patoloji-ders-notlari
Title
Serdar Balcı
Chronic Obstructive Pulmonary Diseases Emphysema and Chronic Bronchitis
Serdar BALCI, MD
Obstructive Lung Diseases
Airway disease
Increase in resistance to airflow
Partial or complete obstruction
Trachea, Larger bronchi, Terminal and respiratory bronchioli
Restrictive Lung Diseases
Reduced expansion of lung parenchyma
Decreased total lung capacity
Chest wall disorders
Chronic interstitial and infiltrative diseases
Robbins Basic Pathology
Chronic Obstructive Pulmonary Diseases
Robbins Basic Pathology
EMPHYSEMA
Emphysema
Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles
Destruction of alveoli walls without significant fibrosis
Types of Emphysema
- Clinically significant airway obstruction
- Centriacinar emphysema
- 20x more common
- 95% of clinically significant cases
Centriacinar
Panacinar
Distal acinar
Irregular
distention of all the peripheral structures; later extends to respiratory bronchioles
dilation that initially affects the respiratory bronchioles
Robbins Basic Pathology
Centriacinar emphysema
Upper two thirds, apical segments
Dilation of air spaces and destruction of alveolar parenchyma
Autopsy Pathology: A Manual and Atlas
Centriacinar emphysema
Autopsy Pathology: A Manual and Atlas
Centriacinar emphysema: Central areas show marked emphysematous damage, surrounded by relatively spared alveolar spaces
Centriacinar (Centrilobular) Emphysema
Central, proximal parts of the acini
Respiratory bronchioles are affected
Distal alveoli are spared
Both emphysematous and normal air spaces exist within the same acinus and lobule
- More common and severe in the upper lobes, apical segments
- In severe cases distal acinus also involved
- Differentiation from panacinar emphysema becomes difficult
Cigarette smoking
Panacinar (Panlobular) emphysema
Autopsy Pathology: A Manual and Atlas
Panacinar emphysema: involving the entire pulmonary lobule
Panacinar (Panlobular) Emphysema
- Acini are uniformly enlarged
- From respiratory bronchiole to terminal blind alveoli
- More commonly in the lower lung zones, anterior margins
- Associated with
- α1-antitrypsin deficiency
Distal Acinar (Paraseptal) Emphysema
Proximal portion is normal
Distal part is primarily involved
More striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules
Occurs adjacent to areas of fibrosis, scarring, or atelectasis
More severe in the upper half of the lungs
Multiple, contiguous, enlarged air spaces
0.5 mm - >2.0 cm
Cystic structures
Progressive enlargement
Bullae
Cause is unknown
Most often in spontaneous pneumothorax in young adults
Irregular Emphysema
- Acinus is irregularly involved
- Associated with scarring
- Healed inflammatory diseases
- Clinically asymptomatic
- Most common form of emphysema
Pathogenesis of Emphysema
- Exposure to toxic substances
- Tobacco smoke, inhaled pollutants
- Ongoing inflammation
- Accumulation of neutrophils, macrophages and lymphocytes
- Elastases, cytokines (IL-8), oxidants are released
- Epithelial injury and proteolysis of the extracellular matrix
Emphysema
Elastin degradation products increase the inflammation
80% of patients with congenital α1-antitrypsin (antielastase) deficiency develop symptomatic panacinar emphysema
Earlier age and with greater severity if the affected person smokes
TGFB gene polymorphisms influence susceptibility to COPD
MMP-9 and MMP-12
Robbins Basic Pathology
Emphysema
Fibrosing lung diseases
- Tissue destruction without fibrosis
- Loss of epithelial and endothelial cells
- Also loss of mesenchymal cells
- Lack of extracellular matrix
- Emphysema can be thought as an insufficient wound repair
- **Tissue destruction with interstitial fibrosis **
- Excessive myofibroblastic or fibroblastic response to injury
- Scarring
Airway obstruction in emphysema
- Normally: Small airways are held open bu the elastic recoil of parenchyma
- Emphysema:
- Loss of elastic tissue
- During respiration respiratory bronchioles collapse
