Lecture 11 - toxic caused respiratory disease Flashcards
What are the common etiology’s of common lung pathologies
Inhalation of toxic/noxious substances (tobacco, dust etc.)
Inhalation of infectious agents (virus, bacteria etc.)
Inhalation of allergens (pollen etc.)
What is emphysema
destruction of airspaces distal to terminal bronchioles -> irreversible enlargement
What is the most common form of emphysema
Centriacinar - respiratory bronchioles affected but distal alveoli remain normal
What is the gross morphology of centriacinar emphysema
‘Holes’ - in lung parenchyma (air spaces) - black due to carbon pigment deposition
- When tar in cigarette smoke called anthracosis
Describe the pathogenesis of emphysema
Oxidants and proteases (elastases) - released from inflammatory cells - destroy elastic tissue in airspace walls
- smoking impairs activity of naturally occurring anti-protease (alpha-1 antitrypsin)
Why does expiration obstruction occur
Loss of elastic recoil of airspaces - destruction of elastic fibres
Airways collapse during expiration
Chests become hyperinflated - air trapping - develop dyspnea
What is chronic bronchitis
Persistent cough - sputum (at least 3 months)
Initiating factor - cigarette smoke
Bronchi show mucus hypersecretion, inflammation, recurrent infections and fibrosis
Eventually become hypoxemic and cyanosed and edema from right side heart failure
Describe the pathogenesis of chronic bronchitis
Inflammatory mediators and growth factors
- Metaplasia (-> goblet cells)
- Hypertrophy & hyperplasia of mucus secreting glands
Results in mucus hypersecretion - initially protective mechanism but causes airway obstruction - predisposes to infection (perpetuates chronic bronchitis)
What is the etiology of lung cancer
Cigarette smoking main risk factor
- Heavy smoking increase risk 60x - other factors involved (risk never returns to ‘normal’ but reduces after quitting for over 10 years)
- Second hand smoking doubles risk
Describe lung cancer pathogenesis - tobacco smoke
Tobacco smoke has >70 known carcinogens
Causes mutation in DNA - accumulate over time
Induces inflammatory response - tumour growth, immune suppression
Describe adenocarcinoma
40-50% of cases (peripheral under pleura)
- forms glands - can produce mucin
- gain-of-function mutation on oncogenes EGFR and KRAS
- Least common in smokers (most common in non-smokers and women)
Describe squamous cell carcinoma
20-25% of cases (hilar/central)
- Strong association with smoking
- High frequency of loss-of-function of tumour suppressor p53 - few RB mutations
(pseudostratified becomes squamous)
Describe small cell carcinoma
15-20% of cases (hilar/central)
- Strongest association with smoking
- highly malignant - no precursor/premalignant lesions
- Mutation of p53 and BCL2 anti-apoptotic gene
- arises from neuroendocrine cells - small cells, vry little cytoplasm
What % of cases are large cell carcinoma and others
10% of cases
What is dysplasia
‘disordered growth’ - permanent change
- driven by acquisition of genetic mutations in epithelium (effect of carcinogens)
