1

Department of General and Clinical Pathology

Medical University - Varna

MODULE 2.
Pulmonary diseases
The Lung: Inflammatory processes
 Learning Objectives
define pulmonary inflammation
know the major cause of these clinical
syndromes and how they are transmitted
describe the various syndromes
know the most common causes of the various
clinical syndromes and what persons are more
likely to get these infections
describe any peculiar signs and identify
etiological agent that causes them

2
 THE LUNG

Inflammatory

Degenerative

Neoplastic

+ diseases of the pleura

3
THE LUNG
WEIGHT
LOBES
SEGMENTS
BRONCHI
ARTERIES,
- pulmonary
- bronchial
VEINS
PLEURA
- visceral
- parietal
NERVES

4
THE LUNG Bronchi
Bronchioles
Terminal
bronchioles
Alveolar ducts
Alveoli
Type 1
pneumocytes
Type 2
pneumocytes
Macrophages
Capillaries 5
6
 Pulmonary Infections
General features

Respiratory tract infections

are the most frequent

Pneumonia can be very broadly defined

as any infection of the lung parenchyma
7
 What is pneumonia?

Pneumonia is an inflammation of the lungs

caused by bacteria, viruses, or chemical irritants
Lobar pneumonia - affects one or more lobes
Bronchial pneumonia (or bronchopneumonia) -
affects patches throughout one or both lungs

8
Pneumonitis
Pulmonitis
Alveolitis

9
How do people "catch pneumonia?"

by breathing in small droplets from the air

when normally present in the upper airways
bacteria or viruses enter the lung
coughing reflex suppressed
immune system weakened
People with recent viral infections, lung and
heart disease, and swallowing problems, as well
as alcoholics, drug users and those who have
suffered a stroke or seizure are at higher risk for
developing pneumonia
10
 Pathogenetic mechanisms
The balance between defense mechanisms
and microbial virulence

Loss or suppression of the cough reflex

Injury to the mucociliary apparatus
Interference with the phagocytic or bactericidal
action of alveolar macrophages by alcohol,
tobacco smoke, anoxia, or oxygen intoxication
Pulmonary congestion and edema
Accumulation of secretions e.g. cystic fibrosis,
bronchial obstruction
11
Pneumonias are classified:
by the specific etiologic agent, which
determines the treatment
by the clinical setting in which the infection
occurs, if no pathogen can be isolated

Classifying by the clinical setting

considerably narrows the list of
suspected pathogens to start
therapy on time
12
 CLINICAL SETTING CLASSIFICATION
Community-Acquired Acute Pneumonia
Streptococcus pneumoniae
Haemophilus influenzae
Moraxella catarrhalis The
Staphylococcus aureus *** Pneumonia
Legionella pneumophila Syndromes
Enterobacteriaceae (Klebsiella pneumoniae) and Pseudomonas spp.
Community-Acquired Atypical Pneumonia
Mycoplasma pneumoniae
Chlamydia spp. (C. pneumoniae, C. psittaci, C. trachomatis)
Coxiella burnetti (Q fever)
Viruses: respiratory syncytial virus, parainfluenza virus (children); influenza A
and B (adults); adenovirus (military recruits); SARS* virus
Nosocomial Pneumonia
Gram-negative rods belonging to Enterobacteriaceae (Klebsiella spp., Serratia
*
marcescens, Escherichia coli) and Pseudomonas spp.

Staphylococcus aureus (usually penicillin-resistant) *** 13

 CLINICAL SETTING CLASSIFICATION

Aspiration Pneumonia
Anaerobic oral flora (Bacteroides, Prevotella, Fusobacterium,
Peptostreptococcus), admixed with aerobic bacteria
(Streptococcus pneumoniae, Staphylococcus aureus,
Haemophilas influenzae, and Pseudomonas aeruginosa)
Chronic Pneumonia
The
Pneumonia
Nocardia
Actinomyces
Syndromes
Granulomatous: Mycobacterium tuberculosis and atypical mycobacteria,
Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis
Necrotizing Pneumonia and Lung Abscess
Anaerobic bacteria (extremely common), with or without mixed aerobic infection
Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pyogenes, and
type 3 pneumococcus (uncommon)
*
14
 COMMUNITY-ACQUIRED
ACUTE PNEUMONIAS

may be bacterial or viral

alveoli are filled with an inflammatory
exudate consolidation ("solidification")
of the pulmonary tissue
Predisposing conditions include extremes
of age, chronic diseases

