Pathology of Obstructive Lung Diseases

Question 1

What is the #1 spirometry characteristic of obstructive lung disease in spirometry and the two broad causes?

Answer 1

Decreased FEV1

Caused by:
1. Increased airflow resistance (i.e. chronic bronchitis, asthma)

2. Decreased outflow pressure (i.e. emphysema)

Question 2

What happens to the airways in emphysema? Are the proximal or distal? Is there fibrosis or not?

Answer 2

They become permanently enlarged distal to the terminal bronchioles due to destruction of walls and loss of radial traction.

There is no obvious fibrosis

Question 3

How does smoking cause emphysema?

Answer 3

Cigarette smoke -> causes oxidative stress and neutrophil / macrophage chemotaxis, with production of elastase and other damaging mediators

-> damage to alveoli due to excess proteolytic activity (not well compensated by alpha-1-antitrypsin function) as well as oxidation of A1AT

Question 4

What is a genetic disorder which can cause emphysema? What other disease process is associated with it and what tends to make it worse?

Answer 4

Alpha-1-antitrypsin deficiency
-> impaired secretion of A1AT, can lead to chronic liver disease and pulmonary emphysema with decreased activity to stop elastase from WBCs

Made worse with smoking (increase inflammation and elastase production)

Question 5

What type of emphysema does cigarette smoking start by causing and where in the lung is it most severe? What can it progress to?

Answer 5

Centrilobular emphysema (center of the secondary lobule, where the largest airways come in. This is where anthracosis and cigarette smoke accumulates most greatly)

• > most severe in upper lung fields (smoke rises)
• > can progress to panlobular emphysema

Question 6

What type of emphysema does alpha-1-antitrypsin deficiency cause and where is it most severe? Why?

Answer 6

Panlobular emphysema, most severe in the lower lobes (area of highest blood flow in the pulmonary system, brings the most WBCs which can not have their elastase neutralized)

Question 7

What is paraseptal emphysema and what causes it? Where in the lung is it most severe?

Answer 7

It is “distal acinar” emphysema -> destruction of most distal alveolar ducts and alveoli, adjacent to areas of pulmonary fibrosis

Typically occurs in upper lobes, especially subpleural areas of upper lobes.

Cause is unknown

Question 8

What is the possible complication of paraseptal emphysema?

Answer 8

Spontaneous pneumothorax

Question 9

What type of emphysema is associated with pulmonary scars?

Answer 9

Irregular emphysema -> focal and clinically insignificant

Question 10

What is it called when air dissects into connective tissue within lungs, and then moves thru mediastinum and subcutaneous tissue, even reaching face? What causes this?

Answer 10

Interstitial emphysema

Caused by trauma (i.e. tension pneumothorax) or increased intraalveolar pressure (i.e. due to ventilator)

Question 11

What does emphysema look like grossly, and what is it called when you have a pocket of enlarged air in the lung?

Answer 11

Expanded, hyperinflated lungs with enlarged airspaces and a thin, lacy network of supporting tissue

Called “bullae” when it is like a bubble / pocket

Question 12

What are the clinical features of a typical patient with emphysema (assuming it isn’t complicated with chronic bronchitis)?

Include cough, appearance, weight, and X-ray findings.

Answer 12

Cough - minimal and nonproductive (no increased mucus production)

Appearance - pink puffers - prolonged expiration & use of accessory muscles, with near normal SaO2

Weight - thin -> increased energy used for work of breathing

X-ray - overinflated lungs, depressed diaphragms, increased anteroposterior diameter (barrel chest)

Question 13

What is the definition of chronic bronchitis?

Answer 13

Presence of a persistent, productive cough without discernable cause for >3 months each year for at least 2 years in a row

Question 14

What is the usual pathogenesis of chronic bronchitis?

Answer 14

Chronic exposure to toxic inhalants, especially cigarette smoke, leads to increased mucus production, airway inflammation, and squamous metaplasia of airways
-> chronic airflow obstruction and recurrent pulmonary infections

Question 15

What histological index is diagnostic of chronic bronchitis within bronchi?

Answer 15

Increased Reid index above 50% (submucosal glands have hyperplasia’d to greater than 50% of the wall thickness between the epithelium and the cartilage)

Question 16

What other structural changes occur in chronic bronchitis?

Answer 16

1. Smooth muscle hyperplasia due to hyperreactive airways
2. Mixed inflammatory infiltrate, especially lymphocytes, associated with edema
3. Patchy squamous metaplasia and dysplasia

Question 17

What are the clinical features of chronic bronchitis?

Answer 17

1. Chronic cough with sputum production (diagnostic)
2. Eventual dyspnea and cyanosis
3. Recurrent pulmonary infections

Question 18

What are patients with chronic bronchitis called and why?

Answer 18

Blue bloaters -> cyanosis with edema

Cyanosis due to hypoxemia and hypercapnia

Edema occurs because poor ventilation leads to pulmonary vasoconstriction -> pulmonary hypertension -> cor pulmonale -> right heart failure with peripheral edema

Question 19

What is the definition of asthma?

Answer 19

Chronic pulmonary disease with intermittent episodes of at least partially reversible airflow obstruction associated with hyperreactive airways which bronchospasm in response to exposure to various agents

Question 20

What is status asthmaticus?

