Pathology - Lecture 2 (the Obstructive Diseases )

Question 1

Obstructive lung disease general features

Answer 1

-airway disorder
-increased resistance
-reduced FEV1:FVC (FEV1 markedly reduced )
-hypo email and hypercapnia

Question 2

Emphysema

Answer 2

Irreversible enlargement of airspaces distal to the terminal bronchioles (respiratory acinus) accompanied by destruction of the alveolar walls

Question 3

• Centriacinar emphysema

Answer 3

• Respiratory bronchiole (RB) is affected, and distal alveoli are spared
• Upper lung zones
• Most common

Question 4

Panacinar emphysema

Answer 4

Respiratory bronchiole (RB) to terminal alveoli are affected
• Alpha-1 antitrypsin deficiency
• Lower lung zones

Question 5

Para-septal (distal acinar):

Answer 5

Next to atelectasis, along septa, subpleural
• Rare
• More common in upper lobes
• May form bullae
• Can lead to pneumothorax

Question 6

Irregular (paracicatricial)

Answer 6

-Surrounding scar
• Asymptomatic – incidental finding

Question 7

Pathogenesis of emphysema

Answer 7

• Destruction of elastic fibers in the alveoli due to inflammatory mediators released by smoke.
• Genetic predisposition( Alpha-1- antitrypsin deficiency)

Question 8

Alpha-1 antitrypsin (A1AT) deficiency

Answer 8

-• 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

Question 9

What are the pathological features of emphysema (micro and gross )

Answer 9

Gross : hyper-inflated lungs , parenchyma is moth eaten appearance
Micro - destruction of alveolar septa , over distended alveolar spaces

Question 10

Clinical features of emphysema

Answer 10

• 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

Question 11

Complications of emphysema

Answer 11

• Pulmonary hypertension & cor pulmonale – very rare and terminal
- Absence of cyanosis + breathing through pursed lips: “Pink puffers”

Question 12

Chronic Bronchitis

Answer 12

• Persistent cough with mucoid sputum
• For at least 3 months
• In the past 2 consecutive years
• In the absence of any other identifiable cause

Question 13

Pathogenesis of chronic bronchitis

Answer 13

-smokers and urban dwellers

1. Submucosal gland hypertrophy – Hypersecretion of mucus(NB)
2. Goblet cell metaplasia in bronchioles
3. Smooth muscle hyperplasia and peribronchiolar fibrosis – small airway obstruction distally
4. Inflammation: Infiltrate of CD8+ T-cells, macrophages and neutrophils → eventually
   fibrosis (no eosinophils in contrast to asthma)
5. Small airway obstruction due to fibrosis and mucus plugging

Question 14

Grossly and microscopically describe chronic bronchitis

Answer 14

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

Question 15

Complications of chronic bronchitis

Answer 15

-secondary infections
-Over time → Pulmonary hypertension and cor pulmonale
-Peripheral edema + cyanosis: “Blue bloaters”

Question 16

Bronchiectasis

Answer 16

• Destruction of smooth muscle and elastic tissue by inflammation
• Stemming from persistent or severe infections
• Leads to permanent dilation of bronchi and bronchioles

Question 17

Bronchiestatsis etiology

Answer 17

-bronchial obstruction (tumor ,foreign body)
-suppurative pneumonia (virulent organisms )
-congenital/hereditary conditions that lead to chronic infections

Question 18

Bronchiectasis Gross Appearance

Answer 18

• 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

Question 19

Bronchiectasis micro

Answer 19

1. Squamous metaplasia of bronchial epithelium
2. Intense acute and chronic inflammatory exudate
   in bronchial walls, necrotizing ulceration
3. Fibrosis of bronchiolar walls leading to
   bronchiolitis obliterans
4. Lung abscesses may be present

Question 20

What are the clinical features you’d see in Bronchiectasis

Answer 20

-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

Question 21

Complications of Bronchiectasis

Answer 21

-sepsis and brain abscess
-pulmonary hypertension and cor pulmonale
-systemic amyloidosis

Question 22

Primary Ciliary Dyskinesia

Answer 22

-AR disease
-mutations in cilia gene leads bronchiectasis

Question 23

Kartagener syndrome:

Answer 23

-a subset of primary ciliary dyskinesia

1. bronchiectasis (defective mucociliary clearance)
2. dextrocardia (defective movement of the organs during embryogenesis) 3. sinusitis (impaired mucociliary clearance → recurrent sinus infections)

Question 24

Bronchial asthma

Answer 24

Heterogeneous disease characterized by:
• Chronic airway inflammation
• Variable expiratory airflow obstruction

Question 25

How is bronchial asthma classified

Answer 25

• Atopic: Evidence of allergen sensitization and immune activation
• Non-atopic: No evidence of allergen sensitization

Question 26

Atopic asthma - Allergic sensitization

Answer 26

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)

Question 27

Atopic Asthma - immediate phase

Answer 27

-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

Question 28

Atopic Asthma - late phase

Answer 28

-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

Question 29

Complications of atopic asthma

Answer 29

Airway remodeling

Question 30

What are features of airway remodeling

Answer 30

-thickening of airway wall
-sub basement membrane fibrosis
-increased vascularity
-increased in the number and size of submucosal glands
-goblet cell hyperplasia
-Hypertrophyand/orhyperplasiaofthebronchialwallsmoothmuscle

Question 31

Non atopic Asthma

Answer 31

• 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

Question 32

Aspirin-sensitive asthma

Answer 32

-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

Question 33

Gross features of bronchial asthma

Answer 33

In patients dying of acute severe asthma
• Occlusion of airways by thick mucus plugs
• Hyperinflation of lungs

Question 34

Microscopy of the sputum or bronchoalveolar in asthma

Answer 34

1. Curschmann spirals: cleared mucus plugs containing whorls of shed
   epithelium
2. Charcot-Leyden crystals: crystalloids made up of the eosinophil proteins
   • Features of airway remodeling

Question 35

Bronchial biopsy from asthmatic patient

Answer 35

sub-basement membrane fibrosis, eosinophilic inflammation and smooth muscle hyperplasia