PATH: Pulmonary Infections Flashcards
What is pneumonia?
infection of the lung
What are the two classifications of acute, bacterial pneumonia?
Lobar- involving a whole lobe
Bronchopneumonia
How do almost all bacterial pneumonias start before becoming pneumonia?
MULTIFOCAL BRONCHITIS (may center around bronchi early on)
How common is lobar pneumonia?
very rare
Almost all acute bacterial pneumonias are due to what?
aspiration of saliva containing the pathogen
What is aspiration pneumonia?
pneumonia that is due to (large volume) aspiration of gastroesophageal contents or food misrouted from the oropharynx
What is a pulmonary infiltrate?
a radiologic manifestation of pneumonia or edema or hemorrhage (blood, pus or water).
What is consolidation?
manifestations of alveoli filled with blood, pus or water on physical examination or radiology, again not specific for pneumonia.
How do most types of pneumonia start?
acute inflammation (neutrophilic infiltration)
What occurs during the pathogenesis of pneumonia after acute phase inflammation? When?
subacute phase inflammation with macrophages replacing neutrophils (around day 3 of pneumonia)
What cell type is characteristic of subacute, bacterial pneumonia? What should you NOT get this confused with?
foamy macrophages
DO NOT confuse with “lipid pneumonia” due to lipid aspiration
What is alveolar necrotizing acute bacterial pneumonia commonly due to?
Staph aureus
Pseudomonas aeruginosa
Klebsiella
True or false: acute bacterial pneumonia is typically interstitial.
FALSE: is only interstitial if due to mycoplasma pneumonia
What is acute interstitial pneumonia commonly due to?
viruses
True or false: very few patients with acute bacterial pneumonia are hospatilized for it.
True: only 20%
What is alveolar non-necrotizing acute bacterial pneumonia commonly due to?
Streptococcus pneumoniae (pneumococcus), but can also be due to Legionella species, Mycoplasma species and many other bacterial species.
What is pneumococcal pneumonia?
lung parenchymal infection by Streptococcus pneumoniae (aerotolerant anaerobic Gram-positive diplococcus).
Who is most likely to get pneumococcal pneumonia?
Older men with COPD, who smoke, use alcohol, crack, etc.
What is the pathogenesis of pneumococcal pneumonia?
Normal flora that are acquired by aerosol inhalation that attach to respiratory epithelial cells via platelet activating factor receptor (that can be exposed by influenza neuraminidase), which binds to phosphorylcholine in the pneumococcal cell wall.
What potent cytotoxin is secreted by pneumococci? How does it work?
pneumolysin (binds to cholesterol in membranes and forms lethal pores in erythrocytes and leukocytes)
What is the prototype of pneumococcal pneumonia?
Pneumococcal lobar pneumonia
What are the 4 phases of pneumococcal lobar pneumonia?
(1) day 1: congestion with exudation of serous and frothy, blood-tinged fluid into alveoli
(2) days 2-3: red hepatization with drier, granular, dark red consolidation resembling liver
(3) days 4-7: grey hepatization with continuing consolidation, but color change to grey
(4) day 8 and following: slimy yellowish exudate, resolution without scarring
Describe the microscopic pathology of pneumococcal pneumonia.
acute non-necrotizing alveolitis, which stops at lobar septa because is non-necrotizing
What microscopic pathology lines up to phase 1 of pneumococcal lobar pneumonia?
Phase (1): engorged septal capillaries, with a few erythrocytes, edema fluid and bacteria in alveoli
What microscopic pathology lines up to phase 2 of pneumococcal lobar pneumonia?
Phase (2): continuing congestion, extravasation of red cells and numerous neutrophils and abundant fibrin in alveoli, infection spreading through pores of Kohn into adjacent alveoli
What microscopic pathology lines up to phase 3 of pneumococcal lobar pneumonia?
Phase (3): degenerating dead cells (neutrophils, erythrocytes, sloughed pneumocytes and bacteria) in the alveoli, fibrin nets extending through pores of Kohn, foamy macrophages replace neutrophils
What are the classic symptoms of pneumococcal pneumonia (in young people)?
Sudden single severe shaking chill (rigor), followed by sustained high fever and cough productive of blood-tinged “rusty” sputum +/- pleuritic chest pain.
