Transcript Document

The Pathology of Lung Diseases
I. RESTRICTIVE LUNG DISEASES
II. OBSTRUCTIVE LUNG DISEASES
I.
RESTRICTIVE LUNG DISEASES
-Diffuse Interstitial Lung Disease
-Infiltrative Lung Disease
-Fibrosing alveolitis
-Honeycomb lung
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Restrictive lung diseases are
characterized by reduced lung volume,
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an alteration in lung parenchyma
a disease of the pleura or chest wall
a disease of neuromuscular apparatus
In physiological terms, restrictive lung
diseases are characterized by
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reduced lung capacity;
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reduced total lung capacity (TLC)
reduced vital capacity
reduced resting lung volume
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The many disorders that cause reduction
or restriction of lung volumes may be
divided into 2 groups based on anatomical
structures:
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1. Intrinsic lung diseases (or diseases of
the lung parenchyma),
2. Extrinsic disorders (or extraparenchymal
diseases).
1.
Intrinsic lung diseases or diseases of the
lung parenchyma:
 The diseases cause inflammation or scarring
of the lung tissue (interstitial lung disease)
or result in filling of the air spaces with
exudate and debris (pneumonitis).
2.
Extrinsic disorders or extraparenchymal
diseases:
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Nonmuscular diseases of the chest wall, and
neuromuscular disorders
The chest wall, pleura, and respiratory muscles are
the components of the respiratory pump, and they
need to function normally for effective ventilation.
If not;
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impaired ventilatory function,
respiratory failure.
RESTRICTIVE LUNG DISEASES
Intrinsic lung diseases
or
Diseases of the lung
parenchyma
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These diseases can be characterized according to
etiological factors:
Acute restrictive pulmonary diseases (acute lung injury)
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Acute Respiratory Distress Syndrome (ARDS)
Acute Hypersensitivity Pneumonitis
Chronic restrictive pulmonary diseases
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Idiopathic fibrotic diseases
Connective tissue diseases
Drug-induced lung disease
Primary diseases of the lungs (including sarcoidosis)
Acute restrictive pulmonary
diseases
Acute Lung Injury
1. Diffuse Alveolar Damage (Acute Respiratory
Distress Syndrome - ARDS)
2. Acute Hypersensitivity Pneumonitis (Extrinsic
Allergic Alveolitis)
1. Diffuse Alveolar Damage (Acute
Respiratory Distress Syndrome - ARDS)
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Diffuse alveolar damage (DAD) refers to a pattern of
reaction to injury of alveolar epithelial and endothelial
cells from a variety of acute insults.
The clinical counterpart of severe DAD is the acute
respiratory distress syndrome (ARDS).
In this disorder, a patient with apparently normal lungs
sustains pulmonary damage and then develops rapidly
progressive respiratory failure.
The condition reflects decreased lung compliance (usually
requiring mechanical ventilation) and hypoxemia and
features extensive radiologic opacities in both lungs
(white-out).
The overall mortality of ARDS is more than 50%, and in
patients older than 60 years, it is as high as 90%.
Nonthoracic Trauma
Shock due to any cause
Fat embolism
Infection
ETIOLOGY:
Important Causes
of the
Acute Respiratory
Distress
Syndrome
Gram-negative septicemia
Other bacterial infections
Viral infections
Aspiration
Near-drowning
Aspiration of gastric contents
Drugs and Therapeutic Agents
Heroin
Oxygen
Radiation
Paraquat
Cytotoxic drugs
Acute Respiratory Distress Syndrome:
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Pathogenesis
Endothelial/capillary injury 
alveolar capillary membrane damage  increased
vascular permeability 
edema (interstitial/alveolar) 
increased synthesis of neutrophil chemotacatic &
activating agents (IL) 
activated neutrophils 
oxidants, proteases, PAF, leukotriens 
tissue damage 
other mediators stimulating collagen production 
Fibrosis
Pathology
Exudative phase (0-7 days):
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congestion,
necrosis of alveolar epithelial cells,
edema,
hemorrhage,
neutrophils in capillaries,
Destruction of type I pneumocytes
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permits exudation of fluid into alveolar spaces, where deposition
of plasma proteins results in formation of fibrin-containing
precipitates (hyaline membranes) on the injured alveolar walls
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congestion
necrosis of alveolar
epithelial cells
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edema
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hemorrhage
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neutrophils in capillaries
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hyaline membranes
If the patient survives the acute phase of ARDS
Proliferative phase (1-3 weeks):
 Proliferation of type II pneumocytes
 Cleaning of remnant hyaline membranes by
pulmonary macrophages
 Expansion of alveolar septa
 Proliferation of fibroblasts
 Collagen tissue production
 Healing or Fibrosing
Fibrosing phase:
 Diffuse interstitial fibrosis
 Honeycomb lung
Proliferation of type II pneumocytes
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Cleaning of remnant hyaline membranes by pulmonary
macrophages
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Expansion of alveolar septa
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Proliferation of fibroblasts
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Diffuse interstitial
fibrosis
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Honeycomb lung.
