Respiratory System Pathology 2 - Galbraith lecture

Question 1

Characteristics of Obstructive Lung diseases

Answer 1

Increased resistance to airflow due to partial or complete obstruction from level of trachea to larger bronchi to terminal and respiratory bronchioles

decreased maximal flow rates during forced expiration (FEV1/FVC less than 0.7)

Question 2

Obstructive lung diseases

Answer 2

Emphysema
Chronic bronchitis
Asthma
Bronchiectasis
COPD

Question 3

COPD incidence

Answer 3

Women, african americans

Smoking
environmental/occupational pollutants

Question 4

Emphysema

Answer 4

destruction of airway walls and irreversible enlargement of airways distal to the terminal bronchiole

Classification based on site of involvement within pulmonary acinus

• Centriacinar
• Panacinar
• Distal acinar
• Irregular

Question 5

Centriacinar emphysema

Answer 5

heavy smokers
often with COPD

respiratory bronchioles involved, spares distal alveoli

upper lobes/apical segments

Question 6

Panacinar emphysema

Answer 6

a1-antitrypsin deficiency

alveoli distal to respiratory bronchioles involved

lower and anterior aspects of lungs (bases most severely involved)

Question 7

Emphysema pathogenesis

Answer 7

Exposure to injurious particles in tobacco smoke stimulates inflammation
-IL8, TNF recruit inflammatory cells

Imbalance of proteases and antiproteases
-inflammatory cells release elastase

Oxidative stress
-smoke, inflammatory cell oxidants, continuing cycle of tissue damage and inflammation

Question 8

Pathways of smoking and genetic predisposition leads to alveolar wall destruction

Answer 8

• oxidative stress, increased apoptosis and senescence
• inflammatory cells, release of inflammatory mediators
• protease-antiprotease imbalance
• complicated by congenital a1-antitrypsin deficiency

Question 9

a1-antitrypsin deficiency

Answer 9

a1-antitrypsin potent antiprotease

Pi locus on Ch14

Homozygotes for Z allele have significant decrease in a1-antitrypsin

80% PiZZ develop symptomatic panacinar emphysema, accelerated and more severe if pt smokes

Cirrhosis, emphysema risk

Question 10

Emphysema as an obstructive lung disease

Answer 10

small airways normally open by elastic recoil of lung parenchyma

Destruction of elastic alveolar walls surrounding respiratory bronchioles –> collapse of bronchioles during expiration

Question 11

Clinical course of emphysema

Answer 11

No symptoms until 1/3 of lung tissue is affected

Initial symptoms: dyspnea, cough, wheezing

Lean forward, and breath out with pearced lips

Severe: weight loss, barrel chest - overdistension, prolonged expiration, “pink puffer” due to over ventilation

May progress to pulmonary HTN and right sided failure

Question 12

Death causes in emphysema

Answer 12

CAD
Respiratory failure
RHF
Pneumothorax –> lung collapse

Question 13

Chronic bronchitis

Answer 13

Chronic, persistent productive cough without other identifiable cause

smokers, inhabitants of polluted environments

Question 14

Pathogenesis of chronic bronchitis

Answer 14

Initiating factor: exposure of bronchi to inhaled irritants

mucus hyper secretion

Chronic inflammation –> damage and fibrosis of small airways

Diminished ciliary action of respiratory epithelium, leading do stasis of mucus

Question 15

Morphology of chronic bronchitis

Answer 15

edema and swelling of respiratory mucosa with squamous metaplasia

Hyperplasia of submucosal mucous glands of trachea and larger bronchi
-thickness of mucus gland layer increases

Increased goblet cells in small bronchi and bronchioles and extensive small airway mucous plugging

Question 16

Clinical course of chronic bronchitis

Answer 16

Persistent productive cough

dyspnea on exertion

Hypercapnia, hypoxia, mild cyanosis (“blue bloater”)

