W4 - Pathology of Restrictive Lung Diseases Flashcards
The interstitium of the lung is comprised of connective tissue space around what 3 things?
Airways
Vessels
Basement membranes of alveolar walls
In normal alveolar walls, what 2 things are in direct contact with each other?
Alveolar epithelial (pneumocyte)
Interstitial capillary endothelial cell basement membranes
Histologically, how do healthy alveoli vs alveoli in restrictive lung disease appear? What’s the physiological relevance of this difference?
In healthy tissue, alveolar walls are 2 cells thick.
In restrictive lung disease, they are thickened by interstitial infiltrate
The thickening means gas exchange is much more difficult
What does FEV1, FVC and the ratio look like in restrictive lung disease?
FEV1 reduced
FVC reduced
FEV1/FVC ratio normal
How does restrictive lung disease affect compliance and why?
Reduced lung compliance as fibrous material prevents lungs stretching
Reduced gas transfer from restrictive lung disease is an abnormality of what?
Diffusion
Describe ventilation/perfusion balance in restrictive lung disease
Imbalance when small airways are affected by pathology
There’s more than 100 restrictive lung diseases, so it’s tricky to generalise. But what 4 symptoms are typical of restrictive lung disease?
Incidentally discovered on CXR or CT (asymptomatic)
Dyspnoea, initially SOB on exertion, then at rest as disease progresses
Type 1 Resp Failure
Heart failure, caused by cor pulmonale
An acute response to interstitial lung injury is called what?
Diffuse Alveolar Damage (DAD)
Name 3 types of chronic responses to interstitial lung disease
Usual Interstitial Pneumonitis (UIP)
Granulomatous Responses
Other Patterns
Chronic responses to interstitial lung disease lead to what?
Fibrosis or end-stage honeycomb lung
Define the natural history of restrictive lung disease generally, IPF and sarcoidosis
Generally variable
IPF - 3-6 year survival
Sarcoidosis - relatively benign self-limiting course. 20% develop pulmonary fibrosis
Name 3 examples of occupational lung diseases
Coal Worker’s pneumoconiosis
Silicosis
Asbestosis
Name 2 granulomatous diseases of restrictive lung disease
Sarcoidosis
Hypersensitivity pnemonitis
Give 3 examples of types of hypersensitivity pneumonitis
Farmer’s Lung
Bird Fancier’s Lung
Bark Stripper’s Lung
Give an example of idiopathic pulmonary fibrosis
Usual Interstitial pneumonia
Name 8 causes of DADS
Major trauma
Chemical injury/toxic inhalation
Circulatory shock, cardiac failure, blood loss
Drugs
Infection inc viruses
Autoimmune disease
Radiation
Idiopathic
What is DADS?
Diffuse Alveolar Damage Syndrome - acute inflammatory response in lung interstitium
Name 6 histological features of DADS
Protein rich oedema
Fibrin
Hyaline membranes
Denuded basement membranes
Epithelial or fibroblast proliferation
Scarring in interstitium and airspaces (fatal)
What 2 things peak in the exudative stage of DADS, then which 2 things rise in the proliferative stage?
Exudative - oedema then hyaline membranes
Proliferative - interstitial inflammation and interstitial fibrosis
What is sarcoidosis in 3 words? Where is it more common? Who does it mainly affect in terms of age and gender?
Multisystem granulomatous disorder
More common in temporate climates
Mainly young adults, F>M
Name 4 histopathological features of sarcoidosis
Epithelioid and giant cell granulomas
Unlikely to have necrosis
Little lymphoid infiltrate
Variable associated fibrosis
In what 3 ways does sarcoidosis present?
Young adult with acute arthralgia, erythema nodosum or bilateral hilar lymphadenopathy
Asymptomatic with incidental abnormal CXR/CT
SOB, cough, abnormal CXR
In what 4 ways is sarcoidosis diagnosed?
Clinical findings
Imaging findings
Serum Ca++ and ACE
Biopsy or EBUS cytology
How is sarcoidosis treated?
Corticosteroids
How do you distinguish between sarcoidosis and hypersensitivity pneumonitis in histology?
Sarcoidosis - distinct granulomas
HP - thickening of alveolar walls and softer, more diffuse granulomas
Define hypersensitivity pneumonitis
Granulomatous condition from hypersensitivity reaction to exogenous inhaled materials
Name 5 antigens that can lead to HP
Thermophilic actinomycetes (micropolyspora faeni, thermoactinomyces vulgaris)
Bird/animal proteins
Fungi (aspergillus)
Chemicals
Other
In what 8 ways does HP present if acute?
Fever, dry cough, myalgia, chills 4-9 hrs after Ag exposure, crackles, tachyopnoea, wheeze, precipitating antibody
In what 6 ways does HP present if chronic?
Insidious
Malaise
SOB
Cough
Low grade illness
Crackles and some wheeze
Name 6 histopathology features of HP
- Immune complex mediated combined Type III and IV Hypersensitivity reaction
- Soft centriacinar epithelioid granulomata
- Interstitaial pneumonitis
- Foamy histiocytes
- Bronchiolitis obliterans
Upper zone disease
Name 3 types of HP
Farmer’s Lung
Bird Fancier’s Lung
Bark Stripper’s Lung
What 2 other diseases may UIP present in?
Scleroderma
Rheumatoid disease
What 5 things may cause UIP?
Connective tissue disease
Drug reaction
Post infection
Industrial exposure (asbestos)
Other
What age and sex is UIP more prevalent in?
> 50, M>F
In what 5 ways does UIP present?
Dyspnoea
Cough
Basal crackles
Cyanosis
Clubbing
What 4 things does CXR of UIP show?
Basal/posterior
Diffuse infiltrates
Cysts
“ground glass”
Name 5 histopathology features of UIP
- Patchy interstitial chronic inflammation
- Type II pneumocyte hyperplasia
- Smooth muscle and vascular proliferation
- Evidence of old and recent injury (temporal heterogeneity or spatial heterogeneity)
- Proliferating fibroblastic foci
What does UIP stand for?
Usual Interstitial Pneumonitis
What 4 treatments can be used for UIP and what is their effectiveness? What is the prognosis for UIP?
Steroids or anti-inflammatories (don’t work very well)
Anti-angiogenic agents (minor improvement)
Transpulmonary transplantation
5 year survival
What is the endstage of restrictive lung diseases? What causes it and what do the lungs look like?
Endstage lung fibrosis/honeycomb lung
Here, progressive fibrosis damages more and more of the lungs. The lungs try to repair themselves but fail, leading to shrunken lung with non-smooth surface.
