Lung Pathology Diffuse Interstitial Restrictive Diseases

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Lung Pathology Diffuse Interstitial
(Restrictive) Diseases
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• Complications of Therapies
• 1. Drug-Induced Lung Diseases
• Bronchospasm - Aspirin, ß-Antagonists
• Interstitial fibrosis - Bleomycin by direct
  toxicity
• Pneumonitis - Amiodarone
• Hypersensitivity pneumonitis Methotrexate,
  Nitrofurantoin
• 2. Radiation-Induced Lung Diseases
• complication of therapeutic radiation of
  pulmonary or other thoracic tumors (esophageal,
  breast, mediastinal)
• Two forms
• Acute and Chronic

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Lung - Pathology
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Granulomatous diseases

• Sarcoidosis Hypersensitivity
  Pneumonitis

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• Sarcoidosis
• Systemic disease of unknown cause
• Non-caseating granulomas many organ systems
• Clinical patterns
• MC (in 90) - bilateral hilar lymphadenopathy or
  lung involvement
• Next Common - Eye and skin
• women gt men
• In United States-highest in the Southeast
• 10 times higher in African Americans than in
  whites.
• Rare among Chinese and Southeast Asians
• Diagnosis - by exclusion.
• Other diseases with Granulomas - TB or fungal
  infections and Berylliosis
• Etio -Pathogenesis
• unknown,
• evidence suggest -disordered immune response in
  genetically predisposed individuals exposed to
  certain environmental agents

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• Sarcoidosis
• Etio -Pathogenesis
• 1. Immunologic Factors.
• Important cells CD4 T cells
• In Intra-alveolar space
• accumulation of CD4 T cells (CD4CD8 ratio
  101)
• high TNF level ( marker of disease activity)
• Systemic immunologic abnormalities
• Anergy to Candida or PPD skin test antigens
• Polyclonal hypergammaglobulinemia
• 2. Genetic Factors
• Familial and racial clustering
• HLA association (A1B8)
• 3. Environmental Factors.
• Several microbes proposed but no unequivocal
  evidence
• Example mycobacterium, Propionibacterium acnes,
  and Rickettsiae

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• Sarcoidosis
• Morphology
• Classic noncaseating Granulomas (clustered
  Epithelioid cells with
• Langhan's or foreign body type giant cells)
• Central necrosis is unusual.
• With chronicity- Granulomas replaced by hyaline
  fibrous scars
• Two other microscopic features - characteristic
  but not Pathognomonic
• Schumann bodies -laminated concretions of calcium
  and proteins
• Asteroid bodies Stellate inclusions within giant
  cells
• Lungs
• ?frequency of granulomas in the bronchial sub
  mucosa
• ( high diagnostic yield of bronchoscopic
  biopsies)
• In bronchoalveolar lavage - lymphocytes
• CD4/CD8 ratio gt2.5
• CD3/CD4 ratio lt0.31

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• Sarcoidosis
• Lymph nodes involved in almost all cases (hilar
  and mediastinal )
• Spleen involved in ¾ of cases, but - enlarged
  1/5th with granulomas
• Liver contain scattered Granulomas, more in
  portal triads
• Bone phalangeal bones show small circumscribed
  Osteolytic areas
• Skin lesions subcutaneous nodules, focal,
  slightly elevated, erythematous plaques or flat
  lesions , resemble those of SLE)
• Mikulicz syndrome Bilateral parotid involvement
• (What are the other conditions?)
• Muscle involvement under diagnosed
• Muscle biopsy very useful (you see Granulomas)

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• Sarcoidosis
• Clinical (majority of cases) respiratory
  abnormalities (shortness of breath, cough, chest
  pain, hemoptysis)
• Clinical course 2/3rd of affected patients
  recover completely
• 20- permanent loss of some lung function or some
  permanent visual impairment.
• remaining 10 to 15, some die (CVS or CNS
  damage), but most -progressive pulmonary fibrosis
  and cor pulmonale
• Prognosis Best with hilar lymphadenopathy alone

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Granulomatous diseases

• Sarcoidosis
• Hypersensitivity Pneumonitis

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• Hypersensitivity Pneumonitis"allergic
  alveolitis".
• immunologically mediated, interstitial, lung
  disorders caused by intense exposure to inhaled
  organic dusts and occupational antigens
• MCC - inhalation of organic dust containing
  antigens ( spores of thermophilic bacteria, true
  fungi, animal proteins, or bacterial products)
• Syndromes
• 1. Farmer's lung - exposure to dusts generated
  from harvested humid, warm hay ( spores of
  thermophilic actinomycetes)
• 2. Pigeon breeder's lung (bird fancier's disease)
  - proteins from serum, excreta, or feathers of
  birds
• 3. Humidifier or air-conditioner lung -
  thermophilic bacteria in heated water reservoirs

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• Hypersensitivity Pneumonitis"allergic
  alveolitis".
• Morphology
• involves primarily the alveoli (unlike in asthma)
• intra-alveolar infiltrate
• Changes in bronchioles
• interstitial pneumonitis, noncaseating
  granulomas, interstitial fibrosis and
  obliterative bronchiolitis
• Rx - Best way recognize these diseases early in
  their course
• Clinical Features
• Acute and Chronic