What are the more common symptoms in heavy drinkers/smokers and older adults?
Increased sputum production and purulence with gradually progressive fever (over 2-3 days).
OR
Confusion, fatigue, and chilly, with no fever or cough.
What are the physical signs of pneumococcal pneumonia?
Low fever (102-103 F) Low tachycardia (HR 90-110/min) Mild tachypnea (RR 20-24/min) Pulmonary crackles Bronchial or tubular breath sounds Dullness to percussion
What do you COMMONLY see on a chest x-ray of pneumococcal pneumonia?
subsegmental alveolar infiltrates without air bronchograms
What value on a blood test gives a poor prognosis for pneumococcal pneumonia?
leukocytosis is a bad prognosis indicator
How do you treat pneumococcal pneumonia?
almost any beta-lactam antibiotic
What is staph aureus pneumonia?
lung parenchymal infection by Staphylococcus aureus
Where is staph aureus pneumonia commonly acquired?
28% of hostital-acquired pneumonias
True or false: lung parenchymal infection by Staphylococcus aureus pneumonia commonly follows viral respiratory infections.
True! (especially influenza)
List the virulence factors of staph aureus.
1) exotoxins (e.g. leukocidins, hemolysins)
2) Protein A
3) Resistance to many commonly used antibiotics in methicillin-resistant strains.
What is the role of Protein A (staph aureus virulence factor)?
binds to TNF receptor 1 and opens path for invasion between epithelial cells
Describe the gross pathology of staph aureus pneumonia.
Heavy plum-colored lungs, which exude bloody fluid on sectioning and develop numerous small abscesses, which enlarge (and in children can be thin-walled “pneumatoceles”).
What pathogenic features commonly accompany staph aureus pneumonia?
Commonly with pleuritis and empyema.
Describe the microscopic pathology of staph aureus pneumonia.
Acute necrotizing bronchitis, bronchiolitis and alveolitis, with abundant neutrophils, fibrin and edema fluid (that can condense into hyaline membranes). Commonly with hemorrhage and abscesses.
What does a chest x-ray of a patient with staph aureus pneumonia look like?
bronchopneumonic (alveolar) infiltrates +/- abscesses, pleural effusions
What is the treatment for staph aureus pneumonia
Oxacillin (or another beta-lactam) for methicillin-sensitive
Vancomycin (or linezolid) for methicillin-resistant.
Which is worse, staph aureus pneumonia or pneumococcal pneumonia? Why?
Staph aureus pneumonia (it is necrotizing and abscessing and has a 50% mortality rate)
What is legionella pneumonia?
Lung parenchyma infection by Legionella species (fastidious Gram-negative bacilli)
What is the habitat of legionella?
Warm water (25-42 degrees) in water heaters, shower heads, air conditioners, etc.
Can hide inside amoebae.
What is the pathogenesis of legionella pneumonia?
Once inhaled or aspirated, attaches to respiratory epithelial cells and macrophages by flagellae and pili. After phagocytosis, evade intracellular destruction by inhibiting phagosome-lysosome fusion
What two legionella genes are involved with inhibiting phagosome-lysosome fusion?
DOT (defective organelle trafficking)
ICM (intracellular multiplication)
True or false: legionella is transmitted from person to person?
FALSE! It is NEVER transmitted from person to person
Describe the gross pathology of legionella pneumonia.
bulging firm rubbery areas of consolidation
Describe the microscopic pathology of legionella pneumonia.
acute non-necrotizing alveolitis, with early infiltration by numerous macrophages (unusual in acute pneumonia)
What specific symptom suggests legionellla pneumonia?
GI symptoms (like diarrhea)
What specific signs suggest Legionella?
neurological signs (like confusion)
What does a chest x-ray of a patient with legionella pneumonia look like?
initially patchy unilobar bronchopneumonic (alveolar) infiltrate that progresses, + (in 50%) pleural effusion
What is the result of a gram stain for legionella?
usually a false negative
What type of culture agar does legionella require?
buffered charcoal yeast extract agar (ideally supplemented with antibiotics and dyes).
How do you treat legionella pneumonia?
newer macrolide antibiotics (especially azithromycin) or respiratory tract quinolones (especially levofloxacin).
