Pathology - Lecture 2 (the Obstructive Diseases ) Flashcards
Obstructive lung disease general features
-airway disorder
-increased resistance
-reduced FEV1:FVC (FEV1 markedly reduced )
-hypo email and hypercapnia
Emphysema
Irreversible enlargement of airspaces distal to the terminal bronchioles (respiratory acinus) accompanied by destruction of the alveolar walls
• Centriacinar emphysema
• Respiratory bronchiole (RB) is affected, and distal alveoli are spared
• Upper lung zones
• Most common
Panacinar emphysema
Respiratory bronchiole (RB) to terminal alveoli are affected
• Alpha-1 antitrypsin deficiency
• Lower lung zones
Para-septal (distal acinar):
Next to atelectasis, along septa, subpleural
• Rare
• More common in upper lobes
• May form bullae
• Can lead to pneumothorax
Irregular (paracicatricial)
-Surrounding scar
• Asymptomatic – incidental finding
Pathogenesis of emphysema
• Destruction of elastic fibers in the alveoli due to inflammatory mediators released by smoke.
• Genetic predisposition( Alpha-1- antitrypsin deficiency)
Alpha-1 antitrypsin (A1AT) deficiency
-• Point mutation in the Pi gene on chromosome 14
-Defect in the synthesis of alpha-1 antitrypsin by the liver, misfolding the protein and failing to release it into the circulation
-panacinar emphysema
-younger ages
What are the pathological features of emphysema (micro and gross )
Gross : hyper-inflated lungs , parenchyma is moth eaten appearance
Micro - destruction of alveolar septa , over distended alveolar spaces
Clinical features of emphysema
• Expiratory dyspnea which is insidious in onset and progressive
• Barrel-chest (increased antero-posterior diameter of the chest)
• Sitting in a forward hunched position trying to squeeze air out of the lungs
• Prolonged expiration through pursed lips
• Weight loss
Complications of emphysema
• Pulmonary hypertension & cor pulmonale – very rare and terminal
- Absence of cyanosis + breathing through pursed lips: “Pink puffers”
Chronic Bronchitis
• Persistent cough with mucoid sputum
• For at least 3 months
• In the past 2 consecutive years
• In the absence of any other identifiable cause
Pathogenesis of chronic bronchitis
-smokers and urban dwellers
- Submucosal gland hypertrophy – Hypersecretion of mucus(NB)
- Goblet cell metaplasia in bronchioles
- Smooth muscle hyperplasia and peribronchiolar fibrosis – small airway obstruction distally
- Inflammation: Infiltrate of CD8+ T-cells, macrophages and neutrophils → eventually
fibrosis (no eosinophils in contrast to asthma) - Small airway obstruction due to fibrosis and mucus plugging
Grossly and microscopically describe chronic bronchitis
Gross - •Hyperemia and edema of mucous membranes •Excessive mucinous or mucopurulent secretions
Microscopy :
-thickening of mucus gland layer
-goblet cell hyperplasia
-chronic inflammation and fibrosis
-squamous metaplasia
Complications of chronic bronchitis
-secondary infections
-Over time → Pulmonary hypertension and cor pulmonale
-Peripheral edema + cyanosis: “Blue bloaters”
Bronchiectasis
• Destruction of smooth muscle and elastic tissue by inflammation
• Stemming from persistent or severe infections
• Leads to permanent dilation of bronchi and bronchioles
Bronchiestatsis etiology
-bronchial obstruction (tumor ,foreign body)
-suppurative pneumonia (virulent organisms )
-congenital/hereditary conditions that lead to chronic infections
Bronchiectasis Gross Appearance
• Usually affects the lower lobes bilaterally, particularly those air passages that are most vertical
• Cut surface of lung shows markedly dilated bronchi that extend to subpleural regions, some filled with mucopurulent material
Bronchiectasis micro
- Squamous metaplasia of bronchial epithelium
- Intense acute and chronic inflammatory exudate
in bronchial walls, necrotizing ulceration - Fibrosis of bronchiolar walls leading to
bronchiolitis obliterans - Lung abscesses may be present
What are the clinical features you’d see in Bronchiectasis
-Severe persistent cough, fever
• Expectoration of foul smelling, sometimes bloody sputum (hemoptysis)
-symptoms usually episodic and they worsen with infections
-• Paroxysms of cough particularly frequent when the patient rises in the morning
→ change in position causes collections of pus and secretions to drain into the
bronchi
Complications of Bronchiectasis
-sepsis and brain abscess
-pulmonary hypertension and cor pulmonale
-systemic amyloidosis
Primary Ciliary Dyskinesia
-AR disease
-mutations in cilia gene leads bronchiectasis
Kartagener syndrome:
-a subset of primary ciliary dyskinesia
- bronchiectasis (defective mucociliary clearance)
- dextrocardia (defective movement of the organs during embryogenesis) 3. sinusitis (impaired mucociliary clearance → recurrent sinus infections)
Bronchial asthma
Heterogeneous disease characterized by:
• Chronic airway inflammation
• Variable expiratory airflow obstruction
How is bronchial asthma classified
- Atopic: Evidence of allergen sensitization and immune activation
- Non-atopic: No evidence of allergen sensitization
Atopic asthma - Allergic sensitization
Inhaled allergen taken up by dendritic cell then presented to Th2 which activates
-IL4(stimulates B cell to produce IgE which binds to Fc receptors on mast cells )
-IL5 (eosinophils )
-IL13 (mucus production)
Atopic Asthma - immediate phase
-reexposure of antigen
-IgE cross links with Fc receptors on mast cells
-mast cell granulation (histamines and leukotrienes )
-Vagal stimulation - activates M receptors and causes bronchoconstriction
Atopic Asthma - late phase
-Inflammatory mediators stimulate epithelial cells to produce chemokines e.g. eotaxin
-Recruitment of TH2 cells, eosinophils, other leukocytes
-Amplification of inflammatory reaction initiated by resident immune cells
-Eosinophils release major basic protein which causes damage to the epithelium epithelial detachment from
basement membran
Complications of atopic asthma
Airway remodeling
What are features of airway remodeling
-thickening of airway wall
-sub basement membrane fibrosis
-increased vascularity
-increased in the number and size of submucosal glands
-goblet cell hyperplasia
-Hypertrophyand/orhyperplasiaofthebronchialwallsmoothmuscle
Non atopic Asthma
• No evidence of sensitization
• Serum IgE = normal
• Viral infections of upper respiratory tract or inhaled irritants like: SO2, NO2,
and O3
• Virus-induced mucosal damage à lowers threshold of subepithelial vagal
receptors to irritants
• Inflammatory mediators are the same as atopic asthma
• Treatment is similar
Aspirin-sensitive asthma
-Occurs in individuals with recurrent rhinitis and nasal polyps
- Mechanism: Inhibits cyclo-oxygenase (COX) pathway of arachidonic acid without affecting lipo-oxygenase routeàbronchoconstriction mediated by
leukotrienes
Gross features of bronchial asthma
In patients dying of acute severe asthma
• Occlusion of airways by thick mucus plugs
• Hyperinflation of lungs
Microscopy of the sputum or bronchoalveolar in asthma
- Curschmann spirals: cleared mucus plugs containing whorls of shed
epithelium - Charcot-Leyden crystals: crystalloids made up of the eosinophil proteins
• Features of airway remodeling
Bronchial biopsy from asthmatic patient
sub-basement membrane fibrosis, eosinophilic inflammation and smooth muscle hyperplasia
