Restrictive Lung Diseases

Question 1

describe the pathogenesis of restrictive lung diseases

Answer 1

• alveolitis = damage to pneumocytes and endothelial cells
• leads to leukocytes releasing cytokines which mediate and stimulate interstitial fibrosis
• interstitial fibrosis:
  
  • decreases lung compliance and increases elasticity

Question 2

describe general features of restrictive (interstitial) lung diseases

Answer 2

• fibrosis
• decreased lung compliance (stiff) and thus increased work to breathe → dyspnea
• damage to interstitium → V/Q mismatch → hypoxia
  
  • progression to resp. failure w/ pulm. hypertension → cor pulmonale

Question 3

describe idiopathic pulmonary fibrosis (IPF)/ usual intersitial pneumonia (UIP)

Answer 3

• unknown etiology
  
  • similar processes (asbestosis and collagen vascular disease) must be ruled out prior to diagnosing IPF
• males > females
• progressive bilateral interstitial fibrosis leading to severe hypoxia and cyanosis
• progression is relentless
  
  • mean survival < 3 years
• lung transplantation only option

Question 4

describe histological findings in IPF

Answer 4

• temporal (time) and geographic (spatial) heterogeneity
  
  • mature fibrosis and young fibroblast foci
  • accentuation beneath the pleura (subpleural) and along interlobular septa
  • areas of spared, normal lung
• honeycomb change → cystic spaces lined by T2 pneumocytes or resp. epithelium

Question 5

describe what is seen in the image

Answer 5

Question 6

describe what is seen in the image

Answer 6

Question 7

describe clinical features of IPF

Answer 7

• clinical features:
  
  • gradual onset of dry cough and dyspnea
    
    • crackles on inspiration
  • cyanosis, cor pulmonale and peripheral edema in late stages
• radiology (restrictive pattern)
  
  • increased interstitial markings
  • honeycombing

Question 8

describe nonspecific interstitial pneumonia (NSIP)

Answer 8

• histopathology:
  
  • uniform fibrosing process (chicken-wire)
  • 2 variants:
    
    • cellular variant (infiltrate of lymphocytes)
    • fibrosing variant
    • may be a mixture
  • lacks honeycomb change and fibroblast foci (unlike UIP)

Question 9

describe the main differentiating factor between IPF and NSIP

Answer 9

• IPF = mainly older people
• NSIP = mainly younger people

Question 10

describe cryptogenic organizing pneumonia

Answer 10

Question 11

contrast cryptogenic organizing pneumonia vs. organizing pneumonia

Answer 11

• cryptogenic organizing pneumonia = idiopathic
• organizing pneumonia = same thing but secondary to another disease
  
  • infectious pneumonia
  • transplantation
  • collagen vascular disease

Question 12

describe collagen vascular disease

Answer 12

Question 13

describe acute interstitial pneumonia (AIP)

Answer 13

Question 14

describe lymphoid interstitial pneumonia (LIP)

Answer 14

Question 15

describe respiratory bronchiolitis - interstitial lung disease

Answer 15

Question 16

describe desquamative interstitial pneumonia (DIP)

Answer 16

Question 17

describe what is seen in the image

Answer 17

Question 18

describe sarcoidosis

Answer 18

• idiopathic systemic disease
• non-necrotizing epithelioid granulomata in many tissues and organs
• young adults < 40 years
  
  • Danish, Swedish and AAs

Question 19

describe clinical presentation of sarcoidosis

Answer 19

• variable clinical presentation
  
  • asymptomatic
  • gradual development of resp. symptoms (SOB, dry cough, vague discomfort)
  • constitutional symptoms (fever, fatigue, weight loss, night sweats)
  • severe impairment with CNS/cardiac/ocular/cutaneous involvement
    
    • 90% show lung involvement
  • may be associated with hypercalcemia (activation of vit. D by epithelioid cells)
  • elevated serum ACE
• typical bilateral hilar lymphadenopathy +/- parenchymal infiltrates on CXR

Question 20

describe the pathogenesis of sarcoidosis

Answer 20

• cell-mediated (type IV) hypersensitivity reaction to unidentified antigen
• CD4+ helper T cell driven process
  
  • intra-alveolar and interstitial accumulation of CD4 TH1 cells → secrete cytokines (INF-gamma and IL-2)
  • peripheral depletion
    
    • anergy to skin tests with Candida antigen/PPD
  • polyclonal hypergammaglobulinemia
• may lead to end-stage lung

Question 21

describe the histopathology in sarcoidosis

Answer 21

• non-necrotizing epithelioid granulomata
  
  • over time, collagen replaces the granuloma yielding a hyalinized scar
• 5-15% progress to diffuse interstitial fibrosis and honeycomb lung
• Shaumann bodies: laminated concretions of calcium and protein
• Asteroid bodies: stellate inclusion in giant cells

Question 22

Answer 22

Question 23

describe the manifestation of sarcoidosis in other organs

Answer 23

Question 24

describe the pathogenesis of hypersensitivity pneumonia (HP)/extrinsic allergic alveolitis (EAA)

Answer 24

• pathogenesis:
  
  • immunologically mediated response to an extrinsic antigen
  • type III hypersensitivity rxn
    
    • first exposure = IgG antibodies in serum
    • secondary exposure = antibodies combine with inhaled antigens to form immune complexes → inflammatory response in lung (interstitial)
  • chronic exposure = granuloma formation (type 4 hypersensitivity)

Question 25

describe the histopathology in hypersensitivity pneumonia (HP)/extrinsic allergic alveolitis (EAA)

Answer 25

• airway centered process
• chronic inflammatory infiltrate
• organizing pneumonia
• poorly formed non-necrotizing granulomata with giant cells