Flashcards in Thirty Three Deck (34):
What does suboptimal humoral immunity lead to? Suboptimal cell mediated immunity? What are some other risk factors for pulmonary infection?
In general, suboptimal
humoral immunity and/or suboptimal nonimmune defense
systems increase the risk for pyogenic bacterial infection,
whereas suboptimal cell-mediated immunity increases the
risk of infection by intracellular and low-virulence organisms,
typically viruses and some bacteria. Other risk factors for the
development of respiratory tract infection include decreased/
absent cough refl ex, reduced phagocytic/bactericidal activity
of alveolar macrophages (eg, by alcohol, smoking, anoxia,
oxygen intoxication), pulmonary congestion/edema, accumulation
of airway secretions (eg, cystic fi brosis or distal to an
obstruction), and mucociliary dysfunction, both congenital
(eg, immotile cilia syndrome, Kartagener syndrome) and
acquired (eg, viral illness, toxic effects of inhaled smoke).
What are 3 morphological patterns found in respiratory tract infection?
This chapter will focus on the pathology of infectious
disease and is organized by general morphologic similarities.
There are three major morphologic patterns in infections of
the respiratory tract: intra-alveolar accumulation of neutrophils,
with or without abscess formation; interstitial expansion
by mononuclear infl ammatory cells; and granulomatous
infl ammation. Lung infections can also be organized based on
their clinical settings rather than by their morphologic patterns
What occurs in suppurative bacterial pneumonia? Why? How is it subclassified?
In suppurative bacterial pneumonia, there is consolidation
(ie, solidifi cation) of lung parenchyma due to the accumulation
of neutrophil-rich intra-alveolar exudate (Fig. 34.1). The
consolidation of bacterial pneumonia is classically subclassifi
ed into two patterns: lobar pneumonia and bronchopneumonia
(or lobular pneumonia).
What occurs in lobar pneumonia? How can it be identified? Describe the 3 phases?
In lobar pneumonia, there is consolidation of contiguous
airspaces, typically an entire lobe (Fig. 34.2). Lobar pneumonia
is identifi able on an x-ray by a well-circumscribed
radiopacity correlating to the affected lobe. Lobar pneumonia
evolves through phases of congestion, red hepatization,
gray hepatization, and resolution (Fig. 34.3).
During the congestion phase, the affected lobe is heavy,
red, and boggy; histologically, there is vascular congestion, accumulation of intra-alveolar neutrophils, and pulmonary
edema. Eventually, the lungs develop the consistency of liver
(hepatization). Early in hepatization, the gross appearance is
red, and the microscopic morphology comprises alveoli packed
with neutrophils, erythrocytes, and fi brin; fi brous or fi brinopurulent
pleural exudates are common in this phase. Later
in the hepatization phase, the color of the lobe becomes gray
as the fi brinous infl ammatory exudate persists but becomes
devoid of erythrocytes. As the infl ammatory reaction resolves,
the consolidated exudate is digested, leaving a granular semisolid
fl uid to be resorbed. Due to the availability and effi cacy
of antibiotic therapy, lobar pneumonia is now rare.
What is the pattern of consolidation like in bronchopneumonia? What is it like grossly? How does it compare to lobar pneumonia histologically, in the pleura, radiographically?
In bronchopneumonia, the pattern of consolidation is of
noncontiguous airspaces and typically involves more than one lobe with a bronchiolocentric distribution. Grossly, the patches
of consolidation are gray-red to yellow with a surrounding rim
of hyperemia and edema (Fig. 34.4). Histologically, bronchopneumonia
progresses through stages similar to lobar pneumonia
(Fig. 34.3). Pleural involvement in bronchopneumonia is less
common than in lobar pneumonia. Radiographically, bronchopneumonia
is typifi ed by multiple foci of radiopacity.
