28 Pathology 3: Obstructive Lung Diseases

Question 1

Chronic obstructive pulmonary disease (COPD)

Answer 1

• Non-specific term
  
  • Describes patients who have chronic airflow obstruction manifested by a decrease in the forced expiratory volume
  • Measured by spirometric pulmonary function tests
• Usually accompanied by dyspnea clinically
• Characterized by the progressive development of airflow obstruction that is not fully reversible
• Includes two individual disorders: chronic bronchitis and emphysema

Question 2

Chronic obstructive pulmonary disease (COPD):
Chronic bronchitis

• Definition
• Most patients
• Mechanisms
• Genetic component

Answer 2

• Definition
  
  • A disease with chronic cough and sputum production on most days for at least three months of the year for at least two consecutive years
  • Symptoms should occur in the absence of cardiac or other pulmonary diseases
• Most patients
  
  • Cigarette smokers or work in occupations where there is significant exposure to inhaled bronchopulmonary irritants
  • More common among urban dwellers that are exposed to air pollutants
  • Associated with an increased risk of infection
• Mechanisms
  
  • Chronic irritation initiated by inhaled substances (primarily cigarette smoke and air pollutants), which cause morphologic and clinical abnormalities
  • This irritant effect is exacerbated by individual hypersensitivities to these irritants
• Genetic component
  
  • Patients with persistent mucus production are predisposed to infection
  • The cycle of infection, increased irritation, and underlying airway disease ultimately leads to chronic airway damage

Question 3

Chronic obstructive pulmonary disease (COPD):
Chronic bronchitis

• Gross examination of the lungs
• The changes that occur in the large cartilaginous airways are accompanied by…
• In the terminal bronchioles
• Small airway disease (chronic bronchiolitis)

Answer 3

• Gross examination of the lungs
  
  • Extensive mucus plugging of the air passages
  • Boggy, edematous, and erythematous bronchial mucosa containing prominent bronchial pits
    
    • Represent dilated ducts of the mucus secreting glands
• The changes that occur in the large cartilaginous airways are accompanied by…
  
  • Small airway alterations as well
• In the terminal bronchioles
  
  • Goblet cell metaplasia associated with chronic inflammation and mural fibrosis
  • Patchy mucus plugging may be seen
  • Airways are filled by macrophages containing the debris of air pollutants (e.g., cigarette smoke)
• Small airway disease (chronic bronchiolitis)
  
  • This inflammation of the bronchioles
  • Significant contributor to airflow obstruction

Question 4

Chronic obstructive pulmonary disease (COPD):
Chronic bronchitis:
Histologically

Answer 4

• Changes of chronic bronchitis reflect the chronic irritation to the airways
• The pseudo-stratified respiratory epithelium
  
  • Contains an abnormal number of goblet cells
  • Frequently displays squamous metaplasia (the replacement of respiratory epithelium by stratified squamous epithelium)
• Hyperplasia and hypertrophy of the tracheobronchial mucus glands
  
  • These glands normally contain a balanced mixture of serous and mucus cells, but in chronic bronchitis there is a shift to a disproportionate number of the mucus secreting cells
• Increased number of acute and chronic inflammatory cells within the submucosa of the airways and marked thickening of the basement membrane
• The smooth muscle may also be hypertrophic

Question 5

Chronic obstructive pulmonary disease (COPD):
Chronic bronchitis:
The Reid index

Answer 5

• Measure of the size of the mucus glands
• To calculate this index, the area occupied by the glands in the plane perpendicular to the cartilage and epithelium is expressed as a proportion of the thickness of the entire bronchial wall
• The normal value for the Reid Index is 0.4 or less
• Patients who have chronic bronchitis frequently have a Reid Index greater than 0.5

Question 6

Chronic obstructive pulmonary disease (COPD):
Emphysema

Answer 6

• A form of chronic obstructive pulmonary disease
• Manifested as abnormal permanent enlargement of the airspaces distal to the terminal bronchioles due to the destruction of alveolar walls
• It must be distinguished from overinflation or hyperinflation, which represents simple distention of the airspaces unassociated with a destructive component

