7. Obstructive Pulmonary Diseases Flashcards
Definition of obstructive pulmonary diseases
Obstructive airway diseases characterized by an increase in resistance to airflow due to partial or complete obstruction at any level; pulmonary function test usually show a decreased expiratory function (decreased maximal airflow rates during forced expiration) & an increase in total lung volume (barrel chest)
Types of obstructive pulmonary diseases
- Bronchiectasis
- Bronchial asthma
- Emphysema
- Chronic bronchitis
Definition of bronchiectasis
A chronic necrotizing inflammation of the bronchi & bronchioles leading to or associated with abnormal permanent dilation of these airways
Causes of bronchiectasis
- Congenital or hereditary conditions
- Cystic fibrosis
- Intralobar pulmonary sequestration
- Kartagener syndrome (aka immotile ciliary syndrome or primary ciliary dyskinesia; autosomal recessive disorder resulting in a defect in the action of cilia lining the respiratory tract & fallopian tubes; presents with triad of bronchiectasis, chronic sinusitis & situs inversus – congenital condition whereby major visera are mirrored from their normal positions) - Post-infection conditions
- Post-pneumonia
- Post-pulmonary tuberculosis - Bronchial obstruction
- Due to tumour, foreign bodies etc
- Bronchiectasis in such cases will be isolated to the
obstructed lung segment - Immune-mediated
- Rheumatoid arthritis, SLE, inflammatory bowel disease, post-transplantation
Pathogenesis of bronchiectasis
- Obstruction coupled with infection produces necrotizing
inflammatory reactions
- Destroys smooth muscle & elastic tissue
- Weakens bronchial wall
- Leads to permanent dilation of the bronchi & bronchioles involved - Bronchiectasis may be generalized or localized:
- Localized bronchiectasis: mechanical obstruction of an airway, childhood bronchopulmonary infections
- Generalized bronchiectasis: inherited conditions, acquired impairment of host defences against respiratory infections
Morphology of bronchiectasis
- [Gross]
- Saccular, cylindrical or irregular dilation of bronchi
- Bronchi contain thick mucopurulent secretions - [Histology]
- Loss of bronchial wall smooth muscle & elastic tissue
- Inflammation, lymphoid aggregates
- Goblet cell metaplasia & squamous metaplasia of bronchial epithelium
- Fibrosis of parenchyma
Pathological Effects & complications of bronchiectasis
- Cor pulmonale
- Chronic suppurative inflammation
- Lung abscess
- Pyemia predisposing to brain abscess
- Systemic amyloidosis
Clinical features of bronchiectasis
- Persistent cough, foul-smelling sputum
- Dyspnea, orthopnea
- Fever
- Clubbing
Definition of bronchial asthma
Chronic inflammatory disorder of the airways that is characterized by increased airway responsiveness to a variety of stimuli, resulting in episodic small airway obstruction due to reversible bronchoconstriction, inflammation of the bronchial walls & increased mucus secretion
Forms of asthma
- Allergic/Atopic Asthma (extrinsic)
- Non-atopic Asthma (intrinsic)
- Occupational Asthma (extrinsic)
Allergic/Atopic Asthma (extrinsic)
- Type I hypersensitivity reaction (IgE-mediated)
- Most common in children, typically with a personal or family history of allergy
- Triggered by allergens (e.g. pollen, dust)
Non-atopic Asthma (intrinsic)
- Caused by prior airway inflammation (non-allergic)
which is postulated to lower the threshold of the subepithelial vagal receptors to irritants, hence resulting in a state of hyperirritability - Triggered by respiratory viral infections, inhalation of environmental pollutants (SO2, NO2, O3), stress, cold, exercise
Occupational Asthma (extrinsic)
- Due to a variety of mechanisms depending on inciting agent (e.g. Type I hypersensitivity reaction, direct liberation of bronchoconstricting substances)
- Triggered by inhalation of organic & chemical dusts, fumes, & other chemicals
Pathogenesis of allergic asthma
- Type I hypersensitivity reaction (2 phases)
- Early phase reaction due to induction of TH2 cells which secrete a variety of cytokines which results in bronchoconstriction & mucus secretion
- Late phase reaction due to recruitment of leukocytes which secrete more factors & cytokines to cause another bout of epithelial damage and airway narrowing - Airway remodelling
- Due to repeated bouts of allergen exposure &
immune reactions which result in structural changes
of the bronchial wall
- Hypertrophy & hyperplasia of bronchial smooth
muscle, epithelial injury, increased airway vascularity, subepithelial mucus gland hypertrophy & hyperplasia, deposition of subepithelial collagen
Morphology of bronchial asthma
[Gross]
- Mucosal & submucosal edema
- Leukocytic infiltrate (eosinophils, mast cells, lymphocytes)
- Epithelial cell necrosis
- Bronchial wall fibrosis
[Histology]
- Charcot-leyden crystals: Derived from eosinophil granules (galectin-10, a lysophospholipase binding protein)
- Curschmann spirals: Mucous plugs from small airways containing whorls of shed epithelium
- Creola bodies: Clusters of epithelial cells
Pathological effects & complications of bronchial asthma
Status asthmaticus
- A state of unremitting attacks which can persist for days to weeks, leading to respiratory insufficiency & eventual death
- Such patients typically have a long history of asthma
Definition of emphysema
