LUNG: INTERSTITIAL DISEASES
Arthur C. Aufderheide, M.D.
Med 6728. Respiratory Medicine
INTERSTITIAL DISEASES: TYPES
Pneumoconioses (asbestos, silica, coal dust, beryllium)
Other: sarcoidosis, PAP (pulmonary alveolar proteinosis), DIP (desquamative interstitial pneumonitis)
Idiopathic
ASBESTOSIS: WORLD PRODUCTION
1870 — 50 tons
1970 — 4,000,000 tons
2008 — Close to none
LUNG: ASBESTOSIS, FIBERS
• Serpentine: chrysotile (white) asbestos
♦ Long, thin, curly (most common)
♦ Amphibole:
♦ Crocidolite (blue) asbestos
♦ Straight, rigid (most carcinogenic)
♦ Amosite (brown) asbestos
♦ Anthophylite
♦ Tremolite
ASBESTOSIS: TOXIC MECHANISMS
Macrophages phagocytose dust; dust kills cell, releasing fibrogenic factor, insulin-like growth factor, platelet-derived growth factor, et al. fibrosis
Alveolar pneumocytes slough “ulcer” Dust interstitium through “ulcer” Macrophages “seal” ulcer; pneumocytes cover them,
sealing them into interstitium In interstitium, dust:
stimulates fibrosis travels to nodes producing fibrosis
ASBESTOSIS: PATHOLOGY
Gross: diffuse; lower lobes > upper Micro:
Alveoli: macrophages Interstitium: edema fibrosis Ferruginous bodies
Macrophages product Fiber core Protein & hemosiderin coat (react positively with
iron stains) No. / gm lung = exposure index
ASBESTOSIS: PATHOLOGY (PLEURA)
Diffuse thickening
Plaques
Parietal pleura
Discrete
Benign
Lower chest
Effusion: often bloody
ASBESTOSIS: COMPLICATIONS
Latent period (exposure to disease) = 15-30 years
Pulmonary insufficiency
Progressive massive fibrosis (rare)
Cor pulmonale
Bronchogenic carcinoma
Mesothelioma
ASBESTOSIS: BRONCHOGENIC CARCINOMA
Usually peripheral adenocarcinoma, but any histologic type
can occur
Risk: no smoke 5x (“frustrated macrophage” produces
cytokines, growth factors); smoking increases neoplasia 50x
About 14% get cancer; probability related to degree of
pulmonary fibrosis
Latent period: mean = 17 years
Crocidolite worst. Chrysotile least.
ASBESTOSIS: MESOTHELIOMA (1)
Malignant mesothelioma:
Much less common than bronchus carcinoma
80+% = asbestos history
Dose-dependent
Not related to smoking
Mostly pleural; some peritoneal
ASBESTOSIS: MESOTHELIOMA (2)
Malignant mesothelioma: (Cont.)
No ferruginous bodies in them
Latent period 30 years
Die < 1 year after diagnosis
Histology:
Epithelial & spindle forms
Resemble metastatic adenocarcinoma
Mesothelioma = PAS (+), Leu-1 neg, CEA (neg),
keratin (+), procollagen type 1 (+), GLUT1
LUNG: SILICOSIS, GENERAL
Exposure: miners, sand-blasters, ceramicists, glassmakers &
granite workers
Ingredient: silica (SiO2)
Crystal form:
Si
Crystal surface exposure: hydration silicic acid necrosis &
fibrosis?
Or: activated macrophages fibroblast growth factor fibrosis?