Question 7

Chronic obstructive pulmonary disease (COPD):
Emphysema

• The major cause of emphysema
• This results in…
• Dominant theory used to explain the destruction of alveoli
• Catabolism of elastin
  
  • General
  • Due to…
  • The activity of this enzyme is controlled by…

Answer 7

• The major cause of emphysema
  
  • Cigarette smoking
• This results in increased influx of neutrophils into the pulmonary parenchyma
  
  • Accompanied by increased activation and release of proteases, particularly elastase
  • This creates an imbalance between proteases and protease inhibitors in the lung resulting in the destruction of the elastic tissue of the distal alveolar septa
• Dominant theory used to explain the destruction of alveoli
  
  • The “protease – antiprotease” hypothesis
• Catabolism of elastin
  
  • Balance between elastin production and elastin catabolism in the lung becomes disrupted in emphysema
  • Due to proteases (mainly elastase)
  • The activity of this enzyme is controlled by alpha1-antitrypsin, which is produced in the liver and reaches the lungs as a serum protein

Question 8

Chronic obstructive pulmonary disease (COPD):
Emphysema:
Clinical presentation of the hereditary deficiency of alpha-1 antitrypsin

Answer 8

• Diminished serum levels of alpha-1 antitrypsin
• Markedly enhanced tendency to develop emphysema
• Compounded by cigarette smoking
• Patients with alpha-1 antitrypsin deficiency who smoke develop emphysema 10 - 15 years earlier than their non-smoking counterparts

Question 9

Chronic obstructive pulmonary disease (COPD):
Emphysema

• Morphologically classified according to…
• This classification is based on…
• Emphysematous lungs on gross examination

Answer 9

• Morphologically classified according to…
  
  • The primary site of destruction in the pulmonary acinus
• This classification is based on…
  
  • Naked eye or hand lens examination of the lungs fixed in the inflated state
• Emphysematous lungs on gross examination
  
  • Usually voluminous
  • Frequently associated with a barrel chest deformity of the thoracic cavity, with extension of the lungs across the midline of the anterior mediastinum
  • Sometimes, there are large apical bullae, which represent the end stage of lung destruction
    
    • Bullae appear as large balloons filled with air without alveolar septa crisscrossing the central airspace
    • Frequently they are greater than 2 cm in diameter

Question 10

Chronic obstructive pulmonary disease (COPD):
Emphysema:
Histologically, the following forms of emphysema are recognized

Answer 10

• Centrilobular (centriacinar)
• Panlobular (panacinar)
• Localized (periseptal)
• Irregular

Question 11

Chronic obstructive pulmonary disease (COPD):
Emphysema:
Centrilobular (centriacinar) emphysema

Answer 11

• Most frequently encountered in cigarette smokers
• Has a predilection for the upper lobes
• The site of injury is the junction of the respiratory bronchiole and alveolar duct
• In the center of the pulmonary acinus one can identify cystic spaces reflecting the enlarged respiratory bronchioles
  
  • This may be accompanied by abnormal amounts of carbon pigment deposition in the surrounding connective tissue, which results from cigarette smoking or from air pollutants

Question 12

Chronic obstructive pulmonary disease (COPD):
Emphysema:
Panlobular (panacinar) emphysema

Answer 12

• The acinus is diffusely involved
• The destruction is localized to the alveolar duct
• “Cotton candy lung”
  
  • The pulmonary acinus is uniformly affected resulting in a microvascular alteration of the pulmonary parenchyma, with small cysts evenly dispersed throughout the pulmonary acinus
• Often found in patients with alpha-1 antitrypsin deficiency, although it can be seen in cigarette smokers
• In contrast to centrilobular emphysema, it has a predilection for the lower lobes

Question 13

Chronic obstructive pulmonary disease (COPD):
Emphysema:
Localized (periseptal) and irregular emphysema

