Transcript asbestos fiber microscope

RESTRICTIVE LUNG DISEASES
Interstitial Lung Diseases
LECTURE GOALS:
Restrictive lung disease
1&2
(Pathology)
1. Define restrictive lung disease.
2. Be familiar with the principles, cause & mechanisms in
acute restrictive lung disease identifying Acute
Respiratory Distress Syndrome in adults and newborn.
3. Discuss the pathology of idiopathic pulmonary fibrosis.
4. List the commoner cause of pulmonary fibrosis with
emphasis on the pathology of Sarcoidosis.
5. Be familiar with causes and pathology of
pneumoconiosis.
6. Identify causes and pathology of Asbestosis &
Mesothalioma.
7. List the pulmonary hemorrhage syndromes, which may
lead to pulmonary fibrosis.
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Include diseases which interfere with lung expansion.
Chest wall defects & severe obesity.
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Pulmonary diseases .
Restrictive Pulmonary diseases Stiff non
compliant lung  Dyspnea & Hypoxia.
Destruction of alveolar walls with
FIBROSIS in the chronic phase.
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Kyphosis/Scoliosis
Restrictive pulmonary diseases :
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Predominantly diffuse.
Acute or chronic.
Acute is represented by ARDS.
Chronic is involvement of the pulmonary
connective tissue  FIBROSIS.
Principally involves the alveolar walls.
PATHOGENESIS : Alveolar septae structure
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Pulmonary Function Tests :
  Forced Vital Capacity ( FVC ) and ( FEV1 )
in the same ratio.
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 FEV1 / FVC near normal in Restrictive
lung diseases.
Characteristics :
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Decreased lung compliance (stiff lung).
Increase in effort to breath → (inspiratory dyspnea).
Damage to alveolar epithelium & vasculature leads to
abnormalities in ventilation- perfusion ratio &
hypoxemia.
X-ray : Bilateral diffuse pulmonary infiltrates.
Progression to respiratory failure, Pulmonary
hypertension, ± Honey Comb Lung
LATER stage of ARDS:
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Macrophage derived fibrogenic factors
( TGF-B , PDGF, IL-1, TNF)
Recruitment of fibroblasts →
Fibrogenesis
All previous can be counteracted by endogenous antiproteases, antioxidants,
& anti - inflammatory cytokines(IL-10) Clotting cascade is also triggered
Pathogenesis :
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Whatever the cause, the lesion is an
‘alveolitis’
Lymphocytes, macrophages & neutrophils
Macrophage activation→ leukotrines
recruit neutrophils & Fibrogenic Cytokines
induce FIBROSIS.
Major types of Interstitial Lung
Diseases with different patterns :
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Fibrosing:
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Idiopathic Pulmonary Fibrosis (UIP)
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Nonspecific Interstitial Pneumonia
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Cryptogenic Organizing Pneumonia
( BOOP )
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Associated with Collagen Vascular Dis.
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Pneumoconiosis
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Drug Related & Radiation Induced
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Granulomatous :
 Sarcoidosis
 Hypersensitivity Pneumonitis
Eosinophilic :
 Pulmonary Eosinophilia
Smoking Related
Fibrosing Reaction
1- Idiopathic Pulmonary Fibrosis :
(Cryptogenic Fibrosing Alveolitis)
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M  F.
Two thirds of patients are older than 60
years of age at presentation.
Diagnosed only after exclusion of all other
causes.
Severe hypoxemia & cyanosis.
Histological pattern of Usual Interstitial
Pneumonia ( UIP)
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IPF is caused by “repeated cycles” of epithelial
activation/injury by unknown causes until now.
Inflammation by many cell types will lead to initiate the
process of healing, but in IPF instead of complete healing,
there will be activation of macrophages  which will
initiate fibrosis.
Clinical Features & Examination :
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Insidious presentation
Nonproductive cough & progressive dyspnea
Examination :
 Cyanosis, clubbing , dry ‘crackles’ at
inspiration
 Chest X ray  bilateral basal nodular infiltrates
 Pulmonary function tests  restrictive result
 Lung biopsy ± Bronchoalveolar lavage
Prognosis : Death in 2-4 years
Morphology :
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Cobblestones because of the retraction of scars
along the interlobular septa.
Interstitial chronic inflammation with cellular
fibroblastic proliferation OR
Interstitial collagenous acellular process
- Not all areas affected equally:
‘Temporal heterogeneity’.
