8. Restrictive lung diseases Flashcards
Definition of restrictive lung diseases
Characterized by reduced expansion of the lung parenchyma due to decrease compliance & decreased total lung capacity; restrictive defects occur in two general conditions, of which only the latter will be discussed here:
(i) chest wall disorders – neuromuscular disorders, kyphoscoliosis, pleural diseases, obesity
(ii) interstitial lung disease;
2 clinical patterns of restrictive pulmonary disease
- Acute restrictive lung disease
- Characterised by protein exudation & edema
- E.g acute respiratory distress syndrome - Chronic restrictive lung disease
- Characterised by inflammation & fibrosis
- E.g chronic interstitial lung disease, pneumoconiosis
Common End Result of Chronic Interstitial Lung Diseases
- Honeycomb lung
- Cut surface of lung resembles honeycomb - Complications
- Chronic respiratory impairment
- Pulmonary hypertension
- Right ventricular hypertrophy
- Cor pulmonale
Definition of Acute respiratory distress syndrome
Characterized by the sudden onset of significant hypoxemia & diffuse pulmonary infiltrates in the absence of cardiac failure
Causes of acute respiratory distress syndrome
- Septicaemia*
- Diffuse pulmonary infections*
- Viral, Mycoplasma, Pneumocystis, miliary tuberculosis - Severe trauma*
- Aspiration of gastric contents*
- Inhalation of toxic fumes, chemical injury
- Acute pancreatitis
- Uremia
- more than 50% of acute respiratory distress syndromes are associated with these four conditions
Morphology of acute respiratory distress syndrome
[Histology]
- Diffuse alveolar damage
- Alveolar walls line with waxy hyaline membrane, composed of fibrin rich edema fluid & necrotic epithelial cell debris
Pathological Effects & Complications of acute respiratory distress syndrome
- Acute respiratory failure
2. Interstitial fibrosis (with failure of resolution)
Definition of chronic interstitial lung disease
Heterogeneous group of disorders characterized by inflammation & fibrosis of the pulmonary connective tissue, principally the most peripheral & delicate interstitium in the alveolar walls
Types of chronic interstitial lung disease
- Idiopathic Interstitial Pneumonitis
- Systemic Connective Tissue Diseases
- Complications of Therapies
- Complication of Atypical Pneumonias
- External Allergic Alveolitis (Hypersensitivity Pneumonitis)
- Sarcoidosis
- Pneumoconiosis
How does Idiopathic Interstitial Pneumonitis results in restrictive lung disease
- Postulated to be due to repeated cycles of epithelial injury or activation by some unidentified agents
- Clinical features:
- Initially, increasing dyspnea on exertion & dry cough
- Later, hypoxemia, cyanosis & clubbing
- Mean survival of 3 years or less
- Lung transplant as only definitive treatment
How does Systemic Connective Tissue Diseases results in restrictive lung disease?
- Rheumatoid arthritis
- Pulmonary involvement occurs in 30-40% of cases
- Presents as (i) chronic pleuritis with/without effusion, (ii) diffuse interstitial pneumonitis & fibrosis (iii) intrapulmonary rheumatoid nodules, or (iv) pulmonary hypertension - Systemic lupus erythematosus
- Presents as diffuse interstitial fibrosis - Systemic sclerosis
- Presents as patchy, transient parenchymal infiltrates & occasionally severe lupus pneumonitis
How does the Complication of therapies results in restrictive lung disease?
- Drug-induced lung diseases
- Chemotherapeutic agents (e.g. bleomycin), anti-arrhythmic drug (e.g. amiodarone)
- Cause significant pneumonitis in some patients - Radiation-induce lung diseases (radiation pneumonitis)
- Results from therapeutic radiation of thoracic tumours (lung, esophageal, breast, mediastinal)
How does Complication of Atypical Pneumonias results in restrictive lung disease?
- Atypical pneumonias present as interstitial pneumonitis which principally involves inflammatory infiltration of the alveolar septum & interstitium
- With failure to fully resolve, organization of interstitial infiltration & exudation results in interstitial fibrosis
How does External Allergic Alveolitis (Hypersensitivity Pneumonitis) results in restrictive lung disease
- Involves types III & IV hypersensitivity reactions towards inhaled organic agents
- In contrast to asthma which involves the small
airways, external allergic alveolitis primarily affects
the alveoli - Specifically named syndromes include:
- Farmer’s lung (results from exposure to dusts generated from harvested humid & warm hay which permits the rapid proliferation of the spores of thermophilic actinomycetes)
- Bird fancier’s disease (provoked by proteins from serum, excreta or feathers of birds)
- Humidifier lung (caused by thermophilic bacteria in heated water reservoirs)
How does Sarcoidosis results in restrictive lung disease?
