Pathology of Restrictive Lung Diseases Flashcards
restrictive lung diseases - general principles
*disorders characterized by inflammation and fibrosis of lung interstitium
*stiff lungs → reduced diffusion capacity, lung volume, lung compliance
*damage to alveolar epithelium and interstitial vasculature
*PFTs: decreased TLC, normal FEV1/FVC
major restrictive lung diseases
- idiopathic pulmonary fibrosis (IPF)
- sarcoidosis
- hypersensitivity pneumonitis
- pneumoconioses
clinical features of restrictive lung diseases
*dyspnea, tachypnea, end-inspiratory crackles
*usually no wheezing or other evidence of airway obstruction
*eventual cyanosis
*eventually, secondary pulmonary hypertension → cor pulmonale
“honeycombing” of lungs on CT scan
idiopathic pulmonary fibrosis (IPF) - overview
*clinicopathologic syndrome of unknown etiology marked by PROGRESSIVE INTERSTITIAL FIBROSIS and respiratory failure
idiopathic pulmonary fibrosis (IPF) - pathogenesis
*? repeated injury and defective repair of alveolar epithelium, leading to interstitial fibrosis
*may involve multiple cycles of lung injury, inflammation, and fibrosis
*associated with tobacco smoking, environmental pollutants, and genetic defects
idiopathic pulmonary fibrosis (IPF) - genetic alterations
*telomerase loss-of-function mutations
*mucin (MUC5B) altered production
*surfactant germline mutations
idiopathic pulmonary fibrosis (IPF) - gross morphology
*“cobblestoned” pleural surface
*firm/rubbery white fibrosis
idiopathic pulmonary fibrosis (IPF) - microscopic morphology
*patchy fibrosis
*replacement of elastin with collagen
*collapse of alveolar walls and formation of cystic spaces:
-lined by hyperplastic epithelium
-secondary pulmonary hypertension vascular changes
idiopathic pulmonary fibrosis (IPF) - diagnostic criteria
- chronic, progressive fibrotic usual interstitial pneumonia
- limited to the lung
- occurring primarily in older (>50) adults (male)
- chronic exertional dyspnea
- unknown origin
*diagnosis has substantial therapeutic/prognostic implications
*requires a multidisciplinary approach to rule out many other diseases
which pathologic changes explain the functional differences between idiopathic pulmonary fibrosis (IPF) and emphysema
*IPF: increased fibrosis
-causes rigid, dilated airspaces restricting lung expansion
*emphysema: decreased elastic fibers
-alveolar hyperexpansion due to air trapping caused by collapse of small airways upon expiration, producing obstruction
sarcoidosis - overview
*systematic disease of unknown etiology characterized by NONCASEATING GRANULOMATOUS INFLAMMATION
sarcoidosis - epidemiology
*predilection for adults younger than 40 years of age
*familial and racial clustering suggest involvement of genetic factors (incidence relatively high in Danish, Swedish, African descent)
sarcoidosis - pathogenesis
*sustained CD4+ Th1 T-cell response to unknown antigen
*local recruitment/activation of macrophages, forming NONCASEATING GRANULOMAS
*pathogenesis of pulmonary fibrosis uncertain:
-? shift from Th1 to Th2 cell cytokines
-activation of pulmonary macrophages, leading to activation of lung fibroblasts
sarcoidosis - gross morphology
*HILAR ADENOPATHY
*parenchymal scarring and honeycomb
sarcoidosis - microscopic morphology
*NON-NECROTIZING GRANULOMA:
-at sites of active disease
-discrete, compact epitheloid macrophages
-rimmed by a zone rich in CD4+ T cells
*admixed mutlinucleated giant cells:
-SCHAUMANN BODIES - laminated calcifications
-ASTEROID BODIES - stellate inclusions
*surrounded by ring of fibroblasts:
-produce collagen replacing granuloma with hyalinized scar
sarcoidosis - Schaumann bodies
*laminated calcifications
sarcoidosis - asteroid bodies
*stellate inclusions
*pathognomonic for sarcoidosis
sarcoidosis - clinical features
*may be asymptomatic (incidental discovery on routine chest films)
*gradual appearance of respiratory and constitutional symptoms: dyspnea, cough, fever, fatigue, weight loss, anorexia, night sweats
*multi-systemic: bilateral hilar lymphadenopathy and lung involvement; sometimes skin (lupus pernio, erythema nodosum) or bone marrow involvement
sarcoidosis - diagnosis
*diagnosis of exclusion
*no definitive diagnostic test