What is the clinical presentation of lobar and bronchopneumonia like? What is treatment and how effective is it? What are some complications? What is the mortality rate like for patients hospitalized for bacterial pneumonia? What kinds of patients die?
The clinical presentation of lobar pneumonia and of
bronchopneumonia includes malaise, fever, and a productive
cough, occasionally with pleurisy and pleural friction rub.
Appropriate antibiotic therapy (Chap. 35) usually results in
restoration of lung structure and function. Complications include
abscess formation (see below) due to tissue destruction and
necrosis, empyema (Chaps. 26 and 29), organization of the intra-alveolar exudate into solid fi brous tissue [Fig. 34.3(c)],
and dissemination of the infectious organism, possibly leading
to meningitis, arthritis, endocarditis, or sepsis. The mortality
of patients hospitalized for bacterial pneumonia is less than
10%, with death typically related to the development of one of
the aforementioned complications or due to the presence of a signifi cant predisposition like debilitation or chronic alcoholism.
There are numerous etiologies for suppurative bacterial
pneumonia, many of which are briefl y discussed below.
What is the most common cause of lobar pneumonia? What is it like? What else is it the most common cause of? Which of its subtypes causes abscesses?
Streptococcus pneumoniae (previously Pneumococcus
pneumoniae) is a gram-positive coccus; its cocci are typically paired. It is the most common cause of lobar pneumonia. (>90% of cases) and is the most common cause of communityacquired
acute pneumonia (15%-25% of cases). The most
common microbiologic isolates are types 1, 2, 3, and 7. Of
note, S. pneumoniae type 3 also causes lung abscess (see
What is Staph aureus like? What does it typically cause? What else can it cause? What are some risk factors for S. aureus pneumonia?
Staphylococcus aureus is another gram-positive coccus,
but in contrast to the paired cocci of S. pneumoniae, the
cocci of S. aureus are typically in “grapelike” clusters (Fig.
34.5). S. aureus typically causes bronchopneumonia with multiple
abscesses (see below) but can cause lobar pneumonia.
Risk factors for S. aureus pneumonia include recent measles infection in children, recent infl uenza infection in adults, and
intravenous drug abuse.
What is H. influenzae like? What does it cause? What are some possible complications? What are some risk factors?
Haemophilus infl uenzae is a gram-negative coccobacillus
that generally causes bronchopneumonia that notably
in children can be complicated by empyema (Chaps. 26 and 29)
and extrapulmonary infection. Risk factors for H. infl uenzae
pneumonia include recent viral infection, cystic fi brosis,
chronic bronchitis, and bronchiectasis (Chaps. 20, 22, and 38).
What is moraxella catarrhalis like? What does it cause? What are some risk factors?
Moraxella catarrhalis is another gram-negative coccobacillus
that generally causes bronchopneumonia. Risk factors for
M. catarrhalis pneumonia include old age and chronic obstructive
pulmonary disease (Chaps. 20 and 22).
What is Klebsiella pneumoniae like? What does it cause? What is it like clinically? What are some risk factors? What is recovery complicated by? What is the mortality rate like?
Klebsiella pneumoniae is the most common gram-negative
bacillus (rod) causing bacterial pneumonia. The morphology
is that of bronchopneumonia or lobar pneumonia as well as
lung abscess formation (see below). Clinically, K. pneumoniae
pneumonia has an abrupt onset with a cough productive of
gelatinous sputum. Risk factors for K. pneumoniae pneumonia
include debilitation, malnourishment, and alcoholism. Recovery
is often complicated by abscess formation, fi brosis, and/or
bronchiectasis (Chap. 20), and K. pneumoniae pneumonia has
a signifi cant mortality rate, even with therapy.
What is Pseudomonas aeruginosa like? What does it cause? What causes it? What are some risk factors?
aeruginosa, another gram-negative bacillus, typically causes
bronchopneumonia with abscess formation (see below) and,
frequently, empyema (Chaps. 26 and 29). P. aeruginosa pneumonia
is commonly nosocomial, and risk factors include neutropenia,
extensive burn injuries, cystic fi brosis, and mechanical
What is legionella pneumophila like? What does it cause? What are some risk factors? What is its fatality rate?