- Idiopathic systemic disease characterized by formation of non-caseating granulomas in multiple tissues & organs
- Lungs, eye, skin, lymph nodes, bone marrow, heart, kidney, central nervous system, endocrine glands etc - Pulmonary involvement results in:
- Respiratory insufficiency
- Progressive pulmonary fibrosis
- Cor pulmonale
Definition of Pneumoconiosis
Pulmonary diseases caused by the inhalation of inorganic dusts
Pathogenesis of Pneumoconiosis
- Development of a pneumoconiosis depends on:
- Amount of dust retained in lung & airways (depends on dose of inhalation & effectiveness of clearance mechanisms such as the mucociliary escalator)
- Size & shape of particles (smaller & more streamlined particles tend to reach the terminal alveoli more easily where they can settle in the alveolar linings)
- Solubility of particles (the less soluble, the more likely it is to persist in the lung parenchyma to evoke a fibrosis collagenous pneumoconiosis)
- Possible additional effects of other irritants (e.g. smoking, which paralyses the mucociliary escalator) - Lung damage occurs due to alveolar macrophage response to dust particles, producing a chronic interstitial lung disease
- Release of cytokines promoting inflammation
- Organization over time to produce fibrosis - End result is a restrictive lung disease
Types of pneumoconiosis
- Coal Workers’ Pneumoconiosis
- Silicosis
- Abestosis
Coal Workers’ Pneumoconiosis
- Due to exposure to coal dust
- Presents in a variety of ways:
- Asymptomatic anthracosis (ingestion of inhaled carbon by alveolar macrophages, which then accumulate in the connective tissue; also seen in urban dwellers & smokers)
- Simple CWP (presents with small, scattered, nodular lung lesions comprising carbon-laden macrophages, primarily located adjacent to respiratory bronchioles in the upper lobes & upper zone of lower lobes)
- CWP with progressive massive fibrosis (presents with large nodular lesions comprising dense collagen & pigment with central ischemic necrosis; progression of disease results in fibrosis) - Pathological effects & complications:
- Centrilobular emphysema (with simple CWP, due to
eventual dilation of respiratory bronchioles)
- Progression of progressive pulmonary fibrosis to increasing pulmonary dysfunction, pulmonary hypertension & eventual cor pulmonale
Silicosis
- Due to inhalation of silicon dioxide
- Individuals working in granite quarrying, stone masonry & slate mining are at risk - Presentation:
- Short exposure → alveolar exudation (acute silicosis)
- Prolonged exposure → simple nodular silicosis (typically in upper lobes) & progressive massive fibrosis as individual lesions expand & coalesce - Pathological Effects & Complications:
- Tuberculosis (postulated to be due to silica inhibition
of pulmonary macrophage ability to kill phagocytosed mycobacteria; forms silicotuberculous nodules with central caseous necrosis)
Abestosis
- Due to exposure to asbestos fibres, which occurs in two morphological forms:
- Serpentine: more common, flexible & curled structure, usually not pathogenic (as it is large & irregular in shape, making it more easily arrested in the upper airways to be swept upwards by the mucociliar escalator, decreasing the time it resides within the lung)
- Amphibole: less common, straight & stiff structure, main cause of asbestosis (as it is smaller and more streamlined, hence able to travel to periphery and accumulate within the interstitium) - At risk groups: individuals who work in mining & refining of asbestos, building industry, shipyards
- Risk & progression of disease depend on:
- Duration & intensity of asbestos exposure
- Concomitant cigarette smoking (as carcinogens are adsorbed onto surface of asbestos fibres) - Presentation:
- Progressive fibrosis of lung
- Pleural effusion & pleural thickening
- Benign fibrous plaques of pleura - Pathological effects & complications
- Carcinoma of lung (risk amplified by smoking - asbestos only = 5x; asbestos + smoking = 55x)
- Mesothelioma of pleura (risk is not amplified by smoking)