15
 COMMUNITY-ACQUIRED
ACUTE PNEUMONIAS

Streptococcus pneumoniae - most common cause

Gram-stained sputum - numerous neutrophils with
the typical Gram-positive, lancet-shaped diplococci
S. pneumoniae - endogenous flora in 20% of adults

16
Streptococcus Pneumoniae

17
 COMMUNITY-ACQUIRED
ACUTE PNEUMONIAS
Legionella Pneumophila
Legionnaires disease

a motile, rod-shaped,
gram-negative,
aerobic bacterium
18
 COMMUNITY-ACQUIRED
ACUTE PNEUMONIAS

Legionella Pneumophila
Legionnaires disease

considered a "facultative parasite

in the last twenty years identified as the leading
cause of Legionnaire's Disease
LD - first discovered in 1976 among a group
of elderly men attending an American Legion
Convention in Philadelphia, Pennsylvania
19
Legionella
Pneumophila
20
 Legionella
Pneumophila

Dg - demonstration of Legionella antigens in the urine

or a positive fluorescent antibody test on sputum
samples; culture remains the gold standard
21
COMMUNITY-ACQUIRED ACUTE PNEUMONIA

H. influenzae pneumonia
follows viral respiratory infections
pediatric emergency with high mortality rate
descending laryngotracheobronchitis results in
airway obstruction
the smaller bronchi are plugged by dense,
fibrin-rich exudate of PMN
Gross - pulmonary consolidation is usually
lobular and patchy but may be confluent and
involve the entire lung lobe
22
 COMMUNITY-ACQUIRED
ACUTE PNEUMONIAS

Moraxella Catarrhalis

bacterial pneumonia, especially in the elderly

the second most common cause of acute
exacerbation of COPD, after H.influenzae
Along with S. pneumoniae and H. influenzae,
M. catarrhalis causes otitis media in children

23
COMMUNITY-ACQUIRED
AND NOSOCOMIAL

Staphylococcal
pneumonia

an abscess in the upper lobe

beneath the pleura
24
 Staphylococcus Aureus

an important cause of secondary bacterial

pneumonia in children and healthy adults
high incidence of lung abscess and empyema
intravenous drug abusers
- at high risk + associated endocarditis

25
 NOSOCOMIAL PNEUMONIAE

Pseudomonas Aeruginosa
most common in the group
occurs in cystic fibrosis patients
common in neutropenic patients
has a propensity to invade blood vessels with
consequent extrapulmonary spread
Pseudomonas septicemia = very fulminant

26
NOSOCOMIAL PNEUMONIAE

Pseudomonas Aeruginosa

27
Klebsiella
Pneumoniae

28
 Klebsiella Pneumoniae

the most frequent of Gram-negative pneumonia

debilitated and malnourished people, particularly
chronic alcoholics
thick and gelatinous sputum is characteristic
because the organism produces an abundant viscid
capsular polysaccharide

29
 Bronchial pneumonia (or bronchopneumonia) -
affects patches throughout the lung

Lobar -
affects one or more
lobes of the lung
30
Lobar pneumonia Bronchopneumonia
31
 often difficult to apply in the individual case
because patterns overlap
Most important is identification of the
causative agent and determination of the
extent of disease

32
LOBAR PNEUMONIA - four stages :
congestion
red hepatization
gray hepatization
resolution
++Pleural fibrinous reaction (pleuritis), may
similarly resolve or if undergoes organization,
fibrous thickening or permanent adhesions
++CARNIFICATION - organization in alveoli