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Peripheral location, basal, along pleura &
septae.
- Patchy fibrosis collapse alveolar walls 
irregular cystic spaces lined by hyperplastic
type II pneumocytes or bronchiolar lining
(Honeycomb Lung).
Cobblestone Appearance
2- Nonspecific Interstitial Pneumonia:
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Similar to previous, but more diffuse &
without heterogeneity
Better prognosis than UIP.
WASTEBASKET DIAGNOSIS, of ANY
pneumonia (pneumonitis) of any known or
unknown etiology.
 Mature FIBROSING Pattern *
 CELLULAR Pattern : INFILTRATE (LYMPHS
& PLASMA CELLS)
3 -Cryptogenic Organizing Pneumonia :
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Bronchiolitis Obliterans Organizing Pneumonia
(BOOP)
Many causes (inflammatory, vascular…)
but mainly cryptogenic
Interstitial inflammation ,not temporal
heterogeneity.
Polypoid plugs of fibrosis in bronchioles &
alveolar ducts & alveoli
No destruction of lung architecture
Recovery within 6 months with steroids
BOOP
4- “COLLAGEN” VASCULAR DISEASES
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Rheumatoid Arthritis
SLE (“Lupus”)
Progressive Systemic Sclerosis
(Scleroderma)
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Any interstitial pattern
5- Pneumoconiosis :
Environmental /occupational diseases
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Pneumoconiosis is a term originally coined to describe the nonneoplastic lung reaction to inhalation of mineral dusts.
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The three most common forms of pneumoconiosis result from
exposure to coal dust, silica, and asbestos—nearly always result
from exposure in the workplace.
The reaction of the lung to mineral dusts depends on many
variables, including size, shape, solubility, and reactivity of the
particles.
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Particles that are 1 to 5 μm in diameter are the most dangerous,
because they get lodged at the bifurcation of the distal airways.
The pulmonary alveolar macrophage is a key cellular element in
the initiation and perpetuation of lung injury and fibrosis.
Tobacco smoking worsens the effects of all inhaled mineral dusts,
more so with asbestos than with any other particle.
A- Anthracosis ( Coal miner’s lung)
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Pulmonary anthracosis is the most common pattern of
Coal related diseases.
Seen in tobacco smokers.
Inhaled carbon pigment is engulfed by macrophages, which
then accumulate in the connective tissue.
1- Simple CWP: macule and nodule.
1- The coal macule consists of dust-laden macrophages.
2- The coal nodule is larger and contains collagen.
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Upper lobes involved more than lower lobe.
Centrilobular emphysema might occur.
**CWP: Coal Workers pneumoconiosis.
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2- Complicated CWP :
Occurs on a background of simple CWP by coalescence of coal
nodules. 2-10 cm.
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Requires many years to develop.
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3- Progressive Massive Fibrosis:increasing pulmonary dysfunction,
pulmonary hypertension, and cor pulmonale.
No increase in risk for lung cancer.
Anthracosis with Fibrosis
B- Silicosis
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Commonest occupational lung disease
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Inhalation of crystalline silica (Quartz: most
common) & amorphous types.
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Workers in sandblasting ,ceramics , glass and
stone cutting, construction….etc
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Acute heavy exposure  ARDS
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Chronic after 20-40 yrs exposure
Pathogenesis :
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Silica in macrophages  injury to cell membrane.
Release silica +fibroblast stimulating factor .
Free silica re-engulfed in macrophages .
The cycle is repeated  Progressive Fibrosis
Pathology :
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Silicotic small nodules (2-4 mm),in upper lobe.
Later large nodules (1-10cm) silicotic nodule demonstrates
concentrically arranged hyalinized collagen fibers
surrounding an amorphous acellular center.
Examination of the nodules by polarized microscopy
reveals weakly birefringent silica particles, primarily in
the center of the nodules
Fibrotic calcified nodules in hilar lymph nodes →X ray : Egg
shell calcification
Progressive Massive Fibrosis & Honey comb
Clinical picture :
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Many patients are asymptomatic.
Most patients do not develop shortness of breath until late in
the course, after PMF is present.
Shortening of breath
Silicosis is associated with an increased susceptibility
to tuberculosis.
 risk lung cancer with crystalline silica.
Silicotic Nodule: concentrically arranged hyalinized
collagen fibers surrounding an amorphous acellular
center
C-Asbestos induced lesions
 Workers in installation & insulation materials, ship
builders………
 Family members also at risk.
