Restrictive (5) - Gomez Flashcards
Chronic Diffuse Interstitial (Infiltrative, Restrictive) Lung Diseases (in general)
Confusing, heterogenous group of diseases
Infiltrative X-ray changes
X-ray reticulonodular or ground glass
Most involve interstitium and alveolar walls (no wheezing) but others are intraalveolar disease
Many of unknown etiology
Restrictive symptoms: decreased TLC & RV
Dyspnea, tachypnea, cyanosis, end-inspiratory crackles
End-stage/Honeycomb lung
Can lead to pulmonary hypertension and cor pulmonale
Idiopathic Pulmonary Fibrosis (IPF) - other names, description
= Usual Interstitial Pneumonia (UIP)
Also, called “Cryptogenic Fibrosing Alveolitis”
Pathogenesis unknown
Repeated injury to alveolar wall (“alveolitis”)
Lesions of variable age/progression
Type I pneumocyte death, type II hyperplasia
Inflammation with TH2 lymphocytes, cytokines, macrophages, fibroblast/myofibroblast proliferation (TGF-β1 driven), collagen deposition
Environmental factors
Smoking #1
Work related exposures
Reflux esophagitis
Genetic factors (TERT and TERC telomerase genes)
Idiopathic Pulmonary Fibrosis- Clinical, pathology and treatment
Clinical
Insidious, unpredictable disease in middle aged (>50)
Dyspnea, dry cough, hypoxemia with cyanosis, digital clubbing*
Median survival 3 years***
Pathology
Repeated cycles of alveolitis**
Healing/scarring leads to patchy interstitial fibrosis
Predominently subpleural/interlobar and lower lobe
End stage: “honeycomb lung” **
Treatment Lung transplant (does not respond well to anti-inflammatory agents)
Nonspecific Interstitial Pneumonia (NSIP)
- Patients not as sick or progressive as IPF (UIP)
- Dyspnea and cough for several months
- Middle age patients with milder symptoms (non-smoking females)
- Better prognosis than IPF
Histologically all lesions at same stage of progression with lymphocytes and some plasma cells (cellular pattern)
- Mild patchy or diffuse interstitial fibrosis
(fibrosing pattern)
- No fibroblastic foci or honeycombing
- Many eventually reclassified if it
progresses into something else
Cryptogenic Organizing Pneumonia (COP)
= Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
Unknown etiology by definition
* Organizing pneumonia in which all connective tissue is of same age and
no interstitial fibrosis, so does not progress to “honeycomb lung” (the fibrosis is happening in the alveoli)
Usually have cough and dyspnea
Cryptogenic organizing pneumonia usually requires oral steroids for > 6 months
* Organizing pneumonias can also be a reaction to known infectious and inflammatory processes
*** Masson bodies
Collagen Vascular Disorder-related Autoimmune Interstitial Lung Disease
Rheumatoid arthritis (30-40% abnormal PFT)
* Caplan syndrome - combination of rheumatoid arthritis and pneumoconiosis
Scleroderma (systemic sclerosis)
Systemic lupus erythematosus
Sjӧgren syndrome
Polymyositis/dermatomyositis
Mixed connective tissue disorder
Environmentally Related Lung Diseases
Inhalation related
Genetic predisposition to developing disease
* 1-5 micron most dangerous particle size
Amount/volume
Size, shape and buoyancy
Solubility / cytotoxicity
Concomitant irritants
** Pneumoconioses originally limited to mineral dust inhalation but now all inclusive of pretty much anything you breath at work
(coal dust, silica, asbestos, beryllium, moldy hay, bird droppings, cotton, flax, hemp, etc.)
Bagassosis
from Bagasse- manufacturing wallboard, paper, RUM
Coal Worker’s Pneumoconiosis (CWP)
- Asymptomatic anthracosis
- Simple CWP (coal macules and nodules +/-centrilobular emphysema) Usually benign disease
- Complicated CWP with Progressive Massive Fibrosis (PMF)
Scars > 2 cm
less than 10 % progress to Comp. CWP with PMF
Pulmonary dysfunction
Pulmonary hypertension
Cor pulmonale
Pathogenesis poorly understood
Concomitant silica can make
disease worse
No increased risk of TB or CA
Silicosis
- “Currently, the most prevalent chronic occupational disease in the world.”
Occurs in sandblasters, demolition crews and miners
Slowly progressive taking decades to develop
(rare acute silicosis with lipoproteinaceous material in alveoli)**
Crystalline silica, esp. quartz, fibrogenic
Silica (silicon dioxide) ingested by macrophage and mФ killed
Inflammation with release of Tumor Necrosis Factor
TNF affects fibroblasts
Potentiates carcinogenesis (2X)
More susceptible to TB
Fresh cracked silica worse
look for egg shell calcification**
Asbestos Related Diseases
Pleural effusions
Pleural plaques or diffuse pleural fibrosis
Asbestosis - Fibrotic lung disease begins in lower lobes and subpleurally
Dyspnea followed by productive cough
Lung cancer (5x vs 55x with smoking)
Laryngeal carcinoma
Mesothelioma (1000x) occurs only with amphiboles
?Ovarian and colon carcinoma
Serpentine chrysotile * (more common in industry)
VS stiff brittle amphiboles (more harmful)
Disease in wives of workers
Pathogenesis: aerodynamics and interactions
with macrophages
** Asbestos (iron/ferruginous) bodies
** no asbestos bodies in the mesothelium. Pleural plaques have no asbestos bodies!
Examples of Drug-Induced Pulmonary Disease
cytotoxic drugs: bleomycin, methotrexate
amiodarone nitrofurantoin aspirin beta antagonists ACE inhibitors
Hypersensitivity Pneumonitis
= Extrinsic Allergic Alveolitis
occupational- farmer's lung environmental- bird fancier's lung medications/ iatrogenic- humidifier lung pets/ hobbies dietary
Hypersensitivity Pneumonitis
Hypersensitivity reaction, unlike asthma, occurs at alveolar level
Removal of environmental agent can spare serious fibrotic lung
Fever, cough, dyspnea, leukocytosis hours after exposure
Interstitial pneumonitis & fibrosis if chronic (cyanosis)
Noncaseating granulomas (Type IV) in distal lung
Interstitial Lung DiseasesRelated To Cigarette Smoking
Desquamative interstitial pneumonia (D.I.P.)
Respiratory bronchiolitis associated interstitial lung disease (R.B.I.L.D.)
+/- Pulmonary Langerhans cell histiocytosis (Eosinophilic granuloma)