33
BRONCHOPNEUMONIA
consolidated areas of acute suppuration
may be patchy through one lobe, often
multilobar and bilateral - and basal because
secretions gravitate into the lower lobes
Well-developed lesions are usually 3 - 4 cm,
slightly elevated, dry, granular, gray-red to
yellow, and poorly delimited at their margins
affected areas are red-blue, congested, and
subcrepitant
the pleura is smooth, and pleuritis or pleural
effusions are infrequent
34
 BRONCHOPNEUMONIA

suppurative, neutrophil-rich
exudate that fills the
bronchi, bronchioles, and
adjacent alveolar spaces

35
BRONCHOPNEUMONIA

36
BRONCHOPNEUMONIA
- Complications include:
(1) tissue destruction and necrosis
abscess formation
(2) spread to the pleural cavity empyema
(3) organization of the exudate
(4) bacteremic dissemination to the heart valves,
pericardium, brain, kidneys, spleen, or joints,
causing metastatic abscesses, endocarditis,
meningitis, or suppurative arthritis
37
 COMMUNITY-ACQUIRED
ATYPICAL (VIRAL AND
MYCOPLASMAL) PNEUMONIAS

"primary atypical pneumonia" - initially applied to

an acute febrile respiratory disease
patchy inflammation, largely confined to the septa
and interstitium
The term "atypical" denotes
moderate amount of sputum
no physical findings of consolidation
only moderate elevation of white cell count
lack of alveolar exudate
38
ATYPICAL (VIRAL & MYCOPLASMAL) PNEUMONIAS

Etiology -most common Mycoplasma pneumoniae

- particularly among children and young adults
+ influenza virus types A and B, the RSV,
adenovirus, rhinoviruses, rubeola, and varicella
+ C. pneumoniae; and Coxiella burnetti (Q fever)
Any one of these cause merely an upper
respiratory tract infection (the common cold),
or a more severe lower respiratory tract infection
Common in malnutrition, alcoholism, and
underlying debilitating illnesses 39
COMMUNITY-ACQUIRED ATYPICAL (VIRAL
AND MYCOPLASMAL) PNEUMONIAS

The common pathogenetic mechanism -

attachment to the respiratory epithelium,
necrosis and an inflammatory response
in the alveoli - usually interstitial inflammation,
and some fluid
Damage to and denudation of the respiratory
epithelium inhibit mucociliary clearance and
predispose to secondary bacterial infections

40
 Morphology histologic pattern
interstitial inflammation within alveoli walls
septa - widened and edematous, with mononuclears
- lymphocytes, histiocytes, and some plasma cells
in acute cases - neutrophils may also be present
alveoli - free from exudate, but may contain protein
material, and the typical pink hyaline membranes

These changes reflect alveolar damage

similar to that seen diffusely in ARDS
Eradication of the infection is followed by
reconstitution of the normal lung architecture
41
 Morphology histologic pattern

Superimposed bacterial infection modifies the

picture by causing ulcerative bronchitis and
bronchiolitis
Some viruses - HSV, varicella, adenovirus,
may be associated with necrosis of bronchial
and alveolar epithelium and acute inflammation
CMV - epithelial giant cells with intranuclear
or intracytoplasmic inclusions
Other viruses produce cytopathic changes

42
 Influenza Infections

general features

The genome - eight helices of single-stranded RNA,

*
each encoding a single gene and each bound by a
nucleoprotein that determines the type of influenza
virus (A, B, or C)
viral hemagglutinin and neuraminidase, determine the
subtype of the virus (H1 to H3; N1 or N2)
Host antibodies to the hemagglutinin and neuraminidase
prevent and ameliorate, respectively, future infection

43
 Influenza Infections

Two mechanisms account for the clearance of

primary influenza virus infection:
cytotoxic T cells kill virus-infected cells
an intracellular anti-influenza protein (called Mx1)
is induced in macrophages by interferon- and -
Epidemics of influenza occur through mutations
of the hemagglutinin and neuraminidase that
allow the virus to escape most host antibodies
(antigenic drift)

44
 Viral upper respiratory infections
Morphology

mucosal hyperemia and swelling

predominantly lymphomonocytic and
plasmacytic infiltration of the submucosa
overproduction of mucus secretions
The swollen mucosa and viscid exudate may
plug the nasal channels, sinuses, or the
Eustachian tubes and lead to suppurative
secondary bacterial infection

