Diffuse parenchymal lung disease Flashcards

1
Q

Definiton of interstitial lung disease

A

Affect parenchyma distal to small airways
Too much of something in the interstitial space
- increased collagen, matrix proteins
- increased chronic inflammatory cells
- granulomas

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2
Q

Common interstitial lung diseases

A
Usual interstitial pneumonia (UIP) - NOT INFECTIOUS ( = idiopathic pulmonary fibrosis, IPF)
Sarcoidosis
Hypersensitivity pneumonitis (HP) - NOT INFECTIOUS
Pneumoconioses such as asbestosis
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3
Q

Clinical features of interstitial lung diseases

A

SOB
dry cough
systemic symptoms (fever, weight loss) - sometimes
clubbing with severe disease
“velcro rales” heard on inspiration
interstitial markings on plain film
restrictive pulmonary function abnormality

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4
Q

Conditions associated with UIP

A

IPF (most common)
UIP associated with collagen vascular disease (lupus, RA)
Drug-induced UIP
Familial UIP
Pneumoconioses, mainly asbestosis (not exact mimics)

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5
Q

Collagen vascular diseases associated with UIP

A
Scleroderma (high freq)
Rheumatoid arthritis (common)
Lupus erythematosus (uncommon)
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6
Q

Drugs associated with UIP

A

Most chemotherapeutic agents
Nitrofurantoin (also associated with other types of interstitial disease)
Amiodarone (as above)

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7
Q

Clinical features of UIP

A

Disease of middle-age and elderly
Typically presents with insidious onset of SOB
SOB increases over a period of months - yrs
Velcro rales on inspiration
Clubbing in ~50% cases
ANA, RF, cryoglobulins may be elevated even in those without collagen vascular disease
Restrictive functional abnormality

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8
Q

Radiographic features of UIP

A

Plain chest films: reticulonodular (“interstitial”) markers, usually more severe in lower zones
Honeycombing in advanced cases
HRCT: subpleural reticular pattern with predominantly subpleural honeycombing
Evidence of cor pulmonale may be seen in severe cases

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9
Q

Gross features of UIP

A

Predominantly lower zone fibrosis + honeycombing

Worse in periphery of lung, lobule

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10
Q

Microscopic features of UIP

A

Patchy patterns of interstitial inflammation & fibrosis mixed with normal parenchyma
Tends to be worse in periphery of lobule
Scattered fibroblast foci (small tufts of granulation tissue applied to alveolar walls)

Interstitial inflammation minimal except in honeycombed foci
Airspace macrophages minimal except in honeycombed foci
Honeycombed areas usually present by the time of biopsy
Temporal and morphologic heterogeneity

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11
Q

Morphogenesis of granulation tissue in UIP

A
  • repairative pattern of proliferative fibroblasts, often acocmpanied by capillary channels & chronic inflammatory cells
  • most organs: granulation tissue undergoes organization, gradually transformed into dense collagen

Focal epithelial injury –> local fibrin deposition, overgrowth of fibroblasts from interstitium to organize the fibrin (“fibroblast foci”) into granulation tissue

  • fibrinolytic mechanism impaired in UIP
  • overproduction of plasminogen activator inhibitor leads to lack of plasminogen & persisting fibrin

Epithelium grows over to incorporate the new granulation tissue into interstitium
Granulation tissue foci (fibroblast foci) –> interstitial fibrous tissue
Alveolar collapse with organization and eventual fibrosis –> loss of alveoli
End as old scar tissue with reorganization of parenchyma

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12
Q

UIP - granulation tissue response to steroids

A

Normal granulation tissue very sensitive to steroids (scar does not form, undergoes apoptosis)

Granulation tissue of UIP are not sensitive to steroids at all

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13
Q

Causes of restrictive lung disease

A

Interstitial lung disease
Densely fibrotic pleura (fibrothorax)
Chest wall muscle weakness
Chest wall deformity/obesity

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14
Q

Findings of restrictive lung disease

A
FVC, FEV1 small
TLC small
FEV1/FVC preserved or increased
compliance decrease
typically diffusing capacity decreased
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15
Q

Unproven hypotheses - pathogenesis of UIP

A

Triggering injury: environmental agents (smoke, metal/wood dust), viral infections (Hep C, EBV

Immunologic factors: ongoing immunologic rxn, autoantibiodies against alveolar epithelium, TH2 lymphocytes –> IL-4, IL-5 (IL-4 stimulates fibroblast proliferation), Absence of IFNgamma (inhibitor of collagen synthesis)

Cytokines: increased levels of profibrotic cytokines:
TGFbeta, TGFalpha, PDGF, IGF, endothelin-1

Fibroblast abnormalities: increased motility, increased rate of proliferation, anchorage independent growth, resistance to apoptosis, Hypermethylation of promoter of Thy-1 (makes fibroblasts insensitive to TGFbeta and decrease matrix production)

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16
Q

Complications of UIP

A

Acute exacerbation (UIP + superimposed ARDS)
Carcinoma (10x risk)
Pulmonary HTN/cor pulmonale
Respiratory failure

17
Q

Prognosis of UIP

A
Progressive
Mean survival ~3 yrs
Not responsive to steroids
Not responsive to cyclophosphamide
Lung transplant for younger patients