Question 17

Asthma

Answer 17

Chronic disorder of conducting airways

• recurrent bronchoconstriction
• inflammation of bronchial walls
• increased mucus secretion

Symptoms:

• recurrent wheezing, SOB, chest tightness, cough
• more frequent at night/early morning

Question 18

Atopic asthma

Answer 18

Type I - IgE mediated hypersensitivity reaction

Onset in childhood

high serum IgE, positive skin test for inciting allergen, or IgE Abs to specific allergens

FHx of asthma

Question 19

Atopic asthma pathogenesis

Answer 19

Th2 sensitization to allergen stimulates IgE production of IL4, IL 13 recruiting eosinophils (IL5), stimulates mucus production (IL13)

IgE binds to Fc receptors on mast cells
-reexposure cross links IgE on mast cells –> degranuation and immediate hypersensitivity reaction

Question 20

Immediate phase of atopic asthma hypersensitivity reaction

Answer 20

Minutes

bronchoconstriction
mucous secretion
Increased vascular permeability

Question 21

Late phase of atopic asthma hypersensitivity reaction

Answer 21

recruitment of more inflammatory cells (neutrophils, eosinophils, lymphocytes)
–> damage to mucosal tissue

Question 22

Non-atopic asthma

Answer 22

Bronchoconstriction triggered by varied stimuli:

• respiratory viruses
• inhalation of irritants (smoke)
• cold air
• exercise

Question 23

Morphology of asthma

Answer 23

Repeated allergen exposure and reaction induces “airway remodeling”

• Bronchial wall sm. m. hypertrophy and hyperplasia
• Subepithelial fibrosis
• Submucosal gland hyperplasia, increased goblet cells
• increased airway vascularity
• increased thickness of airway wall

Severe cases: bronchi and bronchioles occluded by thick mucus plugs

• expelled in sputum or BAL specimens (Curshmann spirals)
• contain numerous eosinophils and Charcot-Leyden crystals (atopic cases)

Question 24

Clinical course of asthma

Answer 24

Acute asthma attack may last hours, lower baseline level constantly

Severe acute asthma - status asthmaticus - attack lasts for days, result in obstruction sufficient to cause death

Question 25

Bronchiectasis

Answer 25

Chronic recurrent necrotizing infections destroy smooth muscle and elastic tissue –> permanent dilation of bronchi and bronchioles

Infection with assoc. inflammation and destruction may follow obstruction and impedance of normal drainage

severe bronchial infections may cause enough inflammatory damage and necrosis to bring about bronchiectatic changes

Question 26

Predisposing conditions for bronchiectasis

Answer 26

conditions affecting mucus clearing:

• primary ciliary dyskinesia
• cystic fibrosis
• other bronchial obstruction

immunodeficiency conditions

Question 27

Peribronchial fibrosis

Answer 27

result of repeated attempts to resolve inflammatory process

may be extensive enough to obliterate nearby bronchioles
-bronchiolitis obliterans

Question 28

Cystic fibrosis genetic cause

Answer 28

abnormal function or lack of epithelial Cl- channel - cystic fibrosis transmembrane conductance regulator

CFTR gene on Ch7

Question 29

CTFR

Answer 29

Transports Cl-

• in sweat glands, from the surface into the cell
• other epithelia from cell to lumen

Normally inhibits ENaC - found on epithelial cell apical surfaces, except in sweat glands

Lack of functioning CTFR –> overactive ENaC, resulting in epithelia taking up sodium ions and water passively following

Question 30

Cystic fibrosis

Answer 30

Deficient hydration of airway mucus leads to defective ciliary activity

leads to inability to clear mucus and any pathogenic microbes

Chronic infection ensues –> eventual bronchiectasis

Question 31

Infections common in CF

Answer 31

S. aureus
H. influenzae
Burkholderia cepacia

Pseudomonas aeruginosa
-produce mucoid capsule (alginate) which allows it to form a protective biofilm