SILICOSIS: PATHOLOGY
Pleura: adhesions Fibrosis (macrophages release fibrogenic cytokines & other
mediators that fibrosis): Nodular, both grossly & on x-ray (peribronchial,
periarterial, nodes) Black pigment at nodules periphery Nodule confluence producing massive fibrosis
Tuberculosis in past: 2/3 (+); even today = 10-15% Polarized light: silicate refractile
Small but distinct predisposition to bronchogenic carcinoma (controversial)
LUNG: ANTHRACOSIS
Black-pigmented lung
Without fibrosis or other damage
COAL-WORKER’S PNEUMOCONIOSIS: GENERAL
Frequency varies with geography and job
Lung injury due to silica in coal dust in some but not all
2% of dust in lung = quartz
COAL-WORKER’S PNEUMOCONIOSIS: PATHOLOGY (1)
Simple (dust reticulation) pneumoconiosis
X-ray: streaks, periphery to hilum
Peribronchial nodules produce traction leading to
centriacinar emphysema
Nodular lesions:
Exaggerated degree of dust reticulation form
COAL-WORKER’S PNEUMOCONIOSIS: PATHOLOGY (2)
Progressive massive fibrosis (PMF): only 10% develop this form Massive lung fibrosis Cause:
exposure degree? host sensitivity ? tuberculosis ?
Upper > lower lobe
Tuberculosis: increases but not as much in silicosis
Carcinoma: no
HEMATITE-MINER LUNG (SILICO-SIDEROSIS)
Mixed hematite (iron oxide) and silica-containing dust.
Hematite partially suppresses fibrosis.
Early: iron-containing alveolar macrophages.
Late: patchy pulmonary interstitial pneumonitis; also
fibrosis in minority.
Gross: Lung is red (hematite) and occasionally fibrotic.
SARCOID
Idiopathic (immune disorders) Distribution in many body organs
In lung: peripheral central Clinical: 0 (1/3) to moderate pulmonary symptoms
(dyspnea, cough) Pathology: noncaseating granulomas in lung, skin
(erythema nodosum on legs), eyes (iritis), liver Diagnosis: biopsy Treatment: none; steroid Outcome: 15-20% some residual lung fibrosis; few severe
SARCOID
Idiopathic (immune disorders) Distribution in many body organs
In lung: peripheral central Clinical: 0 (1/3) to moderate pulmonary symptoms
(dyspnea, cough) Pathology: noncaseating granulomas in lung, skin
(erythema nodosum on legs), eyes (iritis), liver Diagnosis: biopsy Treatment: none; steroid Outcome: 15-20% some residual lung fibrosis; few severe
BERYLLIOSIS (1)
Exposure: formerly: fluorescent light mfg; now: metal alloys
Frequency: 1-2% of exposed (host variation)
Clinical:
Acute: adult respiratory distress syndrome (ARDS)
Chronic:
immune response after latent interval
persons with HLA-DPBI glutamate 69 = susceptible Be-
specific CD4 + T-cell accumulation in lung
BERYLLIOSIS (2)
Pathology:
Sarcoid granulomas fibrosis
Giant cell inclusions (concha bodies; Schaumann bodies)
Other organs involved
Lung Ca: little (if any) increase except in very extensive
exposure
Prognosis: few (severe) cor pulmonale
HARD METAL DISEASE (COBALT)
Cobalt is hardening agent for tungsten carbide production
Produces 3 types of pulmonary disease:
Acute allergic alveolitis (sloughed type 2 pneumocyte)
Interstitial pneumonitis with fibrosis
Asthma
Steroids (especially for acute form)
TALC GRANULOMATOSIS
To increase profits, drug dealers may dilute with talc Talc is a powdered, insoluble ore Injected intravenously, lungs are showered with talc
particles Lung treats talc like foreign body Pathology: foreign body giant cell granulomas
surround talc particles
PULMONARY ALVEOLAR PROTEINOSIS (1)
Disease: failure to catabolize surfactant accumulation in alveoli
Clinical forms: congenital, secondary, acquired Sx & Signs: cough, fever. x-ray = irregular streaks &
nodules Histology:
clusters of alveoli filled with PAS-positive staining, lipid-rich surfactant with tubular and lamellar bodies
PULMONARY ALVEOLAR PROTEINOSIS (2)
Mechanism: autoimmune IgG antibody against GM-CSF (granulocyte
macrophage colony stimulating factor) this impairs GM-CSF which, in turn, inhibits surfactant
catabolism congenital: some = mutation in several surfactant genes
Dx: history, x-ray, bronchial lavage, biopsy Rx & Prognosis: repeated bronchial lavage 75% survival
@ 5 yrs
DESQUAMATIVE INTERSTITIAL PNEUMONITIS
MISNOMER! Smoking-induced
engorgement of alveoli by
macrophages.
