Pathology of restrictive lung disease Flashcards
What is the interstitium of the lung?
It is the connective tissue space around the airways and vessels and the space between the basement membranes of the alveolar walls.
How do most of the alveolar epithelial (pneumocyte) & interstitial capillary endothelial cell basement membranes interact in the normal alveolar wall?
Most of them are in direct contact
What are implications of diffuse interstitial lung disease?
- Reduced lung compliance: stiff lungs.
- Low FEV1 & low FVC but FEV1/FVC ratio is normal.
- Reduced gas transfer (Tco or Kco): diffusion abnormality.
- Ventilation/Perfusion imbalance: when small airways affected by pathology.
Presentation of diffuse lung disease
- Discovery of abnormal chest X-ray
- Dyspnoea: shortness of breath on exertion, shortness of breath at rest.
- Respiratory failure: Type 1.
- Heart failure
What 2 main responses can occur from parenchymal (interstitial) lung injury?
Acute response and Chronic response
What other responses can a chronic response lead to?
- Usual interstitial pneumonitis UIP
- Granulomatous responses
- Other patterns
All of these result in fibrosis or end-stage honeycomb lung.
What causes is diffuse alveolar damage associated with?
- Major trauma
- Chemical injury/ toxic inhalation
- Circulatory shock
- Drugs
- Infection
- Auto (immune) disease
- Radiation
Histological features of DADS (diffuse alveolar damage)
- Protein rich oedema
- Fibrin
- Hyaline membranes
- ## Denuded basement membranes
What is Sarcoidosis?
A multisystem granulomatous disorder of unknown aetiology.
Histopathology of sarcoidosis
- Epithelioid and giant cell granulomas
- Necrosis/caseation very unusual
- Little lymphoid infiltrate
- Variable associated fibrosis
Who does sarcoidosis normally affect?
Commonly affects young adults, F>M
Which organs are mainly involved in sarcoidosis?
Lymph nodes - Almost 100% Lungs - >90% Spleen - 75% Liver - 70% Skin, eyes, skeletal muscle - 50% Bone marrow - 20% Salivary glands - up to 50%
Presentation of sarcoidosis in young adults
- Acute arthralgia, joint pain
- Erythema nodosum, swollen fat under skin
- Bilateral hilar lymphadenopathy, enlargement of lymph nodes of pulmonary hilar.
What would you use to treat sarcoidosis?
Corticosteroids
What would you use to diagnose sarcoidosis?
- Clinical findings
- Imaging findings
- Serum Ca++ and ACE
- Biopsy
What are the antigens for Hypersensitivity Pneumonitis?
- Thermophilic actinomycetes: micropolyspora faeni, Thermoactinomyces vulgaris.
- Bird/animal proteins: faeces, bloom
- Fungi: Aspergillus spp
- Chemicals
- Others
What is the acute presentation of hypersensitivity pneumonitis?
- Fever, dry cough, myalgia
- Chills 4-9 hours after Ag exposure
- Crackles, tachyopnoea, wheeze
- Precipitating antibody
What is the chronic presentation of hypersensitivity pneumonitis?
- Insidious
- Malaise, SOB, cough
- Low grade illness
- Crackle and some wheeze
Histopathology of Hypersensitivity Pneumonitis
- Immune complex mediated combines type III and type IV hypersensitivity combined.
- Soft centriacinar epithelioid granulomata
- Foamy histiocytes
- Bronchiolitis obliterans
- Upper zone disease
How is Usual Interstitial Pneumonitis (UIP) usually caused?
- Connective tissue diseases: esp scleroderma and rheumatoid disease.
- Drug reaction
- Post infection
- Industrial exposure: asbestos
Most are cryptogenic or idiopathic!! - Idiopathic Pulmonary Fibrosis (IPF) or Cryptogenic Fibrosing Alveolitis (CFA)
Histopathology of UIP
- Patchy interstitial chronic inflammation
- Type II pneumocyte hyperplasia
- Smooth muscle and vascular proliferation
- Proliferating fibroblastic foci
Clinical features of idiopathic pulmonary fibrosis (this is a UIP)
- Elderly >50, M>F
- Clinical show: dyspnoea, cough, basal crackles, cyanosis, clubbing.
- CXR: basal/posterior, diffuse infiltrates, cysts
- Restrictive PFT & reduced gas transfer
- Poor prognosis: some fulminant, some steroid responsive.
What parts of the lung are involved in UIP?
- Basal and posterior fibrosis with honeycombing.
- This case is complicated by a peripheral adenocarcinoma.
What is normal PaO2 and PaCO2 for pulmonary gas exchange?
PaO2 10.5-13.5 kPa
PaCO2 4.8-6.0 kPa
How does PaO2 and PaCO2 change in type I respiratory failure?
PaO2 <8 kPa (PaCO2 normal or low)
How does PaO2 and PaCO2 change in type II respiratory failure?
PaCO2 >6.5 kPa (PaO2 usually low)
What are the 4 abnormal states associated with hypoxaemia?
- Alveolar hypoventilation
- Shunt
- Ventilation/Perfusion imbalance (V/Q)
- Diffusion impairment
What occurs during alveolar hypoventilation?
- Hypoventilation increases PACO2, and thus increases PaCO2
- Increase in PACO2 decreases PAO2, which causes PaO2 to fall
- Fall in PaO2 due to hypoventilation is corrected by raising FIO2.
FIO2 = the Fraction of Inspired air which is Oxygen
What occurs during ventilation/perfusion imbalance?
- Normal V/Q is 0.8
- LOW V/Q is COMMONEST cause of hypoxaemia encountered clinically.
- LOW V/Q in some alveoli arises due to local alveolar hypoventilation due to some focal disease.
Hypoxaemia due to low V/Q responds well to even small increases in FIO2.
Features of diffusion impairment ?
- Diseases impairing gas diffusion usually do NOT change CO2 levels
- Diffusion impairment means it takes LONGER for blood and alveolar air to equilibrate, particularly for oxygen
What changes occur during diffusion impairment?
Equilibration normally takes 0.25 seconds
Capillary transit time normally 0.75 seconds
- In disease, equilibration may take close to 0.75 seconds
PaO2 maintained at rest but……
Serious falls in PaO2 may occur on exercise
Hypoxaemia may be corrected by increasing FIO2. This increases PAO2, thus increasing rate of diffusion.