Legionella pneumophila, the cause of Legionnaire
disease, is a gram-negative bacillus that lives in warm water.
Morphologically, Legionnaire disease is bronchopneumonia.
Risk factors include old age, organ transplantation, and cardiac,
renal, immunologic, or hematologic disease. Legionnaire disease
is fatal in approximately 15% of cases.
What is nocardia asteroides like? What does it cause? In what pts?
Nocardia asteroides is a gram-positive, aerobic, partially
acid-fast, thin, branching, fi lamentous bacterium (Fig. 34.6). It
causes bronchopneumonia with abscess formation (see below),
typically in the setting of an immunocompromised host.
What is Actinomyces israelii like? What does it cause? How does it differ from N. asteroides? What is a common risk factor? What are its colonies like? What are they referred to as? Where are they often found?
Actinomyces israelii, like N. asteroides, is a gram-positive,
thin, branching, fi lamentous bacterium (Fig. 34.7) that causes
bronchopneumonia with abscess formation (see below).
Unlike N. asteroides, however, A. israelii is anaerobic and
is not partially acidfast. A common risk factor for A. israelii
pneumonia is chronic obstructive lung disease. Actinomyces
colonies are yellow, malodorous, and commonly referred to
as sulfur granules, due to their morphologic similarities with
Sulfur granules are commonly seen within tonsillar crypts
in tonsillectomy specimens. Their presence in tonsillar
crypts is responsible in part for persistent malodorous
breath despite teeth brushing and mouthwash usage.
What is aspiration pneumonia? What is its pathogenesis? What are some risk factors?
The fi nal form of acute bacterial pneumonia to be considered
is aspiration pneumonia (Fig. 34.8). It differs from
other forms of bacterial pneumonia in that the pneumonitis is
partly chemical (due to gastric acid injury) and partly bacterial
(typically mixed fl ora of oral cavity residents). Focal necrosis
with subsequent abscess formation (see below) is common
in aspiration pneumonia. Risk factors include acute alcohol
intoxication, coma, anesthesia, sinusitis, gingivo-dental sepsis,
and decreased or absent cough refl ex.
What are various causes of lung abscesses?
As alluded to above, many of the causes of bacterial
pneumonia can also result in the formation of a lung abscess
(Fig. 34.9). Microorganisms typically cultivated from lung
abscess fl uid include aerobic and anaerobic streptococci, Staphylococcus
aureus, many gram-negative microorganisms, and
oral cavity anaerobes (eg, Bacteroides, Fusobacterium, Peptococcus).
The most common cause of lung abscess is aspiration,
but lung abscess can also complicate acute bacterial pneumonia
due to S. aureus, K. pneumoniae, and S. pneumoniae type 3.
Septic embolism, resulting from thrombophlebitis with subsequent embolism or right-sided bacterial endocarditis, can
result in abscess formation, as can traumatic lung injury. Other
settings in which a lung abscess may develop include spread
of an infection from nearby tissue, bronchiectasis (Chap. 20),
and hematogenous seeding; 10%-15% of abscesses are related
to carcinoma (Chap. 31) obstructing an airway
What are the abscesses like in the various etiologies?
can be single or multiple and can affect any part of the lung,
although the specifi c pattern of involvement offers a clue to
the etiology. Aspiration-induced abscesses are usually single
and on the right; abscesses following acute bronchopneumonia
or in the setting of bronchiectasis are usually multiple
and basal; and abscesses secondary to septic embolization or
hematogenous seeding are usually multiple with a haphazard
distribution. Lung abscesses range from a few millimeters in
diameter to several centimeters in greatest dimension
What are the signs/symptoms of abscesses? What are some possible complications?