Permanent dilation of air spaces distal to the terminal bronchiole (acinus) with destruction of their walls, without fibrosis; clinically grouped with Chronic Bronchitis and collectively referred to as “Chronic Obstructive Pulmonary Disease” (COPD)
Types of emphysema
- Centriacinar (Centrilobular) Emphysema
- Panacinar (Panlobular) Emphysema
- Distal Acinar (Paraseptal) Emphysema
- Other Emphysemas (loose use of the term)
- Compensatory emphysema
- Scar emphysema
Centriacinar (Centrilobular) Emphysema
- Central/proximal parts of acinus affected (affects proximal respiratory bronchioles, spares alveoli)
- Usually occurs in the apical regions of upper lobes
- Found in smokers, often in associated with chronic bronchitis
Panacinar (Panlobular) Emphysema
- Acinus is uniformly enlarged, from the respiratory bronchiole to the terminal alveoli (affects both respiratory bronchioles & alveoli)
- Usually occurs in the lower zones & anterior margins of the lung
- Found in individuals with alpha1-antitrypsin deficiency
Distal acinar (paraseptal) emphysema
- Distal parts of the acinus affected (affects alveoli,
spares respiratory bronchioles) - Usually occurs in the upper half of the lungs,
adjacent to areas of fibrosis, scarring or atelectasis - May lead to sub pleural bull which can rupture, leading to spontaneous pneumothorax (commonly seen in adults)
Compensatory emphysema
Dilation of alveoli without destruction of septal walls as a compensatory response to loss of lung substance elsewhere
Scar emphysema
Irregular involvement of acini, associated with scarring
Causes of emphysema
- Cigarette smoking
- Atmospheric pollution
- Chronic bronchitis
- Pneumoconiosis
- alpha1-antitypsin deficiency
Pathogenesis of emphysema
- Normal connective tissue modeling is governed by a
delicate protease-antiprotease balance
- Neutrophil proteases (e.g. elastase) are released at
sites of inflammation
- Serum alpha1-antitrypsin is a major inhibitor of proteases - Inflammation due to various causes results in an increase in proteases liberated locally
- Decreased levels of alpha1-antitrypsin results in impaired inhibition of proteases
- Congential deficiency of alpha1-antitrypsin
- Acquired functional deficiency of alpha1-antitrypsin
(inactivated by reactive oxygen species, produced as a result of inflammation or directly from cigarette smoke) - Additionally, alveolar macrophages also release macrophage elastase (which is not inhibited by alpha1-antitrypsin) during the inflammatory process
- Collectively, increased protease liberation & decreased alpha1-antitrypsin levels results in destruction of elastic tissue, which results in:
- Destruction of alveolar walls, resulting in fusion of alveoli into large abnormal air spaces (if near pleural surface, appears grossly as blebs & bullae)
- Premature collapse of bronchioles during expiration (as they are usually tethered by elastic recoil of the lung, which diminishes with elastic tissue destruction), resulting in air-trapping
Morphology of emphysema
[Gross]
- Voluminous (due to air trapping)
- Pale (due to vessel compression)
- Blebs & bullae (air-filled spaces)
[Histology]
- Dilation of alveolar spaces
- Destruction of septal walls
- Fusion of alveoli
- Compression or distortion of bronchioles & vasculature by large abnormal air spaces
Pathological effects & complications of emphysema
- Cor pulmonale (due to destruction of vasculature with the destruction of the alveolar walls & compression of remaining vasculature by large abnormal air spaces)
- Respiratory failure
- Pneumothorax (due to rupture of bullae)
- Increased incidence of peptic ulcer (postulated to be
secondary to hypercapnia which induces increased gastric acid secretion)
Clinical features of emphysema
- “Pink puffers”
- Barrel-chested (due to air trapping)
- Dyspneic, with obviously prolonged expiration
- Breaths through pursed lips (to help maintain positive
airway pressure)
Definition of chronic bronchitis
Clinically defined as persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause; clinically grouped with Emphysema and collectively referred to as “Chronic Obstructive Pulmonary Disease” (COPD)
Causes of chronic bronchitis
- Cigarette smoking (main cause)
- Air pollution
- Toxic industrial inhalants
- Respiratory infections
Pathogenesis of chronic bronchitis
- Mucus hypersecretion as a result of:
- Stimulation by neutrophil proteases
- Mucus gland hypertrophy
- Marked increased in goblet cells in small airways - Mucus plugs then produce airway obstruction
- Role of infection appears to be secondary
- Not responsible for initiation of chronic bronchitis
- But probably significant in maintaining & exacerbating it
Morphology of chronic bronchitis
- Hypertrophy & hyperplasia of mucous gland layer, resulting in an increased ratio of thickness of the mucous gland layer to that of the entire bronchial wall (Reid index, normally = 0.5)
- Excess mucus in the airways
- Increase in the number of goblet cells
- Increased amount of smooth muscle
- Lymphocytic infiltrate
- May exhibit squamous metaplasia & dysplasia
Pathological Effects & complications of chronic bronchitis
- Respiratory failure
- Cor pulmonale (as air trapping in obstructed segments
produce increased pressure which compressed
pulmonary vessels) - Respiratory infections (due to accumulation of mucus)
- Malignancy (due to atypical metaplasia & dysplasia)
Clinical features of chronic bronchitis
- “Blue bloaters”
- Mild cyanosis, dyspnea
- Persistent productive of sputum