True or false: hyponatremia suggests legionella.
TRUE! Hypernatremia (sodium < 130) suggests legionella
What is klebsiella pneumonia?
lung parenchymal infection by Klebsiella species (large rectangular, boxcar, Gram-negative bacilli)
How gets klebsiella pneumonia?
late middle aged males who are debilitated or use alcohol
What are the virulence factors of klebsiella?
Capsule
Beta-lactamase production (and sometimes resistance to multiple antibiotics)
Describe the gross pathology of klebsiella pneumonia.
patchy or lobar consolidation +/- hemorrhagic, necrotizing with abscess formation.
Describe the microscopic pathology of klebsiella pneumonia.
acute neutrophilic alveolitis (+/- hemorrhage, necrosis, abscesses), transitioning to subacute macrophage infiltrate
Describe the sputum of a patient with klebsiella pneumonia.
“currant jelly”
What do you see in a chest X-ray of a patient with klebsiella pneumonia?
Bronchopneumonic or lobar (alveolar) infiltrates, more commonly upper lobes +/- bulging fissure, abscesses, empyema.
What is the treatment of klebsiella pneumonia?
- Combination beta-lactam / beta-lactamase inhibitor
- Fluoroquinolone
- Aminoglycoside
- Trimethoprim-sulfamethoxazole (if not multi-resistant).
What is Pseudomonas aeruginosa pneumonia?
lung parenchymal infection by Pseudomonas aeruginosa (Gram-negative bacilli with pointed ends)
Who commonly gets Pseudomonas aeruginosa pneumonia?
18% of hospital-acquired pneumonias (intubation and neutropenia increase risk)
What is the habitat of Pseudomonas aeruginosa?
water
What is the pathogenesis of Pseudomonas aeruginosa pneumonia?
Once inhaled or aspirated, attach to respiratory epithelial cells; colonization generally precedes infection.
What are virulence factors of Pseudomonas aeruginosa?
- Resistance to many commonly used antibiotics
- Biofilm formation
- Formation of many enzymes (particularly elastase) and exotoxins
Describe the gross pathology of Pseudomonas aeruginosa pneumonia.
firm red areas of hemorrhagic consolidation +/- yellow areas of consolidation with a rim of hemorrhage (target lesions that are not at all specific for Pseudomonas).
WEDGE SHAPED INFARCT (know this is vaso-invasive)
Describe the microscopic pathology of Pseudomonas aeruginosa pneumonia.
Acute necrotizing alveolitis, with groups of long thin, almost filamentous bacilli invading blood vessels from the adventitia (“Pseudomonas vasculitis” with associated hemorrhage and infarction).
What does a chest X-ray of a patient with Pseudomonas aeruginosa pneumonia look like?
Diffusely distributed bilateral bronchopneumonic (alveolar) infiltrates +/- nodular lesions, small abscesses, pleural effusions
What are the characteristics of a culture of Pseudomonas aeruginosa pneumonia?
- Aerobic
- Characteristic sweet grape-like odor
- Green pigment resembling bronze
Why is a diagnosis of Pseudomonas aeruginosa pneumonia difficult?
because positive sputum culture commonly represents only colonization
What is the treatment for Pseudomonas aeruginosa pneumonia?
Combination of an antipseudomonal beta-lactam and antipseudomonal quinolone, etc.
Why is Pseudomonas aeruginosa pneumonia so deadly (87% mortality)?
Pseudomonas pneumonia is much worse than pneumococcal pneumonia mostly because it hits patients already hospitalized with some other bad disease.
Death directly due to pneumonia is as low as 32% of those cases.
What is mycoplasma pneumonia?
lower respiratory tract infection by Mycoplasma pneumoniae
Mycoplasma pneumonia is most common in which seasons?
fall and winter
Who gets pneumonia due to mycoplasma?
usually children and young adults (50% of pneumonia in college students)
Mycoplasma causes what “type” of pneumonia?
atypical (less severe)
What is mycoplasma?
smallest of free-living organisms, fastidious short or filamentous bacilli lacking a cell wall and invisible on Gram stain.
What is the pathogenesis of mycoplasma pneumonia?