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2. Acute Hypersensitivity Pneumonitis
(Extrinsic Allergic Alveolitis)
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A response to inhaled antigens
Farmer's lung occurs in farmers exposed to Micropolyspora faeni
from moldy hay
Bagassosis results from exposure to Thermoactinomyces sacchari in
moldy sugar cane
Maple bark-stripper's disease is seen in persons exposed to the
fungus Cryptostroma corticale from moldy maple bark
Bird fancier's lung affects bird keepers with long-term exposure to
proteins from bird feathers, blood and excrement
Hypersensitivity pneumonitis may also be caused by fungi growing
in stagnant water in air conditioners, swimming pools, hot tubs,
and central heating units.
Skin tests and serum precipitating antibodies are often used to
confirm the diagnosis.
In many cases, especially in the chronic form of hypersensitivity
pneumonitis, the inciting antigen is never identified.
Chronic restrictive
pulmonary diseases
CHRONIC INTERSTITIAL
LUNG DISEASES
Characterized by
- decreased lung volume
- decreased oxygen-diffusing capacity on
pulmonary function studies
A large number of pulmonary disorders are grouped as
interstitial, infiltrative, or restrictive diseases
 They are characterized by inflammatory infiltrates in
the interstitial space and have similar clinical and
radiologic presentations
 These diverse maladies
(1) are of known or unknown etiology, and
(2) vary from minimally symptomatic conditions to
severely incapacitating and lethal interstitial fibrosis
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Etiology
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Occupational/environmental diseases (24%)
Sarcoidosis (20%)
Idiopathic pulmonary fibrosis (15%)
Collagen-vascular diseases (8%)
The remainder have more than 100 different causes
and associations.
The most striking findings are;
 Longstanding inflammatory damage
 Fibrosis of the alveolar walls
 Fibrosis finally wipes out groups of alveoli
 Scar contraction of respiratory bronchioles
 The radiographic and autopsy diagnosis of
"honeycomb lung"
ORGANIC DUST EXPOSURE
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Chronic Hypersensitivity Pneumonitis
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Chronic form of Acute Hypersensitivity
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The prototype of hypersensitivity pneumonitis is
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Pneumonitis
farmer's lung
Cause: Inhalation of thermophilic actinomycetes
that grow in moldy hay
Patients with the chronic form of hypersensitivity
pneumonitis have a more nonspecific
presentation, with indolent onset of dyspnea and
cor pulmonale.
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Pathology:
 The main microscopic features of chronic
hypersensitivity pneumonitis include
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bronchiolocentric cellular interstitial pneumonia
noncaseating granulomas (in two thirds of cases)
organizing pneumonia
The bronchiolocentric cellular interstitial infiltrate
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lymphocytes
plasma cells
macrophages
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Patchy mononuclear cell infiltrates,
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Lymphocytes
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Plasma cells
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Epitheloid histiocytes
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Interstitial noncaseating granulomas,
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Interstitial fibrosis.
INORGANIC DUST EXPOSURE
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Pneumoconioses
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Dust inhalation
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Silicosis
Asbestosis
Talcosis
Historically, knife grinder's lung (silicosis).
Mineral dust-induced lung diseases
Coal dust (upper lobe) : Coal workers
 Silica (upper lobe)
: Stone, Ceramics,
Sandblasting
 Asbestos (lower lobe)
: Mining, Milling,
Insulation
: Nuclear energy,
 Beryllium
Aircraft industry
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Particles over 10 µm in diameter deposit on bronchi
and bronchioles and are removed by the mucociliary
escalator.
Smaller particles reach the acinus, and the smallest
ones behave as a gas and are exhaled.
Alveolar macrophages ingest the inhaled particles
and are the primary defenders of the alveolar space.
Most phagocytosed particles ascend to the
mucociliary carpet and are expectorated or
swallowed.
Others migrate into the interstitium of the lung, then
into the lymphatics.
Air particulate exposure
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Pneumoconioses
Pulmonary fibrosis
Asthma
Chronic bronchitis
Lung cancer
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INORGANIC DUST EXPOSURE: Silicosis
 Inhalation of silicon dioxide (silica)
 History: Dyspnea in metal diggers was reported by
Hippocrates
 Early Dutch pathologists wrote that the lungs of
stone cutters sectioned like a mass of sand.