- Functional airway obstruction occurs, despite there is no mechanical obstruction
- There is also narrowing of lumen due to ongoing chronic inflammatory changes
Macroscopic appearance
- Panacinar emphysema
- Pale, voluminous lungs
- Obscure the heart when the anterior chest wall is removed at autopsy
- **Centriacinar emphysema **
- Upper two thirds of the lungs are more severely affected than the lower lungs
Histologic examination
- Destruction of alveolar walls without fibrosis, leading to enlarged air spaces
- Alveolar loss
- The number of alveolar capillaries is diminished
- Terminal and respiratory bronchioles deformed
- Loss of septa
- Collapse during expiration
- Bronchiolar inflammation and submucosal fibrosis in advanced disease
Robbins Basic Pathology
Conditions Related to Emphysema
- Compensatory emphysema
- Response to loss of lung substance
- Surgical removal of a diseased lung or lobe
- Obstructive overinflation
- Lung expands because air is trapped within it
- Tumor or foreign object
- Bullous emphysema
- Any form of emphysema produces large subpleural blebs or bullae
- Greater than 1 cm in diameter in the distended state
- May rupture, leading to pneumothorax
Bullous emphysema with large apical and subpleural bullae
Robbins Basic Pathology
Emphysematous bullae
Autopsy Pathology: A Manual and Atlas
- Mediastinal (interstitial) emphysema
- Air enters the connective tissue stroma of the lung, mediastinum, and subcutaneous tissue
- Spontaneously with a sudden increase in intra-alveolar pressure →
tear → air enters into tissue
- vomiting or violent coughing
- children with whooping cough
- patients on respirators who have partial bronchiolar obstruction
- perforating injury
Interstitial pulmonary emphysema
Autopsy Pathology: A Manual and Atlas
CHRONIC BRONCHITIS
Chronic Bronchitis
Clinical definition: Persistant cough with sputum, at least 3 months, at least 2 consecutive years, absence of any identifiable cause
Cigarette smokers
Urban, smog-ridden cities
20-25% of men in 40-65-year-old age have the disease
- Hypersecretion of mucus
- Beginning in the large airways
- Hypertrophy of mucous glands in the trachea and main bronchi
- Increase in mucin-secreting goblet cells in the surface epithelium of smaller bronchi and bronchioles
- Inflammation with infiltration of CD8+ lymphocytes, macrophages, and
neutrophils
- **No eosinophils in contrast to asthma **
- Mucus hypersecretion is primarily a reflection of large bronchial involvement
- Morphologic basis of airflow obstruction in chronic bronchitis is more peripheral:
- Small airway disease
- Goblet cell metaplasia
- Mucous plugging of the bronchiolar lumen
- Inflammation, and bronchiolar wall fibrosis
- Coexistent emphysema
- Chronic bronchiolitis
- Almost always complicated by emphysema
- Effects of environmental irritants
- T cell cytokines –> IL-13
- Transcription of the mucin gene MUC5AC in bronchial epithelium
- Production of neutrophil elastase
- Microbial infection has a secondary role
Chronic bronchitis: Marked thickening of the mucous gland layer (approximately twice-normal) and squamous metaplasia of lung epithelium
Robbins Basic Pathology
-
Mucosal lining of the larger airways
- hyperemic and swollen by edema fluid
- covered by a layer of mucinous or mucopurulent secretions
-
Smaller bronchi and bronchioles
- filled with similar secretions
-
The diagnostic feature of chronic bronchitis in the trachea and larger bronchi → enlargement of the mucus-secreting glands
- Reid index increased
- Ratio of the thickness of the submucosal gland layer to that of the bronchial wall
- normally 0.4
- Reid index increased
-
Inflammatory cells, largely mononuclear, neutrophils
-
Chronic bronchiolitis
- Small airway disease
- Goblet cell metaplasia
- Mucous plugging, inflammation, and fibrosis
-
Bronchiolitis obliterans
- Severe cases
- **Complete obliteration of the lumen as a consequence of fibrosis **
- Submucosal fibrosis leads to luminal narrowing and airway obstruction
- Changes of emphysema co-exist