Download PBL 13 Dust and Diesel Rick Allen Clinical features of restrictive

PBL 13 Dust and Diesel
Rick Allen
Clinical features of restrictive lung disease
Restrictive vs obstructive
Chronic, diffuse non-infective lung diseases are based on their effect on pulmonary
function tests;
Obstructive = ↓ airflow due to ↑ resistance
Restrictive = ↓ total lung capacity due to ↓ expansion of lung parenchyma.
Expiratory flow is either normal or proportionately reduced.
Types of restrictive disease
Chest wall disorders:
Neuromuscular diseases – poliomyelitis, Severe obesity, Pleural disease, kyphoscoliosis
Chronic diffuse interstitial and infiltrative diseases:
-
Characterised by inflam. and fibrosis of the pulmonary CT, usually the most
peripheral and delicate interstitium in the alveolar walls.
CF: dyspnoea, tachypnea, end-inspiratory crackles, eventual cyanosis (without
wheezing or evidence of obstruction)
Physiologic features: ↓ CO diffusion capacity, ↓lung volume, ↓ compliance
Complications: severe scarring and destruction (honey-comb lung), pulmonary
HTNcor pulmonaleRHF
Fibrosing diseases
Idiopathic pulmonary fibrosis (IPF) – histologic fibrosis pattern is called usual
interstitial pneumonia (UIP), needed for Dx.
Pathogenesis – repeated epithelial activation/injury  inflammatory response,
↑↑↑fibroblastic/myofibroblastic proliferation (fibroblastic foci – characteristic)  TGF-β1  ↑
fibrogenesis/collagen deposition, inhibits caveolin-1 (inhibitor of collagen/ECM deposition),
causes epithelial cell apoptosis.
Morphology – gross: fibrosis mainly in lower lobe, subpleural and along
interlobular septa. Dense fibrosis  alveolar structure destruction  honeycomb fibrosis
Clinical course: insidious onset  ↑ dyspnea on exertion and dry cough. 4070 y.o. Ltae stage = clubbing, hypoxemia, cyanosis. Mean survival <3 years. Tx. transplant
Nonspecific interstitial pneumonia (NSIP) – better Px. Than UIP. Unknown path.
Morphology – cellular pattern = mild/mod chronic inflam, lymphocytes,
patchy/diffuse. Fibrosis = diffuse/patchy interstitial fibrosis unlike UIP
Clinical course – dyspnea and cough lasting several months. 46-55 y.o.
Cryptogenic organising pneumonia –
PBL 13 Dust and Diesel
Rick Allen
Morphology – subpleural/peribronchial patchy airspace consolidation:
fibroblasts and organising CT within alveolar ducts, alveoli and bronchioles (Masson bodies).
Architecture unaffected.
Clinical course – dyspnea and cough. Can recover spontaneously. Tx w.
steroids for 6 months
CT diseases – rheumatoid arthritis, SLE, systemic sclerosis (scleroderma)
Pneumoconiosis
Lung disease resulting from inhaled airborne agents and occupational
hazards and air pollution.
Pathogenesis – Development depends on 1. The amount of agent retained in
lung and airways (dependant on concentration, duration and the effectiveness
of clearance mechanisms)(silicosis, asbestosis)
2. Size, shape and aerodynamic properties of particle (buoyancy)
3. Particle solubility and physiochemical reactivity
4. Compounding effects of other irritants (smoking)
-1-5µm diameter particles are the most dangerous as they can reach alveoli.
- interalveolar macrophages are ↑ in number to combat excessive dust levels
but can be overburdened.
-larger particles can persist in lung parenchyma for years and resist
dissolution  fibrosing collagenous pneumoconiosis (silicosis)
-smaller particles can enter lymphatics and blood  systemic response or
autoimmunity.
Eg. Coal workers pneumoconiosis: Usually benign. carbon  progressive
massive fibrosis (PMF – very nasty)
Silicosis: Slow progression, nodular, fibrosing. Inhalation of silica (silicon
dioxide)  interact w. epithelium cells and macrophages  activation and
release of IL-1, TNF, O2 free radicals, and fibrogenesis promoters  lung
collagen accumulation (nodules in upper lung  hard collagenous scars. Can
cavitate. Associated with ↑ risk of developing TB)
Asbestosis: as above, with inflammation. Cannot digest/remove. Fibrosis
begins at resp bronchioles then includes alveoli  enlarged airspace w. thick
fibrous walls. Lower lobes, subpleural. Oncogenic effects due to free radicals
released and toxic chemicals absorbed/retained by fibre (develop distally) 
lung carcinoma and mesothelioma (pleural/peritoneal). Pleural plaques,
fibrosis and effusions may occur.
Drug induced – cytotoxic chemo drugs directly damage tissue, causing macrophage
presence and fibrosis. Radiation/radiotherapy  fibrosis.
PBL 13 Dust and Diesel
Rick Allen
Granulomatous diseases
Sarcoidosis – systemic disease, non-caseating granulomas of unknown cause 
bilateral hilar lymphadenopathy and lung involvement. Blamed on dodgy immune system,
genetics and perhaps environmental exposure. Has langhans cells and looks a lot like TB,
but no caseating necrosis!
Hypersensitivity pneumonitis – inhalation of antigens  immune over-reactiveness 
firbrosis of bronchioles. Interstital pneomonitis, non-caseating granulomas, interstitial
fibrosishoneycombingobliterative bronchiolitis
Pulmonary eosinophilia
-a variety of scenarios, some of unknown origin, resulting in an increase in
eosinophils (and sometimes lymphocytes, with the stray giant cell) within the septa of the
lung, and at times in the alveola spaces. CF as per usual, but can also get high fever and
night sweats.
Smoking related interstitial diseases
Desquamative interstitial pneumonia – smokers macrophages evident within alveoli
airspaces (↑ cytoplasm, a dusty brown). Alveoli septa are thickened with lymphocytes,
plasma cells and eosinophils, and are lined with cuboidal pneumocytes. Tx. – steroids and
stop smoking.
Respiratory bronchiolitis-associated interstitial lung disease – smoker macrophages
at resp. bronchioles, alveolar ducts and peribronchioler spaces.
Pulmonary alveolar proteinosis (PAP)
-accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces.
-Acquired: autoimmune Ab against GM-CSF  impaired surfactant clearance by
alveolar macrophages.
-Congenital: mutations in surfactant protein genes  accumulation in air space.
-homogeneous granular precipitate within alveoli  foci/confluent consolidation with minimal
inflammatory reaction. ↑size and wt. of lung. Can get abnormalities in type II pneumocytes.
-CF: dyspnoea of insidious onset, cough with gelatinous containing spuptum, febrile
illnesses, cyanosis, OR benign and resolution.
Tx. – congenital = transplant. Acquired = GM-CSF therapy and whole lung lavage.