Symptoms/signs of lung abscess include cough, fever,
copious and malodorous (purulent or sanguineous) sputum,
fever, weight loss, and digital clubbing. Complications of lung
abscess include empyema (Chaps. 26 and 29), hemorrhage,
septic embolization (which can lead to brain abscess or meningitis),
and reactive amyloidosis.
When can fungi infect the lung and produce a suppurative inflamation? What is candida? What inflammation does it produce in the lung?
In the setting of immunocompromise, a few fungi can
infect the lung and induce a suppurative infl ammatory reaction.
Candida species occasionally infect the lung, although esophageal,
vaginal, and cutaneous infections are more common.
The morphology of Candida is budding yeast, frequently with
pseudohyphae (Fig. 34.10). The infl ammatory reaction is typically
suppurative, but occasionally it can be granulomatous.
What are the aspergillus species? What are they like? What is their mechanism of action?
Aspergillus species are angioinvasive molds that frequently
induce thrombosis and infarction with subsequent
suppuration. Morphologically, their hyphae are 5-10 μm wide,
with a rather stiff appearance and a tendency toward 45-degree
branching, a commonly quoted criterion that in reality has little diagnostic value (Fig. 34.11). Hematogenous spread is
common, with involvement of heart valves and brain.
What is mucormycosis? What is it like? What is its mech. of action like ?
A less common fungal infection, mucormycosis (zygomycosis),
is a clinical mimic of aspergillosis. Mucormycosis
can be caused by a number of molds in the Zygomycetes class
including Rhizopus (most common cause), Mucor, Rhizomucor,
Absidia, and Cunninghamella. Like Aspergillus, these fungi are angioinvasive, resulting in thrombosis and infarction
[Fig. 34.12(a), (b)] with subsequent suppurative infl ammation.
The hyphae of the Zygomycetes have few septa (although
they are commonly described as aseptate), are of widely variable
width with a ribbon-like appearance, and have a tendency
toward 90° branching, again, a commonly quoted criterion that
in reality has little diagnostic value [Fig. 34.12(c)
What is infectious interstitial pneumonitis? What causes it? What is it like grossly? What is it like histologically? What is its pathogenesis?
Many viral and a few bacterial pneumonias show an infl ammatory
infi ltrate dominated by interstitial mononuclear cells
rather than the intra-alveolar polymorphonuclear cells that
typify acute bacterial pneumonia. Grossly, infectious interstitial
pneumonitis appears red-blue, congested, and hypocrepitant.
In severe cases, diffuse alveolar damage (Chaps. 23
and 28) may develop. The pathogenesis of infectious interstitial
pneumonitis begins with entry of the microorganism into the
alveolus, where type 1 pneumocytes become infected and
lose their integrity as a membrane, resulting in pulmonary
edema (Chaps. 7 and 26). The proteinaceous edema fl uid and
necrotic cell debris form hyaline membranes, and there is
type 2 pneumocyte hyperplasia. Again, the infl ammatory infi ltrate
is predominantly interstitial and mononuclear, comprising
lymphocytes, plasma cells, and macrophages.
Clinically, what is infectious interstitial pneumonitis called? What is the most common cause? What are risk factors for this ? What other microbes cause it? What else do these microbes usually cause? What can happen in the immunocompromised?
Clinically, infectious interstitial pneumonitis is often
referred to as atypical pneumonia, the most common cause
being Mycoplasma pneumoniae. Risk factors for M. pneumoniae
pneumonia include childhood, adolescence, and life in
closed communities like a school, military camp, or prison.
Other microbes that can cause infectious interstitial pneumonitis
include the bacterium Chlamydia pneumoniae, and numerous viruses (infl uenza, parainfl uenza, RSV, adenovirus, rubeola or
measles, varicella-zoster, and rhinovirus). Most also cause upper
respiratory tract infection with coryza, pharyngitis, laryngitis,
and tracheobronchitis (Chap. 33). In the immunocompromised, cytomegalovirus can cause a life-threatening pneumonitis with interstitial mononuclear infl ammation, focal necrosis, and cells
with characteristic viral inclusions (Fig. 34.14).
