Flashcards in Resp Path 3 - RESTRICTIVE DZ (Fibrosing Dz, Granulomatous Dz), Smoking related interstital dz, Other interstitial dz - Galbraith Deck (66):
What characterizes chronic diffuse interstitial diseases?
Inflammation and pulmonary interstitial tissue fibrosis, particularly involving the alveolar walls.
What clinical and functional changes constitute restrictive lung disease due to interstitial fibrosis?
Decreased of diffusion lung capacity, volumes, and compliance without evidence of airway obstruction.
Long term sequelae of restrictive lung disease.
Pulmonary HTN and cor pulmonale.
End stage: parenchymal destruction and scarring
What is honey-comb lung?
Indicative of end stage restrictive lung disease. Parenchymal destruction and scarring.
Histological and clinical features of chronic diffuse interstitial diseases.
What fibrosing disease is a disorder of unknown cause, but characterized by PROGRESSIVE PULMONARY INTERSTITIAL FIBROSIS?
Idiopathic Pulmonary Fibrosis
Postulated pathogenesis of Idiopathic Pulmonary Fibrosis
REPEATED CYCLES of epithelial activation/injury, causing abnormal "wound healing" resulting in EXCESSIVE FIBROBLAST PROLIFERATION (driven by TGF-B1).
Sources of injury to epithelium in Idiopathic Pulmonary Fibrosis (5)
Persistent gastric reflux
Genetic: telomerase mutations (TERT, TERC)
What three disorders have a pathologic morphologic pattern of fibrosis denoted "Unusual Interstitial Pneumonia" (UIP)?
Connective tissue disorders
Chronic hypersensitivity pneumonia
Describe UIP morphology
- SUBPLEURAL AND INTERLOBULAR septal fibrotic distribution (around alveolar edges, works inward), as well as lower lobe predominance.
- PATCHY INTERSTITIAL FIBROSIS with VARIABLE AGE
- Honeycomb fibrosis/lung = due to destruction of alveolar architecture.
- NEW FIBROBLASTIC FOCI mixed with more densely fibrotic areas
Characteristics of honeycomb fibrosis
dense fibrosis and cystic spaces lined by hyperplastic type II pneumocytes (tall cells) or bronchiolar epithelium
Fibroblastic Foci are indicative of what stage of what lesion?
EARLY lesion of idiopathic pulmonary fibrosis
Clinical course of Idiopathic Pulmonary Fibrosis.
>50yo initially presents with DOE, dry cough. Progresses to hypoxemia, cyanosis, clubbing.
Median survival of Idiopathic Pulmonary Fibrosis.
Lung transplant only definitive tx.
What develops as EITHER interstitial chronic inflammation OR interstitial fibrosis, NO heterogeneity.
Nonspecific interstitial Pneumonia
The 2 common histologic patterns seen in Nonspecific Interstitial Pneumonia (NSIP)
1. CELLULAR >> Moderate chronic interstitial inflammation.
2. FIBROSING >> Interstitial fibrosis - **more homogenous in age than UIP.**
Demographic and clinical course associated with Nonspecific interstitial Pneumonia.
- Females in 50s.
- No smoking association
- Presents with dyspnea and cough.
Loose fibrous tissue balls that fill terminal bronchioles, alveolar ducts, and alveolar spaces.
Cryptogenic Organizing Pneumonia (COP).
COP presentation and treatment/recovery.
- Present with cough/dyspnea.
- Most require steroid therapy, but can recover spontaneously.
Interstitial fibrosis in COP?
Pulmonary involvement patterns in CT diseases (i.e. SLE, RA, scleroderma)
NSIP, UIP, vascular sclerosis, organizing pneumonia, bronchiolitis.
Better prognosis with idiopathic UIP.
What is a group of non-tumor lung diseases in a setting of INHALATION exposure to mineral dusts, inorganic and organic particles, and chemical fumes?
What four factors determent particle pathogenicity in pneumoconiosis?
- Particle size (**1-5 micrometers most dangerous >> can reach terminal alveoli)
- Particle solubility
- Level and duration of exposure/effectiveness of clearance.
- Intensity of immune response (can cause fibroses)
Two types of pneumoconiosis.