• Localized (periseptal) emphysema
• Irregular emphysema

Answer 13

• Localized (periseptal) emphysema
  
  • Occurs adjacent to areas of scarring and fibrosis
  • Usually found in the most distal portions of the acinus, at the apex of the upper lobes
  • Its penultimate form is the emphysematous bulla
  • In most instances the remainder of the lung appears normal
• Irregular emphysema
  
  • Shows irregular involvement of the acinus (in contrast to periseptal emphysema where the distal portion of the acinus is primarily affected)
  • Almost invariably associated with scarring

Question 14

Chronic obstructive pulmonary disease (COPD):
Asthma

• Characterized by…
• Different types of asthma
• On gross examination
• With persistent bronchial asthma,…
• Another complication of asthma

Answer 14

• Characterized by increased reactivity of the tracheobronchial tree to various stimuli which elicit paroxysmal constriction of the smooth muscle of the bronchial airways
• Different types of asthma
  
  • Atopic, pharmacologic (aspirin sensitive), occupational, exercise-induced, etc.
• On gross examination
  
  • The lungs are distended with air
  • The segmental and subsegmental bronchi are plugged with mucus
    
    • Due to the mucus plugging of the small airways, the distal air spaces can become overdistended
• With persistent bronchial asthma,…
  
  • Colonization of the mucus plugs by fungi can also occur
  • Patients may develop a saprophytic fungal infection
• Another complication of asthma
  
  • Predisposition to develop bronchopneumonia and its sequelae

Question 15

Chronic obstructive pulmonary disease (COPD):
Asthma:
Histologically, four types of alterations are usually present

Answer 15

• Bronchial epithelial hyperplasia
  
  • Associated with goblet cell metaplasia and hypertrophy and hyperplasia of tracheobronchial glands
  • Results in thick plugs of mucus within the lumen of the bronchi associated with abundant eosinophils and Charcot-Leyden crystals (coalescence of eosinophil membrane protein crystalloids)
  • On cytologic preparations, the mucus forms Curschmann’s spirals representing inspissated mucus of tracheobronchial glands
• Thickening of the basement membrane
  
  • Result of persistent inflammation and epithelial injury associated with asthma
• Submucosal infiltrates of eosinophils and lymphocytes
• Hypertrophy and hyperplasia of the bronchial smooth muscle wall resulting from prolonged bronchoconstriction

Question 16

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis

• General
• Result of…
• Three main causes
• Can be caused by…
• Localized bronchiectasis

Answer 16

• The irreversible dilation of bronchi
• Result of destruction of the muscular and elastic components of the bronchial wall
• Three main causes
  
  • Bronchial obstruction
  • Post-inflammatory bronchial dilatation
  • Congenital abnormalities
• Can be caused by…
  
  • Physical obstruction of the airways by an aspirated foreign body
  • Endobronchial tumor
• Localized bronchiectasis
  
  • Caused by dilation of the airways distal to the site of obstruction
  • Because of the impaired mucociliary traffic across the mechanical obstruction, infection frequently results, exacerbating the area of destructive bronchiectasis

Question 17

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis:
Post-inflammatory dilatation

• General
• Causes
• Causes in the pediatric population

Answer 17

• General
  
  • Most common form of bronchiectasis
  • Severe infections of the lung parenchyma and tracheobronchial tree lead to irreversible damage in the form of airway dilatation associated with parenchymal scarring
• Causes
  
  • Most often caused by tuberculosis
  • Necrotizing bacterial infections
• Causes in the pediatric population
  
  • Pertussis
  • Adenovirus
  • Respiratory syncytial virus infections

Question 18

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis:
Congenital anomalies that play an important role in the development of bronchiectasis

• Congenital hypogammaglobulinemia and IgA deficiencies
• Cystic fibrosis
• Dyskinetic ciliary disorders
• Prototype syndrome for bronchial ectasia

Answer 18

• Congenital hypogammaglobulinemia and IgA deficiencies
  
  • Impaired ability to handle tracheobronchial infections
  • Frequently develop bronchiectasis
• Cystic fibrosis
  
  • Produce abnormal mucin have the inspissated mucin serve as an ideal culture media for bacterial colonization and infection, which leads to diffuse bronchiectasis
• Dyskinetic ciliary disorders
  