Transmitted person-to-person by infected respiratory droplets during close contact, attach to respiratory epithelial cells by adherence proteins and cause illness that is largely immune-mediated, with an incubation period of 2-3 weeks.
What is the gross pathology of mycoplasma pneumonia?
minimal
Describe the microscopic pathology of mycoplasma pneumonia.
lymphoplasmacytic Bronchiolitis with mucosal ulceration and fibrinopurulent exudate in the lumen–> lymphoplasmacytic interstitial pneumonitis extending out from the bronchiolitis, associated with alveolar type 2 pneumocyte hyperplasia.
What are the symptoms of mycoplasma pneumonia?
insiduous onset of malaise, headache, anorexia, low-grade fever –> dry incessant cough
What does a chest x-ray of a patient with mycoplasma pneumonia look like?
patchy areas of airspace consolidation or reticulonodular infiltrate + (in 20%) pleural effusion, unilateral or bilateral, areas of consolidation more common in lower lobes.
What can be found in blood testing of mycoplasma pneumonia patients?
cold agglutinins
What is the treatment of mycoplasma pneumonia?
Azithromycin or levofloxacin
Who gets Tb?
Elderly men from another ethnic background (especially if foreign born)
What is the pathogenesis of Tb?
contagious, spread by the productive cough of heavily infected patients
What are the 4 possible outcomes after inhalation of Tb?
(1) immediate clearance
(2) primary disease
(3) latent disease
(4) reactivation disease.
What is the gross pathology of Tb?
Caseating granulomas (first one in primary infection usually 1 to 1.5 cm, grey-white, with central necrosis resembling cheese, called Ghon focus)
What is a Ghon focus called if it is combined with hilar lymph node involvement?
Ghon complex
What is miliary disease?
Tb pathological presentation characterized by diffusely disseminated small foci of infection resembling millet seeds
What is the microscopic pathology of Tb?
Necrotizing granulomas with epithelioid histiocytes, multinucleated giant cells
What does a chest x-ray of a Tb patient look like?
Patchy or nodular infiltrate in apical- or subapical posterior areas of upper lobes or superior segment of a lower lobe in early chronic tuberculosis (most suggestive of TB if bilateral or cavitary),
OR
small, nodular, sharply defined lesions (granulomas, increased density with caseation) or scarring, atelectasis, mass
OR
Nothing
lesions or large cavities. Pneumonia associated with hilar adenopathy should always suggest what disease?
primary Tb
What is the treatment of Tb?
4 drugs (isoniazid, rifampin, pyrazinamide and ethambutol) for 2 months, followed by 2 drugs (isoniazid and rifampin) for 4 months.
What is histoplasmosis?
Infection by Histoplasma species fungi (which mimic Mycobacterium tuberculosis [“TB wannabe”])
Who gets histoplasmosis?
Very common but mostly asyptomatic–common in Mississippi and Ohio River valleys (near chicken coops and bat caves)
What is the pathogenesis of histoplasmosis?
Inhalation of airborne spores, whose small size allows them to get to alveoli, where macrophages phagocytose them, but do not kill them unless activated by sensitized T lymphocytes in a cytokine pathway involving TNF and INF-gamma.
When does cellular immunity to histoplasmosis develop?
Cellular immunity develops after 10-14 days after exposure. Infection becomes latent in old granulomas in the lungs or lymph nodes.
Describe the gross pathology of histoplasmosis.
tan nodules, masses or areas of consolidation that develop caseous necrosis, may cavitate, and eventually become white, fibrotic and calcified
Describe the microscopic pathology of histoplasmosis.
small 2-5 micron oval basophilic yeast forms with narrow-based budding and often in clusters (sometimes within macrophages) with a variety of tissue reaction (begins with neutrophils)
What does an x-ray of a patient with histoplasmosis look like?
nodules or masses (+/- cavitation) or patchy infiltrates, commonly with hilar or mediastinal lymphadenopathy, but may show reticulonodular infiltrates or miliary disease
How do you treat histoplasmosis?
Itraconazole for mild-moderate disease
Amphotericin for severe disease.
What is aspergillus pneumonia?
Lung parenchymal infection by Aspergillus (that must be distinguished from colonization [ex. non-invasive fungus ball called an aspergilloma] and allergic disease [ex. allergic bronchopulmonary aspergillosis].
