative metabolism in OF dextrose tubes
What causes Farmer's lung?
Inhalation of large numbers of infectious conidia of Aspergillus, leading to acute pneumonia / lung abscess by the environmental mold
What factors predispose someone to Aspergillus infection? What is the primary host defense?
Asthma, chronic bronchitis, TB (due to causing cavitation for aspergillosis), and immunosuppression
Primary host defense is neutrophils which act on invasive hyphae
How is Aspergillus identified clinically?
Lung aspiration, bronchial lavage, or biopsy
-> will be easily identified, grows well
How does Histoplasma capsulatum grow?
It is dimorphic, but its yeast form grows within human macrophages and survives oxidative bursts
Where is Histoplasma found?
Grows in soil, especially with abundance of bird and bat droppings, in Ohio / Mississippi River Valleys
What type of disease does Histoplasma cause and how common is this?
Causes TB-like disease, with primary lesions resembling pulmonary TB. Exposure is common but disease is rare. Activated macrophages via T cells will inhibit intracellular growth
How is Histoplasma clinically identified?
Grows slowly over weeks on blood and Sabouraud agar. Typically has TB-like X-ray findings on exam. Sputum sample will not be useful - biopsy required
What test is used to determine past Histo exposure?
Serological tests for DTH reaction with mycelial antigen - cross-reactive with other pathogens.
This can also be done by urine antigen testing.
What is the major pathogenic difference of Blastomyces dermatitidis from H. capsulatum?
B. dermatitidis yeast cells are extracellular, not in macrophages
What are the 3 B's of Blastomyces?
Blastomyces - Broad Based Budding
They form large, thick-walled yeast cells with large buds
What is the geographic distrubution of Blastomyces vs Histo?
Same area - middle / southeastern US
What is the lung presentation of Blasto?
Chronic pneumonia may mimic pulmonary tumor or TB
Where does Blasto typically disseminate to?
The skin very commonly (dermatiditis), but also the bone (osteomyelitis)
Leads to necrosis and fibrosis at infected area -> disfigurement
What is the only good way to identify Blasto?
Via biopsy for yeast with broad buds -> there is no skin test and antigenic cross-reactivity is too high
What are the growth phases of Coccidioides immitis? How do these evade immune response
Spherules are invasive tissue form which prevent phagolysosome fusion by neutrophils / macrophages. They reproduce via endospores.
Spores cause a large inflammatory response and cause formation of granulomas.
What and where in the US is the infection caused by Coccidioides? What are the stages?
Valley fever - Southwestern US
cough, chest pain, and myalgia which can become chronic pneumonia in T-cell compromised and disseminate to skin and bones
Are Histo and Coccidioides infections always obvious?
No, most cases are subclinical
What T / B cell combinations indicate a poor vs good response to Coccidioides?
Immunity is primarily T-cell mediated
Good: Strong T cell response with little antibody
Bad: Increased non-protective B cell response (complement fixation does not work)
What are the primary diagnostic methods of Coccidioides?
1. Spherules on histological biopsy
2. Coccidioidan DTH test - positive 1-4 weeks after onset
How is Coccidioides spread?
Via dust carrying arthroconidia. Incidence has been increasing due to global warming
What are the relative sizes of Histo, Blasto, and Coccidio?
Coccidio > Blasto > Histo
Blasto is ~ same size as RBC
Is Pneumocystis jiroveci a common infection, and how can it be spread?
Yes, common infection with low virulence. 75% of people have antibodies by age 4.
Aerosol transmission, often from healthcare workers to immunocompromised like cancer wards and premature infants
What is the most common opportunistic infection in AIDS?
Pneumocytosis - loss of T cell function when count falls below 200 cells / mL
What is done to get a PCP sample?
Bronchoalveolar lavage for a sputum sample via hypertonic saline, especially in AIDS patients since they normally won't produce sputum.
Can also biopsy
How is PCP diagnosed once a sample is taken?
Histologically - extracellular cysts + trophozoites seen by fluorescence microscopy or Giemsa stain.
Can also immunofluoresce via monoclonal antibody, or PCR
What are the clinical symptoms of pneumocystosis? How do patients die?
Mild or low grade fever
Typical signs of pneumonia absent - NONPRODUCTIVE COUGH
Progressive dyspnea and tachypnea with cyanosis due to hypoxia.
Patients die by asphyxiation