Transcript pathological

Interstitial Lung Diseases
Dr. C. Lai
Objectives
• Describe the normal interstitium & the pathological
changes in cells & lung architecture that may occur in
interstitial lung disease.
• Describe the key pathological features of the common
idiopathic interstitial lung diseases.
• Describe the pathological features of common secondary
interstitial lung diseases (pneumoconiosis & collagen
vascular disease) & compare & contrast their pathological
features.
• Describe the key pathological features of pulmonary
vascular diseases.
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Air Exchange Diseases
• Infectious pneumonias
• Bacterial, mycobacterial, viral, fungal
• Interstitial lung diseases
• Pneumoconiosis, sarcoidosis, idiopathic interstitial
fibrosis
• Pulmonary “vascular” diseases
• Pulmonary embolism, pulmonary edema, ARDS
Interstitial Lung Diseases
• Pulmonologist, radiologist, & pathologist have
different approaches to ILDs
• Each approach provides unique insight, but can be
confusing due to use of own terminology
• Clinician: disease causing dyspnea, tachypnea, &
restrictive lung disease
• Radiologist: disease producing irregular lines, small
nodules (dots), or ground glass shadows on CXRs
• Pathologist: disease characterized predominantly by
inflammation & fibrosis of pulmonary interstitium
Pulmonary Interstitium
Axial Interstitium
Peripheral Interstitium
Interlobular
Interstitium
Pleural Interstitium
Septal Interstitium
Pathophysiology
• Impaired lung mechanics
• Reduces lung compliance
• Increases work of breathing
• Reduces lung volumes
• Impaired gas exchange
• Smaller lung volumes results in less surface area for gas
exchange
• Interstitial thickening impedes transfer of oxygen from
alveoli to pulmonary capillaries
Interstitial lung diseases
• Acute vs chronic
• Known vs unknown etiology
• Primary vs secondary
• Pathologic patterns
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Interstitial Lung Diseases
• Primary
• Sarcoidosis (20%)
• Idiopathic pulmonary fibrosis - IPF (15%)
• Secondary
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Congestive heart failure/pulmonary edema
Infection (pneumonia)
Malignancy (lymphangitic carcinomatosis)
Pneumoconiosis (25%)
Connective tissue disease (10%)
Hypersensitivity pneumonitis (5%)
Drugs/radiation (5%)
Secondary ILDs
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Pneumoconioses
• Nonneoplastic lung reaction to inhalation of mostly
inorganic particulate matter (mineral dusts) encountered in
the workplace
• Usually fibrogenic:
• Silica
• Asbestos
• Usually non-fibrogenic
• Coal
• Beryllium (granulomatous)
Silicosis
• Common lung disease caused by inhalation of crystalline
proinflammatory silicon dioxide (silica)
• Quartz most commonly implicated
• Subacute presentation (rare)
• Heavy exposure over months to few years
• Intra-alveolar accumulation of lipoproteinaceous material
• Chronic presentation (most common)
• Usually presents after decades of exposure
• Slowly progressive, nodular, fibrosing interstitial lung disease
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Pulmonary Silicosis
• Early stage
• Tiny, barely palpable, discrete pale
to blackened nodules in hilar lymph
nodes & upper lung zones
• Later stage
• Coalescence of nodules into hard,
collagenous scars
• Advanced stage
• Expansion and coalescence of
lesions to produce progressive
massive fibrosis
Silicotic Nodule
• Central area of whorled collagen
fibers (arrow) with peripheral
zone of dust-laden macrophages
• Intra-histiocytic, short, needleshaped, birefringent silicate
particles
• Histiocytic aggregates along
lymphatic routes & within lymph
nodes
Asbestosis
• Asbestos
• Pro-inflammatory crystalline hydrated silicates
• Asbestosis
Asbestos-related disease
Chronic presentation (20 to 30 yrs after first exposure)
Progressive peribronchiolar & alveolar septal fibrosis
Presence of multiple asbestos bodies (long slender fibers
coated by iron, AKA ferruginous bodies)
• Predominantly involves lung bases & subpleural lung
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Asbestos Body
Pulmonary Fibrosis
Septal
thickening
Pleural Plaques
Collagen Vascular Diseases
• Autoimmune diseases can involve the lungs & cause
interstitial pneumonitis at some point in their course
• Rheumatoid arthritis, progressive systemic sclerosis
(scleroderma), systemic lupus erythematosus, Sjögren
syndrome, dermatomyositis-polymyositis, mixed connective
tissue disease
• Histological features are indistinguishable from idiopathic
forms of interstitial lung diseases
• Most have better prognoses than idiopathic pulmonary
fibrosis
Hypersensitivity Pneumonitis
• Immune-mediated interstitial lung disease due to exposure
to inhaled organic antigens
• Thermophilic bacteria, fungi, animal proteins (birds)
• Acute, subacute or chronic presentation
• Peribronchiolar interstitial pneumonitis (centrilobular
lymphoplasmacytic inflammation)
• Presence of poorly-formed, nonnecrotizing granulomas
• Interstitial fibrosis in chronic presentation (late stages)