WHat is the most common cause of granulomatous infectious pneumonitis? Which microbe causes it? What is this microbe like? What organ does it usually affect? Which organ can it also affect? What is it like morphologically? What is its virulence? What does this have to do with diagnosis?
Tuberculosis (TB) is a communicable granulomatous disease
caused by Mycobacterium tuberculosis (MTB), an acid-fast
bacillus (AFB) (Fig. 34.15), and, though it usually involves
the lung, can affect any organ. Morphologically, the hallmark
of tuberculosis is caseating granulomatous infl ammation
(Fig. 34.16). A granuloma is a circumscribed collection of
epithelioid histiocytes. The term “epithelioid” describes an
increase in cytoplasm, imparting an appearance resembling
squamous epithelial cells. The granulomata in tuberculosis
typically show central necrosis that, at the gross level, has a
cheese-like consistency, referred to as caseous. The virulence
of tuberculosis is largely due to tissue destruction by a hostmediated,
type IV (delayed, cell-mediated) hypersensitivity
reaction. This hypersensitivity is exploited in the purifi ed
protein derivative (PPD) screening test. The clinical course
of tuberculosis is variable and is covered in more detail elsewhere
in this book (Chap. 36).
What percent of people newly infected with MTB develop disease? What is this called? Where do the microbes implant in the lung? How big are the foci or granulomatous consolidation? What is this called? What is the next part of the lung that becomes involved? What are these two parts together called? What are the symptoms of this usually? What happens in 5% of pts. with this? What kind of patients? Describe this process.
Approximately 5% of people newly infected with MTB
develop disease, termed primary tuberculosis. The inhaled
microorganisms implant in distal airspaces of the lower upper
or upper lower lobes; subsequently, a 1-1.5 cm focus of granulomatous
consolidation develops, the Ghon focus. Involvement
of an ipsilateral hilar lymph node follows, and the combination
of the Ghon focus and the involved lymph node is called
the Ghon complex. Primary TB is usually asymptomatic,
with lesions eventually undergoing fi brosis and calcifi cation
(Fig. 34.17). However, approximately 5% of cases of primary
TB, principally among the immunocompromised, show dissemination
to other sites. The lesions in disseminated disease
are often small, the size of millet seeds, a fact that gave rise to the term miliary tuberculosis.
What percent of primary TB cases progress to secondary TB? What is secondary TB? What are the lesions like? Lymph node involvement? What is it like clinically?
Approximately 5%-10% of cases of primary TB progress to secondary tuberculosis. Secondary TB describes reactivation of a dormant primary
infection in a previously infected host. Classically, the lesions in secondary TB are localized to the apex of one or
both lungs, and cavitation of lesions is typical; the lesions are
usually less than 2 cm in greatest dimension and are typically
within 2 cm of the visceral pleura (Fig. 34.18). Lymph node
involvement in secondary TB is less common than in primary
In contrast to primary TB, secondary TB typically
is symptomatic, with insidious gradual systemic signs/symptoms
of malaise, anorexia, weight loss, low-grade fever, night
sweats, and localized symptoms of productive cough, hemoptysis,
and/or pleuritic pain.
What is progressive pulmonary TB like? What is miliary pulmonary TB like? What organs are commonly involved in systemic miliary TB? What other forms of secondary TB are there?
Other forms of secondary TB include progressive pulmonary
TB (fi brocaseous TB), in which the apical lesions
cavitate and there is pleural involvement, leading to serous
pleural effusion, tuberculous empyema, and obliterative
fi brous pleuritis.
Miliary pulmonary TB describes diffuse
involvement of the lung by small (~2 mm) foci of granulomatous
infl ammation with pleural effusion, empyema, or pleuritis.