Who gets aspergillus pneumonia?
rare, only in immunosuppressive therapy or high-dose corticosteroid therapy
What is the pathogenesis of aspergillus pneumonia?
inhalation of airborne conidia, whose small size allows them to get to alveoli, where they germinate into hyphae and invade, especially blood vessels
Describe the gross pathology of aspergillus pneumonia.
Nodules, commonly with surrounding hemorrhage (may resemble a target, “target lesion”) and associated infarction, or patchy tan-red-brown consolidation, commonly without purulence
Describe the microscopic pathology of aspergillus pneumonia.
necrosis, hemorrhage and (if patient has neutrophils) acute inflammation with regular septate hyphae, 3-6 microns in width, with dichotomous branching (two equal size branches) at acute angles
What is the classic triad of aspergillus pneumonia symptoms?
(in neutropenic patients): fever, pleuritic chest pain and hemoptysis
True or false: aspergillus pneumonia is diagnosed with X-ray.
FALSE: chest X-ray is insensitive (must use CT scan)
What is galactomannan?
major constituent of Aspergillus cell walls released during growth of hypha that can be detected with serum tests (but not good test)
What 3 fungi are very similar looking to aspergillus?
Scedosporium apiospermum Scedosporium prolificans Fusarium
What is the treatment for aspergillus pneumonia/
voriconazole
What is cryptococcal pneumonia?
Lung parenchymal infection by Cryptococcus species fungi. (much less common and much less threatening infection than cryptococcal meningitis)
Do children commonly get cryptococcal pneumonia?
NO- very uncommon in general
What is the pathogenesis of cryptococcal pneumonia?
inhalation of airborne spores (grow well near pigeon feces), whose small size allows them to get to alveoli, where they multiply and resist phagocytosis with their large capsule. Infection becomes latent in old granulomas in the lungs or lymph nodes.
Describe the gross pathology of cryptococcal pneumonia.
soft, tan-grey nodules or masses (“cryptococcomas”) that may have a slimy cut surface and may cavitate, but are not hemorrhagic or calcified
Describe the microscopic pathology of cryptococcal pneumonia.
translucent or faintly basophilic yeast forms (very size-variable) with narrow-based budding surrounded by a large clear space
How is cryptococcal pneumonia diagnosed?
- Biopsy
- Mucicarmine or silver stains
- Cryptococcal antigen test in serum**
How do you treat cryptococcal pneumonia?
fluconazole (or voriconazole).
What is Pneumocystis jirovecii pneumonia?
lung parenchymal infection by Pneumocystis jirovecii (opportunistic)
Who gets Pneumocystis jirovecii pneumonia?
severely immunocompromised people (AIDS)
Describe the gross pathology of Pneumocystis jirovecii pneumonia.
heavy, diffusely consolidated, tan lungs.
Describe the microscopic pathology of Pneumocystis jirovecii pneumonia.
foamy eosinophilic, sparsely cellular, centro-alveolar “honeycomb” exudate +/- lymphoplasmacytic interstitial pneumonia.
What does an x-ray of a patient with Pneumocystis jirovecii pneumonia look like?
diffuse bilateral hazy interstitial infiltrates which become dense alveolar infiltrates
What is elevated in a blood test of a patient with Pneumocystis jirovecii pneumonia?
lactate dehydrogenase
How do you treat Pneumocystis jirovecii pneumonia?
Trimethoprim-sulfamethoxazole
Chronic pneumonia are due to all organisms except?
bacterial (not counting mycobacterial)
What causes interstitial chronic pneumonia?
Pneumocystis jirovecii
Sarcoidosis
Toxoplasmosis
What causes nodular chronic pneumonia?
tuberculosis, histoplasmosis, aspergillosis, cryptococcosis, coccidioidomycosis and blastomycosis
Viral pneumonias typically interfere with what part of the lung?
interstitium
What are the most common causes of viral pneumonia?
Influenza
RSV
CMV causes what type of pneumonia in immunocompromised patients?
interstitial
HSV causes what type of pneumonia in immunocompromised patients?
nodular
What is the most common cause of CAP in the US?
pathogens are detected in <10% of cases, so we cannot really be sure what is the agent for CAP
most commonly identified bug is pneumococcus
