L17 Non-neoplastic Lung disease

• BSc


  Bachelor of Science
• MD(pathology)


  Doctor of Medicine in Pathology
• Content created by Dr Braeden Donaldson- updated by Dr Satya Amirapu
• By the end of this lecture, you should be able to:

  1. Explain the aetiology and pathogenesis in the development of asthma, and the triggering of an asthmatic attack

  2. Compare and contrast chronic bronchitis and emphysema as the primary presentations of chronic obstructive pulmonary disease

  3. Name examples of restrictive lung diseases, and recognise how these differ from obstructive lung diseases
• Lecture Outline


  • 1. Asthma
  • 2. Chronic Bronchitis
  • 3. Emphysema
  • 4. Restrictive Lung Diseases (Sarcoidosis and Asbestosis)
• Asthma


  A common (10% of children, 5% of adults) cause of reversible airway obstruction

  
• Asthma Presentation


  • Wheeze
  • Breathlessness
• Asthma Triggers


  • Allergens
  • Infection
  • Cold
  • Exertion
  • Drug-induced
  • Occupational
• Aetiology of Asthma


  • Environmental Factors
  • Genetic Factors
• Development of Atopic Asthma

  1. Allergen exposure stimulates activation of TH2 cells

  2. TH2 cells stimulate B cells to produce IgE (IL-4), and recruit eosinophils (IL-5)

  3. IgE binds to the surface of Mast cells, ready to respond to the next allergen exposure

  
• Triggering Asthma (Immediate Phase)


  Allergen re-exposure triggers: IgE-mediated mast cell degranulation, Vasodilation, increased vascular permeability, oedema, Activation of eosinophils, Vagal nerve-induced bronchospasms

  
• Triggering Asthma (Late Phase)

  1. Release of IL-5 from mast cells and TH2 cells induces infiltration of the tissues with eosinophils

  2. Repeated triggering and damage results in remodelling of the airways

  3. Eosinophils secrete factors (e.g. major basic protein, eosinophil cationic protein) that damage the tissue, particularly the epithelium

  
• Normal Mucosa


  • Goblet cell hyperplasia
  • Excessive mucus secretion
  • Chronic inflammation
  • Smooth muscle hypertrophy (and hyperplasia)
  • Mucous gland hyperplasia
  • Thickened basement membrane

  
• Obstruction in Asthma


  Obstruction is due to a combination of mucus hypersecretion and bronchoconstriction

  
• Alternative Types of Asthma

  • Non-Atopic Asthma
  • Drug-Induced Asthma
  • Occupational Asthma
• Chronic Obstructive Pulmonary Disease (COPD)

  Chronic Bronchitis vs. Emphysema

  
• Clinical Presentation of COPD

  • "Blue bloaters"
  • "Pink puffers"
• Pathogenesis of Chronic Bronchitis

  1. Aetiology: Smoking, inhaled chemical irritants, pollutants, infections, genetics? (e.g. family history of COPD)

  2. Chronic inflammation of the bronchial epithelium

  3. Goblet cell and mucous gland hyperplasia (mucous hypersecretion); smooth muscle hypertrophy (bronchospasms)

  4. Mucous plugging and bronchoconstriction

  
• Chronic Bronchitis Mucosa


  • Goblet cell hyperplasia
  • Smooth muscle hypertrophy (and hyperplasia)
  • Mucous gland hyperplasia AND serous gland atrophy
  • Mucosal changes resemble asthma, but without the Type I hypersensitivity

  
• Pathogenesis of Emphysema


  1. Repeated Infection / Inflammation

  2. Chronic Bronchitis

  3. Loss of elastic recoil, collapse of small airways

  4. Obstruction

  
• Patterns of Emphysema


  • Centriacinar
  • Panacinar
• Lung Hyperinflation


  • Flattened diaphragm
  • Apex above clavicle
  • Horizontal rib orientation
  • Decreased lung markings
  • Diminution of heart shadow
• Bullous Emphysema


  • Formation of subpleural bullae in advanced disease
• Restrictive Lung Diseases (examples)

  • Granulomatous: Sarcoidosis, Hypersensitivity pneumonitis
  • Non-granulomatous: Idiopathic pulmonary fibrosis (IPF), Asbestosis

  
• Sarcoidosis


  • Systemic granulomatous disease characterised as a disease of disordered immune regulation
  • Involves the formation of non-caseating granulomas, indicative of a cell-mediate response to an unknown antigen (autoimmune?)
  • Histological features include Langhans giant cells, Schaumann bodies, and Asteroid bodies

  
• Asbestosis


  • Caused by inhalation of asbestos particles
  • Radiological features include ivory white pleural plaques
  • Histological features include asbestos (ferruginous) bodies
• Asbestosis can cause a unique type of pleural lung cancer; mesothelioma