Endobronchial, endotracheal, and/or laryngeal TB can
Systemic miliary TB most commonly involves
liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, and epididymis.
Isolated organ TB has also been described.
What is histoplasmosis like? What is it similar to clinically and histologically? Where is it endemic to? Where does it live in the environment? What is it like then? How does one become infected? What is it like then?
Histoplasmosis mimics TB clinically and morphologically
(Fig. 34.19). The etiologic agent, Histoplasma capsulatum,
is a dimorphic, nonencapsulated fungus (despite its
name) that is endemic to the Mississippi River Valley and
southeastern United States. The fungus lives as a mold in warm, moist soils enriched by bird or bat droppings. Inhalation
of the spores leads to germination. In contrast to the mold
morphology in the environment, its form at 37°C is that of a yeast that is 2-5 μm in diameter.
What is blastomyces dermatitis like? How does it compare and contrast to Histoplasma capsulatum? What can differentiate it morphologically? What is its inflammation like? What is pseudoepitheliomatous hyperplasia?
Blastomycosis is caused by Blastomyces dermatitis,
another dimorphic fungus endemic to the Mississippi River
Valley and southeastern United States. Like H. capsulatum, B.
dermatitis exists as a mold in the environment and as a yeast
at body temperature [Fig. 34.20 (b)]. However, its yeast form is larger (up to 25 μm) than that of Histoplasma. Morphologically,
a clue that a yeast is in fact Blastomyces is the presence
of broad-based budding [Fig. 34.20 (c)]. The granulomatous
infl ammation of blastomycosis is a bit different than that of
previously mentioned granulomatous pneumonias in that the
granulomata here typically are admixed with a neutrophilic
infl ammatory infi ltrate, referred to as suppurative granulomatous
infl ammation [Fig. 34.20 (a)].
When a focus of
blastomycosis is near an epithelium, that surface may undergo pseudoepitheliomatous hyperplasia, so named because of
its morphologic similarity to squamous cell carcinoma (previously
called squamous cell epithelioma); it can be misdiagnosed
What is coccidioides like? What does it cause? Where is it endemic to?
The third dimorphic fungus that can cause granulomatous
pneumonia is Coccidioides immitis, the etiology of coccidiomycosis
and endemic to the Southwestern and far Western
USA. The granulomatous infl ammation resembles that of
histoplasmosis and contains 20-60 μm nonbudding spherules
often fi lled with endospores (Fig. 34.21).
What fungi can infect the lung of an immunocompromised host? What does it produce? What are the symptoms? What is its virulence? What is it like morphologically?
In the immunocompromised host, Cryptococcus neoformans
can infect the lung and produce a granulomatous infl ammatory
reaction that is typically asymptomatic. Virulence of C. neoformans is primarily related to involvement of the
central nervous system. Morphologically, C. neoformans is a
5-10 μm yeast with a thick halo due to its gelatinous capsule
What is SARS? What is its etiology? What part of the lung does it infect? What else does it infect? What are the symptoms? Timeline? Prognosis? Treatment? Morphology at death?
Severe acute respiratory syndrome (SARS) fi rst appeared
in China in 2002 and subsequently spread to other continents.
Its etiology is a newly discovered coronavirus that
infects the lower respiratory tract (in contrast to most other coronaviruses, which cause approximately one-third of upper
respiratory infections) and subsequently spreads throughout
the body. Following an incubation of 2-10 days, the infected
person develops dry cough, malaise, myalgia, fever, and chills
with less common upper respiratory symptoms. Its pathogenesis
is not well understood. A third of SARS patients improve and resolve the infection; the remainder progress to severe
respiratory distress with dyspnea, tachypnea, and pleurisy.
Therapy is largely supportive, and mortality is approximately
10%. In fatal cases, the morphology of lung involvement is
diffuse alveolar damage (Chaps. 23 and 28) with multinucleated