Pathology of Obstructive Lung Disease

Question 1

obstructive lung diseases - overview

Answer 1

*disorders associated with AIRFLOW OBSTRUCTION
*increased resistance to air flow caused by partial/complete airway obstruction
*lung cannot empty due to air trapping, leading to increased lung capacity
*PFT: DECREASED FEV1/FVC RATIO (<0.7 or <LLN)

Question 2

major obstructive lung diseases

Answer 2

1. asthma
2. COPD
3. bronchiectasis

Question 3

asthma - overview

Answer 3

*chronic inflammatory disorder with episodic/reversible bronchospasm associated with airway obstruction

Question 4

atopic asthma - overview

Answer 4

*atopic = evidence of allergen sensitization
*classic IgE-mediated (type I) hypersensitivity
*most common form of asthma
*begins in childhood with positive family history and skin test
*triggered by ENVIRONMENTAL ANTIGENS

Question 5

non-atopic asthma - overview

Answer 5

*nonatopic = no evidence of allergen sensitization
*no family history
*triggered by VIRAL RESPIRATORY INFECTIONS or INHALED POLLUTANTS
*may have innocuous triggers (cold, exercise)

Question 6

pathogenesis of asthma

Answer 6

1. trigger:
   -Th2 response (inhaled allergens)
   -IL4 → IgE → binds submucosal mast cells
   -IL5 activates eosinophils
   -IL13 stimulates mucous production
2. immediate phase (minutes):
   -mast cell response
   ~bronchospasm: vagal receptor stimulation
   ~edema: increased vascular permeability
   ~mucous production
   ~inflammation: eosinophil recruitment
3. late phase (hours):
   -eosinophil response
   -eosinophil factors cause epithelial damage (especially GALECTIN-10)

Question 7

asthma - morphology

Answer 7

*occluded bronchi/bronchioles by thick, tenacious mucous plugs; contain whorls of shed epithelium (Curshmann spirals)
*numerous eosinophils and Charcot-Leyden crystals
*airway remodeling (irreversible):
-thickening of airway wall with submucosal fibrosis
-increased submucosal vascularity
-increase in the size of submucosal glands
-GOBLET CELL METAPLASIA
-HYPERTROPHY OF BRONCHIOLE SMOOTH MUSCLE

Question 8

what is this? what disorder is it associated with?

Answer 8

*Curschmann spirals
*whorls of shed epithelium found in mucous plugs that are occluding the bronchioles
*associated with ASTHMA

Question 9

what is this? what disorder is it associated with?

Answer 9

*Charcot-Leyden crystals
*EOSINOPHILIC, hexagon, double-pointed crystals formed by breakdown of eosinophils in sputum
*associated with ASTHMA

Question 10

Curschmann spirals in asthma

Answer 10

*whorls of shed epithelium found in mucous plugs that are occluding the bronchioles

Question 11

Charcot-Leyden crystals in asthma

Answer 11

*EOSINOPHILIC, hexagon, double-pointed crystals formed by breakdown of eosinophils in sputum

Question 12

airway remodeling in asthma

Answer 12

*irreversible
*thickening of airway wall with submucosal fibrosis
*increased submucosal vascularity
*increase in the size of submucosal glands
*GOBLET CELL METAPLASIA
*HYPERTROPHY OF BRONCHIOLE SMOOTH MUSCLE

Question 13

COPD - overview

Answer 13

*airway obstruction and alveolar abnormalities caused by inhalation of noxious particles or gases
*parenchymal destruction AND airway disease
*airflow limitation caused by combination:
1. MECHANICAL obstruction by mucous secretions
2. FUNCTIONAL obstruction from parenchymal damage
*PFTs: reduced FEV1, normal or near-normal FVC, REDUCED FEV1/FVC RATIO (<0.7 or <LLN)

Question 14

chronic bronchitis - overview

Answer 14

*persistent productive cough for > 3 consecutive months in > 2 consecutive years
*clinical features:
-productive cough
-HYPERCAPNIA, HYPOXEMIA, MILD CYANOSIS (blue bloaters)
-mucus plugs trap CO2 → increased PaCO2 and decreased PaO2
*radiologic features are non-specific

Question 15

chronic bronchitis - pathogenesis

Answer 15

*mucous hypersecretion in large airways
*inflammation → inflammatory mediators histamine and IL13
*smoking → acquired CFTR dysfunction (dehydrated mucus)

Question 16

chronic bronchitis - gross pathology

Answer 16

*hyperemia, swelling, and edema of epithelium
*EXCESSIVE MUCOPURULENT SECRETIONS
-heavy casts of pus secretions fill bronchi/bronchioles

Question 17

chronic bronchitis - microscopic pathology

Answer 17

*HYPERTROPHY/HYPERPLASIA OF BRONCHIAL MUCIN GLANDS
*inflammation and fibrosis:
-lymphocytes, macrophages, and neutrophils seen in bronchial mucosa

Question 18

emphysema - overview

Answer 18

*irreversible enlargement of airspaces distal to terminal bronchiole, with destruction of septal walls without fibrosis
*destruction of alveolar sacs
*loss of elastic recoil and collapse of airways during exhalation
*clinical features: dyspnea, pink puffer, barrel-chested with obviously prolonged expiration
*radiologic features: hyperinflation, small heart

Question 19

emphysema - pathogenesis

Answer 19

*destruction of septal walls → enlarged airspaces
*toxic injury/inflammation/oxidative stress
*inflammatory protease-antiprotease imbalance (excessive increased proteases [neutrophilic elastase] OR decreased antiprotease [alpha1-antitrypsin])
*destruction of elastic fibers in septal walls → decreased elastic recoil necessary to push air out of lungs

Question 20

centriacinar (centrilobular) emphysema

Answer 20

*most common form associated with COPD
*proximal/central respiratory bronchiole acinar enlargement (distal alveoli are spared)
*more severe in upper lobes/apex

Question 21

panacinar (panlobular) emphysema

Answer 21

*associated with alpha1-antitrypsin deficiency
*uniform acinar enlargement (affects entire acinus, not entire lung)
*usually more severe in lower lobes

Question 22

emphysema - gross pathology

Answer 22

*LARGE ALVEOLI easily seen on cut surface
*apical blebs appear in advanced disease

Question 23

emphysema - microscopic pathology

Answer 23

*enlargement of the airspace
*loss of alveolar septa

Question 24

bronchiectasis - overview

Answer 24

*permanent DILATION of bronchi and bronchioles from inflammatory destruction of smooth muscle and elastic tissue
*persistent chronic/severe infections, tumors, cystic fibrosis can all cause
*clinical features:
-EPISODIC SYMPTOMS, precipitated by URIs
-severe, persistent cough
-expectoration of foul smelling, sometimes bloody sputum
-dyspnea
-hemoptysis
-paroxysms of cough

Question 25

bronchiectasis - “tram track sign” on CXR

Answer 25

Question 26

bronchiectasis - pathogenesis

Answer 26

*chronic obstruction or infections that result in a defect of airway clearance
*impaired clearance of secretions → necrosis of bronchi

Question 27

bronchiectasis - mophology

Answer 27

*commonly affects lower lobes
*may be localized to a single lung segment
*MARKEDLY DILATED AFFECTED AIRWAYS
-intense acute and chronic inflammation in walls
-epithelial desquamation and areas of ulceration
*NECROSIS OF BRONCHIAL/BRONCHIOLAR WALLS LEADS TO ABSCESS CAVITY