  • Impaired mucociliary clearance leads to repeated infections and ultimately bronchial ectasia
• Prototype syndrome for bronchial ectasia: Kartagener’s syndrome
  
  • Accompanied by situs inversus, sinusitis, and bronchiectasis due to a variety of structural defects in the cilia lining the respiratory mucosa

Question 19

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis

• Gross examination
• Airways in normal vs. bronchiectasis lungs
• Morphologically, there are three types of bronchiectasis
  
  • Saccular bronchiectasis
  • Cylindrical bronchiectasis
  • Varicose bronchiectasis

Answer 19

• Gross examination
  
  • Usually affects the lower lobes
  • Mucus plugging accompanied by dilatation of the airways in the tracheobronchial tree
    
    • These dilated airways may extend to the visceral pleura
• Airways in normal vs. bronchiectasis lungs
  
  • Airways stop 2 - 3 cm from the pleural surface
  • Extension of the airway directly to the pleura reflects some degree of bronchiectasis
• Morphologically, there are three types of bronchiectasis
  
  • Saccular bronchiectasis
    
    • Affects the most proximal portion of the tracheobronchial tree
    • These bronchi are severely dilated, form irregular sacs, without distal continuation of the airway (“blind loops”)
    • Consequently the distal lung appears collapsed and fibrotic
  • Cylindrical bronchiectasis
    
    • Involves the sixth to eighth bronchial branching
    • Displays a uniform moderate dilatation of the tracheobronchial tree
    • Airways have long toothpaste tubular enlargements
  • Varicose bronchiectasis
    
    • Resembles varicose veins with irregular dilatations and constrictions

Question 20

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis:
Histologically

• General
• The submucosa
• The adjacent pulmonary parenchyma
• The terminal bronchioles distal to sites of bronchiectasis
• Bronchial arteries within the submucosa of the large airways

Answer 20

• General
  
  • Shows similar changes to that described in chronic bronchitis
  • Usually mucous plugging with acute inflammation and squamous metaplasia of the bronchial epithelium
• The submucosa
  
  • Contains an intense acute inflammatory cell infiltrate, associated with overlying ulceration
  • May be fibrotic and lymphoid follicles are frequently seen
• The adjacent pulmonary parenchyma
  
  • Shows extensive scarring usually due to repeated bacterial or fungal pneumonias
• The terminal bronchioles distal to sites of bronchiectasis
  
  • May be inflamed or completely scarred and obliterated by connective tissue
• Bronchial arteries within the submucosa of the large airways
  
  • Enlarged
  • They are frequently the source of bloody sputum produced by the patients

Question 21

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis

• Pulmonary changes in patients with cystic fibrosis
• Histologically

Answer 21

• Pulmonary changes in patients with cystic fibrosis
  
  • The most serious complications of this disease
  • Stem from the viscous mucus secretions of the submucosal glands of the respiratory tree with secondary obstruction and infection of the air passages
  • Superimposed infections give rise to severe chronic bronchitis and bronchiectasis
  • In many instances, lung abscesses develop
• Histologically
  
  • The bronchi and bronchioles are distended with thick inspissated mucus
  • There is usually considerable squamous metaplasia of the bronchial lining epithelium
  • Bronchial walls contain numerous neutrophils
  • The peripheral lung shows pneumonia and focal fibrosis

Question 22

Chronic obstructive pulmonary disease (COPD):
Bronchiectasis:
Gross examination

• At birth
• After the first month of life
• After 4 months of age
• In adults

Answer 22

• At birth
  
  • The lungs are normal
• After the first month of life
  
  • Progressively severe changes develop including mucous plugging of the bronchial tree, bronchitis, and bronchopneumonia
• After 4 months of age
  
  • Mucopurulent plugging of the large and small airways becomes universal and bronchiectasis develops
  • The lungs appear overinflated and often contain scattered areas of bronchopneumonia, collapse, or fibrosis in addition to the bronchiectasis
• In adults
  
  • Pneumothorax is a common complication