 The major cause of death in workers exposed to
silica dust for the first half of the 20th century
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Sandblasters
Stone cutting
Polishing and sharpening of metals
Ceramic manufacturing
Foundry work
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After their inhalation, silica particles are ingested by
alveolar macrophages
Silicon hydroxide groups on the surface of the
particles form hydrogen bonds with phospholipids
and proteins, an interaction that is presumed to
damage cellular membranes and thereby kill the
macrophages
The dead cells release free silica particles and
fibrogenic factors  progressive massive fibrosis
The released silica is then reingested by
macrophages and the process is amplified
The nodular lesions consist of
concentric layers of hyalinized
collagen
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Surrounded by a dense capsule of
more condensed collagen
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Examination of the nodules by
polarized microscopy reveals the
birefringent silica particles.
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INORGANIC DUST EXPOSURE: Coal
Workers' Pneumoconiosis (CWP)
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Coal dust is composed of amorphous carbon and
other constituents of the earth's surface, including
variable amounts of silica.
Anthracite (hard) coal contains significantly more
quartz
Amorphous carbon by itself is not fibrogenic
Silica is highly fibrogenic, and inhaled anthracotic
particles may thus lead to anthracosilicosis.
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Asymptomatic anthracosis
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Simple CWP:
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Coal macules
Coal nodules
Complicated CWP
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Caplan syndrome
Asymptomatic anthracosis
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CWP
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Coal-dust macules and coal-dust nodules:
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Simple CWP
Complicated CWP (progressive massive fibrosis)
Both are typically multiple and scattered throughout the lung
as 1- to 4-mm black foci
Microscopy
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Coal-dust macule: numerous carbon-laden macrophages
Coal-dust nodule: round or irregular; dust-laden
macrophages associated + fibrotic stroma
Focal dust emphysema
Coal workers’ pneumoconiosis (CWP)
Coal-dust nodule + Focal dust emphysema
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Caplan syndrome
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Rheumatoid nodules (Caplan nodules) in the
lungs of coal miners with rheumatoid arthritis.
Nodular lesions (1-10 cm in diameter)
Multiple, bilateral, and usually peripheral
Microscopy
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Rheumatoid nodule + dust deposits
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Rheumatoid nodules consist of large, central,
necrotic areas surrounded by a border of chronic
inflammation and palisading macrophages.
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INORGANIC DUST EXPOSURE: Asbestosis
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Asbestos - a group of fibrous silicate minerals
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Insulation
Construction materials
Automative brake linings
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Asbestos is a naturally occurring fibrous
silicate that was widely used in the past
for commercial applications because of
its heat-resistance properties.
Geometric forms of asbestos:
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1. Amphibole (straight, stiff, and brittle
fibers).
2. Serpentine (curly and flexible fibers;
90% used in wide-world).
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Asbestos exposure has been industrial or
occupational and primarily affects workers
involved in:
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mining or processing asbestos
shipbuilding
construction
textile
insulation-manufacturing industries
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However, because the latency period between an initial
exposure and the development of most asbestos-related
disease is 20 years or longer,
Asbestos-related disease remains an important public
health issue.
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Exposure to asbestos can cause a number of
thoracic complications
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Asbestosis
Benign pleural effusion
Pleural plaques
Diffuse pleural fibrosis
Rounded atelectasis
Mesothelioma
Lung carcinoma
Asbestos-Related Lung Disease
Pleural lesions
Benign pleural effusion
Parietal pleural plaques
Diffuse pleural fibrosis
Rounded atelectasis
Interstitial lung disease
Asbestosis
Malignant mesothelioma*
Carcinoma of the lung (in smokers)
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ASBESTOSIS
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Asbestosis is diffuse interstitial fibrosis resulting from
inhalation of asbestos fibers
The development of asbestosis requires heavy exposure
to asbestos
Asbestos may produce obstructive as well as restrictive
defects
As the disease progresses, fibrosis spreads beyond the
peribronchiolar location and eventually results in an endstage or (honeycomb) lung
Asbestosis is usually more severe in the lower zones of
the lung
Pathology
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Lower lobes and subpleural
Diffuse pulmonary interstitial fibrosis
Asbestos bodies (golden brown, fusiform or beaded
rods with a translucent center and knobbod ends)
Asbestos fibers coated with an iron-containing
proteinaceous material (ferruginous body)
Lower lobes and subpleural
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Diffuse pulmonary interstitial
fibrosis
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Asbestos fibers coated with an iron-containing proteinaceous material
(ferruginous body)
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Asbestos-Related Lung Disease & Complications
Pleural lesions
Benign pleural effusion
Parietal pleural plaques
Diffuse pleural fibrosis
Rounded atelectasis
Interstitial lung disease
Asbestosis
Progressive fibrosis
Pulmonary hypertension and cor pulmonale
Malignant mesothelioma (80% pleural; 20% peritoneal in origin)
Bronchogenic carcinoma (20-25% of heavily exposed asbestos
worker)
Berryliosis
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Aerospace industry
Dusts/fumes of berrylium
Acute pneumonitis (high doses)
Pulmonary/systemic granulomatous
lesions
Progressively fibrotic lung pathology
Primary or Unclassified diseases
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SARCOIDOSIS
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A granulomatous disease of unknown etiology
Sarcoidosis can involve many systems and organs
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bilateral hilar lymphadenopathy (75-90 %)
lung involvement (90%)
eye and skin lesions
Most sarcoid patients are young adults
Exact pathogenesis of sarcoidosis remains obscure
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T lymphocyte response to exogenous or autologous antigens
These cells accumulate in the affected organs, where they
secrete lymphokines and recruit macrophages, which
participate in the formation of noncaseating granulomas.