1. Coal Workers' Pneumoconiosis (CWP)
Carbon dust causes...
- Anthracosis to
- CWP (w/o significant pulmonary dysfunction) to
- Complicated-CWP to
- Progressive Massive Fibrosis (PMF)
Describe anthracosis. Histo and demographic.
BLACK pigmented lesions formed by inhaled carbon that's taken up by alveolar and interstitial MACROPHAGES. Accumulate in LYMPHATICS an lymphoid tissues.
- Seen in CWP, smokers, urban dwellers.
Describe simple Coal Workers' Pneumoconiosis
- Little functional decrement
- 1-2mm COAL MACULES composed of dust-filled macrophages; slightly larger coal nodules also contain collagenous networks.
- Located primarily adjacent to RESPIRATORYBRONCHIOLES
Describe Progressive Massive Fibrosis (PMF)
(aka - complicated CWP)
- Develops in less than 10%.
Multiple anthracotic scars, which may lead to:
- Respiratory failure, pulmonary HTN, cor pulmonale
- Due to prolonged inhalation of silica crystals. Ingested by macrophages activates MACROPHAGES >> causing fibrosis and COLLAGEN deposition.
- Results in chronic, progressive nodular fibrosis in HILAR LN and APEX
Calcified hilar LN on xray, think what?
- Polarized light show BIREFRINGENT silica particles.
- See hyalinized PINK WHORLS OF COLLAGEN balls with scant inflammation, surrounded by macrophages
What part of the lung does silicosis typically start?
At what stage of silicosis is dyspnea typically present? Describe the disease's progression.
- Progressive massive fibrosis occurs and then dyspnea.
- Disease can progress after exposure ends
What two potential silicosis sequelae diseases that have increased risk.
Increased risk for TB, lung cancer
Group of fibrous hydrated silicate crystals that cause interstitial and pleural fibrosis.
What two cancers are linked with asbestos?
Lung carcinoma and malignant mesothelioma.
**especially with smoking**
Name the two forms of asbestos and their pathogenicity.
1) Amphiboles - more pathogentic, reach deep lung more readily than serpentine
2) Serpentine fibers - curved, less pathogenic, more soluble
Pathogenesis of asbestos-related lung disease. Histo and what part of lung affected first?
- Macrophages ingest particles >> activation of mediators. SEE ASBESTOS BODIES (or ferruginous) WITHIN MACROPHAGES.
- BASE affected first.
Two morphologic features of asbestos
1. Pleural plaques - well circumscribed (collagen) that don't contain asbestos bodies. Asymptomatic.
2. Asbestosis - diffuse interstitial fibrosis, indistinguishable form UIP, EXCEPT for PRESENCE OF ASBESTOS BODIES.
Clinical course of asbestos-related lung disease.
- Decades to appear. s/s first dyspnea, then productive cough.
- Can result in pleural effusion
- POOR prognosis for asbestosis and lung/pleural malignancy
Name complications of therapies that can lead to restrictive diseases.
1. Drug induced lung diseases: ASPIRIN=acute bronchospasm; AMIODARONE=pneumonitis; BLEOMYCIN=fibrosis
2. Radiation induced lung diseases - with acute radiation pneumonitis 1-6mo post-therapy >> can progress to >> chronic radiation pneumonitis (pulmonary fibrosis)
What disease is characterized by:
- noncaseating granulomas in all tissues with multinucleated giant cells.
- 90% having hilar LN or lung involvement.
- unknown cause
A dx of exclusion
Sarcoidosis, think what race/sex?
African Americans! Females.
Sarcoidosis caused by what possible disordered immune responses in genetically predisposed peoples?
- **HLA-A1 and HLA-B8 associated genotypes**
- Accumulation of CD4+ T-cells
- Increased Th1 cytokine production that causes macrophage activation and T-cell expansion
- Inc macrophage TNF production, leading ot granuloma formation.
- Polyclonal hypergammaglobulinemia
Sarcoidosis morphology in the:
- Spleen, liver
- Bone marrow
- Lungs - scattered granulomas that may for a grossly apparent reticulonodular pattern on x-ray
- LN - hilar and mediastinal regions
- Spleen, liver - HSM
- Bone marrow - often phalangeal predilection in 20% of sarcoidosis cases
- Skin - up to 50% have subcutaneous nodules or erythematous scaling plaques
- Eyes - up to 50% have iritis, iridocyclitis, or choroid retinits. Possible concurrent salivary gland involvement
What is mukilcz syndrome?