45
 Viral upper respiratory infections
Morphology
Virus-induced tonsillitis - the Waldeyer ring
Laryngotracheo+bronchitis - vocal cord swelling,
abundant mucous exudation and lung atelectasis,
due to plugging of small airways
Bronchiolitis - more severe infection
- widespread plugging of secondary and terminal
airways by cell debris, fibrin, and exudate
- when prolonged - organization and fibrosis, result
in obliterative bronchiolitis and permanent lung
damage +viral pneumonia
46
 Acute Respiratory Syndrome

The severe acute respiratory syndrome (SARS)

first appeared in 2002 in China
there were more than 8000 cases (774 deaths)
After an incubation period of 2-10 days, SARS
begins with a dry cough, malaise, myalgias,
fever and chills, less commonly - sore throat
2/3 of patients progress to SARS disease with
dyspnea, tachypnea, and pleurisy and nearly
10% of patients die
47
SARS

48
Acute Respiratory Syndrome

SARS
The cause is a previously
undiscovered coronavirus,
which differs from
previously known strains in
that it infects the lower
respiratory tract and spreads
throughout the body 49
 SARS diagnosis

detection of the virus by PCR

detection of antibodies to the virus
Coronaviruses can be seen within
pneumocytes by electron microscopy

50
SARS
morphology

diffuse alveolar damage

and multinucleated giant cells
51
scattered type II pneumocytes
with marked cytologic
changes +multinucleation,
cytomegaly, nucleomegaly,
clearing ofchromatin, and
prominent nucleoli

Diffuse alveolar
damage (DAD)
52
 SARS
histology

Early exudative phase

diffuse alveolar damage,
vascular congestion, with
interstitial and airspace
edema and inflammatory
cell infiltrates
53
 SARS
histology

exudative phase
diffuse alveolar
damage, with
hyaline membranes

54
SARS histology

organizing phase
diffuse alveolar
damage

55
 NOSOCOMIAL PNEUMONIA

defined as pulmonary infections acquired in

the course of a hospital stay
common in patients with immunosuppression,
prolonged antibiotic therapy, on mechanical
ventilation or intravascular catheters
Gram-negative rods (Enterobacteriaceae and
Pseudomonas species) and Staphylococcus
aureus are the most common isolates

56
 ASPIRATION PNEUMONIA

in markedly debilitated patients

those who aspirate gastric contents while
unconscious or during vomiting
the resultant pneumonia is partly chemical,
owing to the gastric acid, and partly bacterial
typically, more than one organism is involved
this pneumonia is often necrotizing, with a
fulminant clinical course, and is a frequent cause
of death
57
 LUNG ABSCESS

a local suppurative process within the lung,

characterized by necrosis of lung tissue
mixed infections occur often
aerobic and anaerobic organisms - streptococci,
St. aureus, and a host of Gram (-) organisms

58
LUNG ABSCESS causative mechanisms:
aspiration of infective material and gastric
content - in alcoholics, coma, sinobronchial
infections, anesthesia, debilitation, sinusitis,
oropharyngeal surgical procedures
antecedent primary bacterial infection
bronchiectasis
septic embolism and hematogenous seeding
neoplasia
direct traumatic penetrations
spread of infection from a neighboring organ
primary cryptogenic lung abscesses 59
 LUNG ABSCESS
Morphology

diameter - a few millimeters

to cavities of 5-6 cm
when due to aspiration are
more common on the right
and are most often single

60
Abscesses that develop in
the course of pneumonia
or bronchiectasis are usually
multiple, basal, and diffusely
scattered
Septic emboli and pyemic
abscesses, are multiple, smaller
and may affect any region

LUNG
ABSCESS
Morphology
61
 LUNG ABSCESS
Morphology

The abscess cavity might

be filled with suppurative
debris, or partially empty
if drained through
the air passages

62
 LUNG ABSCESS
Morphology

The cardinal histologic change - suppurative

destruction of the parenchyma with central area of
cavitation and peripheral pyogenic membrane
Continued infection leads to large, green-black,
multilocular cavities with poor demarcation of
their margins - gangrene of the lung
With time, considerable fibroblastic proliferation
produces a fibrous wall - chronic abscess