Answer 20

Most severe asthma subtype characterized by long interval of symptoms, unresponsive to therapy, which may be life-threatening

Question 21

What cytokines are involved in the Type I hypersensitivity response?

Answer 21

Th2 cells will release IL-4 (stimulating IgE production), IL-5 (stimulating eosinophil chemotaxis), and IL-13

Question 22

What happens in the acute phase reaction of allergic asthma?

Answer 22

Mast cells with IgE bound to their Fc receptors due to previous sensitization to the same stimulus will have their IgE’s crosslinked, causing degranulation and release of histamine, as well as production of leukotrienes (C4, D4, and E4, which induce smooth muscle contraction -> bronchospasm, increased vascular permeability, vasoconstriction, and prostaglandins)

Question 23

What happens in the late phase reaction of allergic asthma?

Answer 23

Prolonged disease process, with influx of WBCs, especially eosinophils and neutrophils

Question 24

What asthmatic reaction is associated with Aspergillus?

Answer 24

ABPA - allergic bronchopulmonary aspergillosis, a hypersensitivity reaction

Question 25

Can occupational exposures or environmental pollutants contribute to asthma? Give examples.

Answer 25

Yes - either hypersensitivity or direct toxic effects on airways

Occupational - industrial chemicals, metal dusts, organic things

Environmental - nitrogen oxides, ozone, cigarette smoke

Question 26

Can viruses cause asthma?

Answer 26

Yes, inflammatory response will do this -> RSV, influenza, parainfluenza

Question 27

What drugs cause asthma?

Answer 27

Beta-blcokers and aspirin (due to decreased prostaglandin synthesis and relative increase in leukotriene synthesis)

Question 28

Give three behavioral factors which can cause asthma?

Answer 28

1. Exercise - increased vascular perfusion + release of inflammatory mediators
2. Cold exposure - increased vascular perfusion and rewarming of airways
3. Emotional stress - vagal stimulation

Question 29

How does asthma appear grossly?

Answer 29

Distended, overaerated lungs with airways obstructors with mucous plugs

Question 30

What airway remodelling occurs in asthma in the bronchi / bronchioles?

Answer 30

From top to bottom:

1. Globlet cell metaplasia / mucous gland hyperplasia
2. Sub-basement membrane fibrosis
3. Edema of submucosa with inflammatory cell infiltrate with eosinophils, increased vascularity
4. Smooth muscle hyperplasia / hypertrophy (chronic bronchoconstriction)

Question 31

What diagnostic things of asthma are contained in the mucous plugs?

Answer 31

Curschmann spirals - mucoid swirls of epithelial cells

Charcot-Leyden crystals - needle-like structures formed by extruded and coalesced granules of eosinophils, next to eosinophils

Question 32

What is the definition of bronchiectasis?

Answer 32

Permanent airway dilatation due to recurrent infections, with necrosis

Question 33

What causes bronchiectasis and what will happen distally?

Answer 33

Decreased ciliary function (i.e. kartagener’s or cystic fibrosis) or chronic bronchitis leads to recurrent infections, which cause distal resportive atelectasis, continual loss of structural support, and permanent dilatation of airways with decreased clearance of secretions

Question 34

What does bronchiectasis look like grossly?

Answer 34

Markedly dilated peripheral airways extending out to pleura, especially in lower lobes (due to gravity)

Question 35

What will bronchiectasis look like microscopically and how does this relate to its clinical presentation?

Answer 35

Looked like mixed inflammatory infiltrate with ulceration, necrosis, and scarring of airways

Presentation -> mucoid / purulent sputum with dyspnea, fever, fatigue, and progressive respiratory insufficiency

Question 36

What is atelectasis? What is the exception to this definition?

Answer 36

Collapse of previous inflated lung tissue

Atelectasis neonatorum is when the lungs never completely expand at birth

Question 37

Describe the pathogenesis of obstructive atelectasis. What are some of the causes? How does the mediastinum shift?

Answer 37

Obstructive (resorptive) - COMPLETE obstruction of the airway - no trapping after inspiration -> remaining air is resorbed into blood stream, alveolar collapse

Causes: Bronchial secretions or exudate (asthma, chronic bronchitis, bronchiectasis which clogs airway), foreign body aspiration

Shift of mediastinum towards atelectic lung since there will be empty, unoccupied space

Question 38

Describe the pathogenesis of compression atelectasis. What are some of the causes? How does the mediastinum shift?

Answer 38

Pulmonary compression collapses the lung

Causes: Accumulation in the pleural cavity (pleural effusion, hemothorax, pneumothorax), diaphragmatic elevation (peritonitis, abscess, or critically ill post-op patients) -> leads to basal atelectasis

Mediastinum shifts AWAY from overfilled area -> emergent situation

Question 39

What is contraction atelectasis?

Answer 39

Atelectasis due to pulmonary fibrosis -> generalized atelectasis due to contracture

Question 40

What causes patchy atelectasis?

Answer 40

Loss of pulmonary surfactant -> respiratory distress syndromes

Question 41

What is the main complication of atelectasis?

Answer 41

Secondary pneumonia due to loss of ventilation (easily become infected)