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)
Desquamative Interstitial Pneumonia (D.I.P.)
Large collections of * smokers’ macrophages in alveoli (were thought to be desquamated epithelial cells)
Minimal fibrosis (not UIP precursor)
>50
Males = females
Dyspnea
Steroids and cessation of smoking curative
Respiratory Bronchiolitis-associated Interstitial Lung Disease (RBILD)
Common lesion in smokers
** Pigmented smokers’ macrophages in bronchioles
** Peribronchiolar fibrosis
Usually mild, may have dyspnea and cough
Patients with 30+ pack year history
Regresses with cessation of smoking
Pulmonary Langerhans Cell Histiocytosis
(Eosinophilic Granuloma)
Proliferation of dendritic cells in response to smoking
Usually polyclonal and felt to be reactive hyperplasia
Regresses with cessation of smoking
Usually distinct from other forms of malignant
eosinophilic granuloma (Histiocytosis X, etc.)
but occasionally neoplastic monoclonal with
BRAF mutation
Express CD1a, S-100, CD207 (langerin)
** Birbeck Granule **
Sarcoidosis
Systemic disease of unknown origin characterized by the formation of numerous non-caseating granulomas ***
- increased CD4 cells, IL-2 and cytokines…
Diagnosis of exclusion Can occur almost anywhere incl. CNS Pulmonary > eye > skin Bilateral pulmonary lymphadenopathy or lung disease in 90% Spleen and liver involved in about 3/4
Hilar LN only better prognosis than LN + lung infiltrates, better than lung parenchymal disease alone
** Can have anergy (don’t react) to PPD or Candida antigens
Polyclonal hypergammaglobulinemia
** Sarcoidosis goes along with asteroid bodies and Schaumann bodies ***
Angiotensin Converting Enzyme
** Elevated in sarcoidosis and leprosy
In lung produced by endothelial cells
Levels higher with active (versus inactive) sarcoidosis
Levels usually not elevated in other forms of granulomatous lung disease
Also elevated with Gaucher disease, primary biliary cirrhosis and amyloidosis
Pulmonary Alveolar Proteinosis
Uncommon, cough and sputum with gelatinous chunks
Bilateral, patchy distribution by X-ray
Distinctive histological picture “accumulation of acellular * surfactant in the intra-alveolar and bronchiolar spaces”
Three classes
*** Autoimmune [Acquired] (90%), 20-50 yr., variable course
Ab to GM-CSF (defective phagocytosis of surfactant)
Recurs after transplantation
- Secondary, rare, many lung disorders, incl. acute silicosis, immunodeficiency synd., malignancy, blood disorders
- Hereditary [Congenital] rare, genetic (multiple genes identified involved in GM-CSF signaling), fatal**
Rx
Pulmonary lavage and GM-CSF therapy in autoimmune
Transplant in congenital
Pulmonary Eosinophilia
Acute eosinophilic pneumonia with respiratory failure (cause unknown)
Simple pulmonary eosinophilia (eosinophilia of unknown etiology)
Secondary eosinophilia - parasitic, fungal, and bacterial infections tropical eosinophilia (microfilariae) - hypersensitivity pneumonitis allergic bronchopulmonary aspergillosis - drug allergies - asthma - vasculitis
Idiopathic * chronic eosinophilic pneumonia
*** Löeffler syndrome = transient acute pulmonary eosinophilia from any cause
Originally described with parasitic infections