*exclude other disorders with similar presentations (TB must be excluded)
*establish consistent clinical and radiologic findings
hypersensitivity pneumonitis - overview
*immunologically mediated interstitial lung disease caused by intense, prolonged exposure to INHALED ORGANIC ANTIGENS
*occupational inhalation of organic dust containing antigens from thermophilic bacteria, fungi, animal proteins, or bacterial products
*examples include Farmer’s lung, Pigeon breeder’s lung
hypersensitivity pneumonitis - pathogenesis
*abnormal sensitivity or heightened reactivity to causative antigen, leads to pathology involving alveolar walls
*immunologically mediated disease:
-T CELL-MEDIATED (type IV) HYPERSENSITIVITY REACTIONS
-increased numbers of both intra-alveolar CD4+ and CD8+ T lymphocytes
-most patients have specific IgG antibodies against causative agent
hypersensitivity pneumonitis - morphology
*early phase = acute alveolar damage
*late phase = bronchiole/airway centered chronic inflammation:
-lymphocytes, plasma cells
-non-necrotizing granulomas
*chronic phase = INTERSTITIAL FIBROSIS:
-fibroblastic foci
-obliterative bronchiolitis
-honeycombing
hypersensitivity pneumonitis - clinical features
*acute attacks following inhalation of antigenic dust in sensitized patients:
-usually appear 4-6 hours after exposure and may last for 12 hours-several days
-fever, dyspnea, cough, and leukocytosis
*PFTs show an acute restrictive disorder
*imaging: MICRONODULAR INTERSTITIAL INFILTRATES
*chronic/continuous protracted exposure leads to progressive fibrosis
pneumoconioses - overview
*restrictive lung disorders due to inhalation of mineral dusts (INORGANIC AGENTS)
*causative agents include:
-coal dust
-silica
-asbestos
-berylliosis
pneumoconioses - pathogenesis
*particle phagocytosis by pulmonary alveolar macrophages:
-reaction depends on size, shape, solubility, and reactivity of particles
-chronic inflammation leads to interstitial fibroblast proliferation and collagen deposition
note - tobacco smoking exacerbates effects of all inhaled mineral dusts
Coal Worker’s Pneumoconiosis - overview
*restrictive lung disorder caused by inhalation of coal particles
*exposure = coal mining
Coal Worker’s Pneumoconiosis - pathogenesis
*coal dust phagocytosed by macrophages stimulate release of proinflammatory fibrogenic mediators
Coal Worker’s Pneumoconiosis - clinical features
*anthracosis (simple) = asymptomatic
*“Black lung” = progressive/massive fibrosis
Coal Worker’s Pneumoconiosis - morphology
*ANTRACOSIS = black carbon deposits
*coal nodules = black collagenous scars
-adjacent to respiratory bronchioles, usually upper lobes
-usually multiple
Silicosis - overview
*restrictive lung disorder caused by inhalation of silicon
*exposures: sandblasting, quarrying, mining, stone cutting, foundry work, ceramics
Silicosis - pathogenesis
*crystalline silica particles phagocytosed by macrophages releasing inflammatory mediators, e.g. IL-1
Silicosis - clinical features
*imaging: fine nodularity in upper lung/apices
*slowly progressive, leading to impairment of pulmonary function
Silicosis - morphology
*SILICOTIC NODULES = concentric whorls of collagen fibers surrounding amorphous center
-polarized birefringent silica particles
*may occur in hilar lymph nodes and pleura
*disease progression leads to honeycomb fibrosis
Silicosis - polarized silicon crystals
Asbestosis - overview
*restrictive lung disorder caused by inhalation of asbestos
*exposures: mining, milling, and fabrication of ores and materials; installation and removal of insulation
Asbestosis - pathogenesis
- fibrous crystalline hydrated silicates phagocytosed by macrophages stimulate FIBROGENIC EFFECT
- asbestos fibers generate free radicals as ONCOGENIC EFFECT (most common malignancy is mesothelioma)
Asbestosis - clinical features
*progressive dyspnea 10-20 years after exposure
*increased risk of: lung carcinoma (5x); mesothelioma (1000x)
Asbestosis - morphology
*interstitial pulmonary fibrosis
*ASBESTOS BODIES (ferruginous body) = golden brown, beaded rods with translucent center
-asbestos fibers coated with Fe
*pleural fibrosis/plaques in visceral pleura
-dense collagenous adhesions between lungs and chest wall