Concurrent salivary gland involvement with eye involvement in sarcodisosis
Where are grossly apparent (2cm) granulomatous nodules found in Sarcoidosis?
lungs, distributed along pulmonary lymphatics.
Constitutional and pulmonary s/s in sarcoidosis.
Variable, but most with insidious onset of respiratory difficulty (dyspnea, hemoptysis, fatigue, night sweats) or constitutional symptoms (fever, night sweat, weight loss).
While sarcoidosis may spontaneously resolve, what are possible residua?
- 20% have residual pulmonary impairment
- 10% develop pulmonary fibrosis, P-HTN, and cor pulmonale
(70% have no residua)
How is sarcoidosis dx?, explain
- DIAGNOSIS OF EXCLUSION.
- Must establish biopsy of NONCASEATING "naked" GRANULOMAS
- Rule out TB, fungal infections - anything with the same histology
What is this:
A spectrum of immunologically mediated interstitial disorders caused by inhaled dusts or antigens. Primarily affects the alveoli.
Hypersensitivity Pneumonitis, "allergic alveolitis"
Name three possible sources of antigen in Hypersensitivity Pneumonitis.
1. Farmer's Lung - actinomycete spore in hay (spore forming fungi/bacteria)
2. Pigeon breeder's lung - proteins form bird feathers or exretions
3. Air-conditioner lung or humidifier lung - thermophilic bacteria (heated water reservoirs)
In Hypersensitivity Pneumonitis, what three things does the immunologic reaction to inhaled organic antigens cause?
1) Interstitial pneumonitis (WBCs - lymphocytes, plasma cells (macrophages) in bronchioles
2) Noncaseating granulomas in bronchioles
3) Interstitial fibrosis
Clinical manifestation of Hypersensitivity Pneumonitis.
- s/s - cough, dyspnea, fever, diffuse and nodular radiographic densities.
- cessation of exposure may prevent progression
Name five different types of pulmonary eosinophilias.
All characterized by interstitial or alveolar eosinophil infiltrates.
1. Acute eosinophilic penumonia with respiratory failrue
2. Simple pulmonary eosinophilia (Loeffler syndrome)
3. Tropical eosinophilia (cause: microfilarieae)
4. Secondary eosinophilia (induced by infection)
5. Idiopathic chronic eosinophilic pneumonial
What is this?
A 30s-40s yo (M=F) presents with insidious onset of dry cough, dyspnea, and clubbing, often with EMPHYSEMA.
Desquamative Interstitial Pneumonia - SMOKING RELATED INTERSTITIAL DISEASE
Abundant DUSTY BROWN (smokers') MACROPHAGES in alveolar spaces.
- MINIMAL Fibrosis
Histology of Desquamative Interstitial Pneumonia
Tx of Desquamative Interstitial Pneumonia
steroids, stop smoking
What is this:
Peribronchiolar inflammation and mild fibrosis with bronchiolar accumulations of smokers' macrophages.
Respiratory bronchiolitis-associated interstitial lung disease - SMOKING RELATED INTERSTITIAL DISEASE
S/s and Tx for Respiratory bronchiolitis-associated interstitial lung disease
s/s - cough and dyspnea in a long term smoker
tx - smoking cessation
Accumulations of dendritic cells (Langerhans cells) into NODULES, w/ fibroblasts, macrophages, and many eosinophils
- Lesions are due to reactive processes or BRAF mutations
Pulmonary Langerhans Cell Histiocytosis
Demographic of Pulmonary Langerhans Cell Histiocytosis.
What physically happens in Pulmonary Alveolar Proteinosis?
Accumulation of surfactant in alveoli and bronchioles, secondary to diminished pulmonary macrophage activity.
People with PAP present how - clinically and histologically?
- Clinically - coughing up sputum and gelatinous material
- Histo - alveoli filled with granular pink precipitate (lipid-laden, PAS-positive Schiff)
Progression and tx for PAP
- May have progressive respiratory failure.
- Tx - whole lung lavage, GM-CSF