FARMER LUNG (HYPERSENSITIVITY DISEASE or EXTENSIVE ALLERGIC ALVEOLITIS)
Exposure: moldy hay and silage Cause: spores actinomycetes hypersensitivity (not
infectious!!) Clinical:
fever dyspnea okay 3-4 weeks
FARMER LUNG (HYPERSENSITIVITY DISEASEor EXTENSIVE ALLERGIC ALVEOLITIS)
Pathology: Granulomas and giant cells in bronchioles & alveoli
fibrosis Antibodies actinomycetes in serum Many recurrent attacks lung fibrosis
Other antigens: Mushroom compost, maple bark, moldy barley, “humidifier
fever”— actinomycetes, coffee bean, pigeon-breeders, I-tryptophane—eosinophils
SILO-FILLER DISEASE
Acute, necrotizing bronchiolitis after exposure in recently filled silo
Bronchiolitis may go on to organizing pneumonia Cause:
NO2 + H2O HNO3
This nitric acid can destroy the bronchi’s lining epithelium Rx:
prevention steroids
LANGERHANS CELL HISTIOCYTOSIS
Part of Histiocytosis-X: ( Robbins p.701) Letterer-Siwe disease < 2 yrs Hand-Schüller-Christian disease (calvaria, orbit, diabetes
insipidus)- multi-system Eosinophilic granuloma
Interstitial nodular infiltrate of Langerhans cells (giant histiocyte with club-like “Birbeck” granules and antigen CD1A positive staining cell membrane), T-lymphocytes and eosinophils. 90% smoke.
GOODPASTURE SYNDROME
Antibody directed at basement membranes of lung & kidney Acute glomerulonephritis with interstitial pulmonary
necrosis & hemorrhage (hemoptysis) Cause? M:F = 6:1. Immune complexes deposit in
glomerulus & lung capillaries Dx: Serologic identification of anti-glomerular basement
membrane antibody Rx: Eliminate antibody with plasmapheresis;
immunosuppression. Treat early. Prognosis: 50+% mortality (renal failure)
CHURG-STRAUSS SYNDROME
Sx: asthma, skin lesions, sinusitis, eosinophilia some: bloody diarrhea, kidney
Path: diffuse pulmonary interstitial infiltrate with eosinophils
Cause: idiopathic. Some: leukotriene dysfunction Anti-myeloperoxidase antibodies=vasculitis
Rx:immunosuppression CysLt1 (cysteinyl leukotriene receptor type 1)
antagonist
IDIOPATHIC PULMONARY FIBROSIS (IPF) / USUAL INTERSTITIAL PNEUMONIA (UIP)
Frequency: Most common form of diffuse interstitial fibrosis
Rx:Steroids
Nonspecific pulmonary fibrosis (NSPF): more regularly distributed. Better prognosis.
Chronic interstitial inflammation and irregularly-distributed, especially subpleural fibrosis
End-stage: “honey-comb lung”
Reactive process (immunoregulation disturbance ?) Lymphocyte Infiltrates common in bone marrow,
skin, lung, stomach.
IDIOPATHIC PULMONARY FIBROSIS (IPF) / USUAL INTERSTITIAL PNEUMONIA (UIP)
Etiology: unknown. Familial: point mutation in gene for prosurfactant protein C
Symptoms: Age: >60 Shortness of breath, cyanosis, right heart failure . Caveolin normally protects against pulmonary fibrosis by
suppression of transforming growth factor B1; caveolin is depressed in pulmonary fibrosis
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