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Pathology
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Multiple sarcoid granulomas are scattered in the
interstitium of the lung.
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Frequent bronchial or bronchiolar submucosal infiltration
by sarcoid granulomas accounts for the high diagnostic
yield (<90%) on bronchoscopic biopsy.
The cellular granulomatous phase of sarcoidosis
can progress to a fibrotic phase.
Significant necrosis is usually absent, small foci of
necrosis are seen in one third of open lung
biopsies.
Asteroid bodies (star-shaped crystals)
Schaumann bodies (small calcifications with a
lamellar structure)
Kveim test
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Kveim test, which involves taking
ground-up spleen from someone with
sarcoidosis and injecting it into the
dermis,
If a granuloma forms, the living patient
supposedly has sarcoidosis,
80% sensitive, 95% specific.
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noncaseating granulomas
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Schaumann’s bodies
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asteroid bodies
IDIOPATHIC PULMONARY FIBROSIS
Usual Interstitial Pneumonia (UIP)
 Syn: Chronic interstitial pneumonitis, Interstitial
pneumonitis, Idiopathic pulmonary fibrosis, Cryptogenic
fibrosing alveolitis
 One of the most common types of interstitial pneumonia
 Middle-aged men
 Unknown etiology (?)
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Viral (flu-like illness)
Genetic (familial UIP; UIP-like diseases in neurofibromatosis and
Hermansky-Pudlak syndrome)
Immunologic factors (collagen vascular diseases; autoimmune
disorders)
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Circulating autoantibodies (e.g., antinuclear
antibodies and rheumatoid factor).
Immune complexes (antigen?)
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circulation,
inflamed alveolar walls,
bronchoalveolar-lavage specimens.
Immune complexes  activated alveolar
macrophages  phagocytosis of immune
complexes  release of cytokines 
neutrophil migratrion  damage of alveolar
walls  progression  interstitial fibrosis
Pathology
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The histologic hallmark: patchy chronic
inflammation and interstitial fibrosis
with areas of dense scarring and
honeycomb cystic change
The lungs are small
Fibrosis tends to be worse in the lower
lobes, subpleural regions, and along
interlobular septa
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The honeycomb cystic spaces
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lined by bronchiolar or cuboidal epithelium
contain mucus, macrophages, or
neutrophils
interstitial chronic inflammation
lymphoid aggregates, sometimes
containing germinal centers, in UIP
associated with rheumatoid arthritis
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Vascular changes
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intimal fibrosis
thickening of the media
Progressive fibrosis of lungs  respiratory
insufficiency  pulmonary hypertension 
cor pulmonale  cardiac failure
Desquamative Interstitial Pneumonia (DIP)
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Pathologically described entity
A diffuse lung disease characterized by marked
accumulation of intraalveolar macrophages
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intra-alveolar cells were desquamated epithelial cells,
whereas they are now recognized as macrophages
The macrophages contain a fine golden-brown
pigment.
Alveolar walls show mild thickening by chronic
inflammation and interstitial fibrosis.
Scattered lymphoid aggregates also may be present.
Hyperplasia of type II pneumocytes is often
prominent.
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In cigarette smokers
The radiographic picture of DIP is not specific
but is most frequently described as bilateral
ground glass infiltrates with a lower lobe
predominance
DIP has a much better prognosis than UIP
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Most patients respond well to steroid therapy and
smoking cessation
Collagen-Vascular Diseases & Drugs
and other Treatments
Nonspecific Interstitial Pneumonia (NSIP)
 Etiology
 infection
 collagen vascular disease
 hypersensitivity pneumonitis
 drug reaction, and others)
 or it may be idiopathic.
Pathology
Diffuse uniform changes in the lung
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NSIP
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Cellular type: alveolar septa are diffusely involved
by a mild to moderate lymphcytic infiltrate.
Fibrosing type: septa are diffusely involved by
fibrosis, with or without significant associated
inflammation.