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Hypersensitivity Pneumonitis
Septal
thickening
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Hypersensitivity Pneumonitis
Giant
cell
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Primary ILDs
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Sarcoidosis
• Systemic granulomatous disease of unknown etiology
• Often involves lung & lymph nodes but can involve many other
tissues & organs
• Immune dysregulation in genetically predisposed individuals
• Type IV hypersensitivity reaction to unidentified antigen with
granulomatous inflammation along lymphatic routes
• Unpredictable clinical course
• 65% to 70% recovery with minimal or no residual sequelae
• 20% permanent loss of some lung function or visual impairment
• 10% to 15% progressive pulmonary fibrosis and cor pulmonale
Sarcoidosis
Granulomata
Interlobular
septum
Sarcoidosis
Artery
Bronchiole
Granulomata
Sarcoidal Granuloma
Histiocytes
Granuloma
Giant cell
Idiopathic Pulmonary Fibrosis
• Clinicopathological syndrome of unknown etiology
characterized by progressive interstitial pulmonary fibrosis &
eventually respiratory failure
• AKA cryptogenic fibrosing alveolitis (Europe)
• Middle aged-to-elderly individuals (rare before 50 yrs old)
• Insidious clinical course with gradually increasing exertional
dyspnea & dry cough
• Median survival is ~3 years after diagnosis
• Lung transplantation is only definitive therapy
Idiopathic Pulmonary Fibrosis
End-Stage Lung
(Honeycombing)
Fibrous septa
Honeycombing
(circled areas)
Idiopathic Pulmonary Fibrosis
Cystic spaces (*)
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Bronchioles
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Septal fibrosis
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Idiopathic Pulmonary Fibrosis
Inflammatory cells
Septal fibrosis
Normal
septum
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Pulmonary Vascular
Diseases
Types of Diseases
• Obstruction to venous outflow (pulmonary congestion )
• Congestive heart failure → pulmonary edema
• Increase in pulmonary artery resistance (pulmonary
hypertension)
• Primary or secondary (e.g. systemic sclerosis)
• Pulmonary artery obstruction (pulmonary
thromboembolism)
• Emboli (common) or thrombosis (uncommon)
• Vascular inflammation (vasculitis)
• Granulomatosis with polyangiitis (Wegener’s granulomatosis),
Churg-Strauss syndrome
Pulmonary Thromboembolism
• Pulmonary artery embolism (common)
• More than 95% associated with deep venous thrombosis of
lower limbs
• Predisposing factors include bedridden, leg surgery, severe
trauma, oral contraceptives, cancer, genetic
hypercoagulability)
• Pulmonary artery thrombosis (uncommon)
• Large vessels: rare, associated with pulmonary hypertension,
pulmonary atherosclerosis, heart failure
• Small vessels: vasculitis, inflammation, diffuse intravascular
coagulation (DIC)
Pulmonary Embolism
• Acute changes
• Luminal obstruction with endothelial damage
• Small vessels: alveolar hemorrhage in corresponding
irrigated area & possible infarct (especially in those with
compromised cardiovascular function)
• Larger vessels: wedge-shaped, hemorrhagic infarction in
center & hemorrhage in periphery
• Chronic changes
• Infarcted areas become fibrotic
• Chronic pulmonary embolism (multiple small emboli) can
lead to pulmonary hypertension and chronic cor pulmonale
Thrombosis
Pulmonary Embolism
Pulmonary Embolism
Embolus
Artery
Respiratory
bronchiole
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Pulmonary Infarct
Infarct
PA thrombus
Pulmonary Infarct
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Alveolar
septa
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Intra-alveolar
hemorrhage (*)
Complete Obstruction
Organized thrombus
Internal elastic layer (short arrows)
Recanalized Thrombus
New lumen
Organized
thrombus
ARDS
• Acute Respiratory Distress Syndrome
• Manifestation of severe acute lung injury (abrupt onset of significant
hypoxemia & bilateral pulmonary infiltrates in absence of heart
failure)
• Diffuse alveolar damage is histologic manifestation of ARDS
• Complication of diverse conditions
• Sepsis, diffuse pulmonary infections, mechanical trauma
(including head injuries), & gastric aspiration account for >50% of
ARDS cases
• Numerous other causes: extensive burns, ionizing radiation, fat
embolism, pancreatitis, inhaled irritants (toxic fumes), chemical
injury, uremia, cardiopulmonary bypass, etc.
Pathogenesis of ARDS
• ARDS initiated by injury to alveolar septal pneumocytes &
endothelial cells
• Endothelial activation from pneumocyte injury or circulating
inflammatory mediators (e.g. sepsis)
• Adhesion & extravasation of neutrophils into interstitium &
alveoli  degranulation & release of more inflammatory
mediators  increased recruitment & adhesion of leukocytes 
more endothelial injury
• Increased vascular permeability  interstitial & intra-alveolar
edema  fibrinous exudate & hyaline membrane formation
• Difficult repair, frequently evolving to death or fibrosis
Diffuse Alveolar Damage
Diffuse Alveolar Damage
Hyaline membranes (small arrows)
Early septal fibrosis