63
 Chronic pneumonia
Definition - chronic inflammatory process in lung
parenchyma
most often a localized lesion in the
immunocompetent patient, with or without
regional lymph node involvement
May be due to infectious and noninfectious
reasons
There is granulomatous inflammation, which may
be due to bacteria (M. tuberculosis) or fungi

64
 Chronic pneumonia
characteristic features:
collection of chronic
inflammatory cells
destruction - normal
alveoli are replaced
by spaces lined by
cuboidal epithelium
replacement by
connective tissue

65
66
 Chronic pneumonia
pulmonary mycoses
Histoplasmosis, blastomycosis, and
coccidioidomycosis
granulomatous diseases that may resemble
tuberculosis
caused by fungi that are thermally dimorphic in
that they grow as hyphae that produce spores at
environmental temperatures but grow as yeasts
(spherules or ellipses) at body temperature
Fungi show geographic distribution
67
 Histoplasmosis

Histoplasma capsulatum infection is acquired

by inhalation of dust particles from soil
contaminated with bird or bat droppings that
contain small spores (microconidia)

68
 Histoplasmosis features
intracellular parasite of macrophages
clinical signs and morphology resemble TB
a self-limited and often latent primary pulmonary
involvement, which may result in coin lesions
chronic, progressive, secondary lung disease,
which is localized to the lung apices
extrapulmonary lesions - mediastinum, adrenals,
liver, or meninges
a widely disseminated involvement, particularly
in immunosuppressed patients
69
 Histoplasmosis pathogenesis

H. capsulatum - enters macrophages after

opsonization
or by a distinct mechanism that appears unique to
this fungus - expresses HSP60 on the surface
that binds to 2 integrins on macrophageal surface
Histoplasma yeasts so phagocytosed by the
unstimulated macrophages, multiply within the
phagolysosome, and lyse the host cells
Lacking cellular immunity, AIDS patients are
susceptible to disseminated infection
70
 Histoplasmosis Morphology

epithelioid cell granulomas, which usually

undergo coagulative necrosis and coalesce to
produce large areas of consolidation but may
also liquefy to form cavities
With spontaneous or drug control, the lesions
undergo fibrosis and concentric calcification
(tree-bark appearance)
Histologic identification of the 3-5m thin-
walled yeast forms (methenamine silver stain)
that may persist in tissues for years
71
Histoplasma capsulatum yeast
forms fill phagocytes in a
lymph node of a patient with
disseminated histoplasmosis
72
 Histoplasmosis Morphology

chronic - gray-white granulomas in lung apices

with involvement of the pleura and hilar nodes
further progression -more and more of the lung
parenchyma, with cavity formation less frequent
than in tuberculosis
fulminant disseminated - in immunosuppression,
granulomas are not formed
focal accumulations of mononuclear phagocytes
filled with fungal yeasts throughout the tissues

73
 Histoplasmosis

Numerous yeast
forms of Histoplasma
capsulatum in
alveolar macrophages
74
 Blastomyces dermatidis

soil-inhabiting, dimorphic fungus

three clinical forms:
pulmonary blastomycosis
disseminated blastomycosis
a rare primary cutaneous form that results from
direct inoculation of organisms into the skin

75
 Pulmonary blastomycosis

an abrupt illness with productive cough,

headache, chest pain, weight loss, fever, night
sweats, abdominal pain, chills, and anorexia
Chest X-ray - lobar consolidation, multilobar
and perihilar infiltrates, multiple nodules, or
miliary infiltrates
The upper lobes - most frequently involved
may resolve spontaneously, persist, or
progress to a chronic lesion

76
 Blastomycosis
Morphology

Involvement of the skin

and larynx - marked
epithelial hyperplasia,
similar to
squamous cell Ca 77
 Blastomycosis
Morphology

Note the characteristic thick

wall and nuclei
(not seen in other fungi)

lung lesions - suppurative granulomas; rounded

budding yeasts, larger than neutrophils
78
 Blastomycosis

Silver
stain

B. dermatidis is a round, 5-15 m yeast cell that

divides by broad-based budding
a thick, double-contour cell wall and multiple nuclei
79