 Long latency ( 10-20 yrs.)
 Two forms of asbestos :
 Most common: Serpentine ~ ʅ Ϛ
 Amphibole : straight & stiff
 Asbestos Bodies
(Ferruginous Bodies)
 Found in sputum & bronchial wash &
lung tissue , composed of :
Asbestos fibers + protein + iron
( positive Perl’s stain)
 May be even in normal !
Asbestos body in macrophage
Ferruginous Asbestos Body
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Lesions include :
1- Asbestosis : chronic diffuse interstital
fibrosis lower lobe  Honey comb lung
& cor pulmonale
2- Pleural effusion
3- Pleural fibrosis
4- Pleural plaques most common & parietal
pleura
5- Malignant Mesothelioma
6-  risk lung CA ,larynx , stomach & colon
Pleural Plaques
6- Drug & Radiation Induced Pulmonary
Diseases
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Cancer Chemotherapy (Bleomycine)
Anti-arrythmic agents (amiodarone)
Radiation pneumonitis mainly
anticancer:
 Acute or chronic
Granulomatous Reaction :
1- Sarcoidosis :
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 in US blacks, Scandinavians and
nonsmokers
Multisystem disorder
 Lungs & hilar LNs
 Skin
 Eye & lacrimal glands
 Salivary glands
 Liver, Spleen, Bone marrow
Adults younger than 40 years
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Etiology :
 Disordered immune response
 Genetic predisposition (HLA-A1 &
HLA-B8)
 Environmental antigen ???
 Atypical mycobacteria
 Pollen
 Virus
Immune mechanisms :
 Type IV hypersensitivity reaction
 T lymphocytes subsets abnormalities
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- Oligoclonal expansion of T cell
subsets
- Blood :  CD4 /CD8 ( NR 0.9- 2.5).
- Alveolar lavage : T- cells.
-  level IL-8, TNF, MIP-1 locally
Polyclonal hypergammaglobulinemia
Pathology :
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Lesions are noncaseating granulomas with giant
cells containing Schaumann & Asteroid bodies (not
specific)
Lymph nodes 75-90% hilar, 30%peripheral
Lung : 90%Interstitium, parabronchioles,
paravenules and pleura.
5-15% progress to honey comb lung
Spleen, liver, BM : often involved without
organ enlargment .
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Skin, eyes, lacrimal & salivary glands
Occular involvement + Lacrimal Gland=
 SICCA Syndrome
+ Parotid involvement =
 MIKULICZ Syndrome
Sarcoid Granuloma
Schaumann Bodies
NON-Caseating Granulomas are the RULE
“Asteroid” bodies within these granulomas are virtually diagnostic
Clinical picture :
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May be asymptomatic or insidious onset
of fever, malaise, cough & dyspnea
Majority recover ( ± steroid therapy )
20% have respiratory dysfunction
10 - 15% progress to interstitial fibrosis
Some patients may have additional
obstructive symptoms
Diagnosis:
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By exclusion of all other granulomas
Radiological picture :
Bilateral hilar lymphadenopathy
Ground glass miliary shadows in both lung
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Hypercalcemia
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Skin test : KVEIM test
2- Hypersensitivity Pneumonitis :
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Syndrome caused by a variety of inhaled
organic dust or chemicals
Inflammatory response in alveoli &
terminal bronchioles, accompanied by
systemic symptoms
Type III & type IV reactions.
Presentation depends on duration &
intensity of exposure :
- Acute
- Subacute
- Chronic
Hypersensitivity pneumonitis
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Immunologically mediated disorder
affecting airways and interstitium.
Farmer’s lung
Thermophilic actinomycetes in hay
Pigeon Air-condition lung
breeder’s Thermophilic bacteria
Phases of Hypersensitivity Pneumonitis
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Acute : direct irritant effect  asthmatic
attack with dyspnea, fever,…4-8 hr. after
exposure
Chronic : delayed hypersensitivity reaction .
Morphology in chronic cases :
Patchy interstitial inflammatory infiltrate in
terminal bronchioles & alveolar walls
75% show noncaseating granuloma in
alveolar walls in peribronchial t. FIBROSIS
Extrinsic allergic alveolitis with granuloma
Smoking –Related Interstitial Diseases
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Desquamative Interstitial Pneumonia(DIP)
 Interstitial inflammation + macrophages
in alveolar spaces
 Respond to steroids
Bronchiolocentric respiratory bronchiolitis
with peribrochial fibrosis