Lecture 32 Chronic Obstructive Pulmonary Disease

Pathology

Lecture 32 Chronic Obstructive Pulmonary Disease

1) List the various types of chronic diseases characterized by airflow obstruction and define chronic obstructive pulmonary disease (COPD).

1) Emphysema, 2) Chronic Bronchitis with Bronchiolitis (Small Airways Disease), 3) Asthma, 4) Bronchiectasis

Chronic Obstructive Pulmonary Disease (COPD) - a clinical syndrome characterized by chronic airflow limitation from a mixture of emphysema and airways disease, excluding asthma and other clearly definable conditions. Caused primarily by smoking.

2) Define atelectasis, emphysema, hyperinflation, interstitial emphysema, and pneumothorax.

Atelectasis - a condition of alveolar collapse and which are is not present in alveoli.

Emphysema - a condition of the lung characterized by abnormal, permanent enlargement of the airspaces distal to the terminal bronchial, accompanied by destruction of their walls, without obvious fibrosis.

Hyperinflation - alveolar inflation that is at or near total lung capacity.

Interstitial emphysema - air in the fibrous framework of the lung.

Pneumothorax - air in the pleural space at atmospheric pressure or greater (tension pneumothorax).

3) Characterize the two most common types of emphysema in terms of their gross appearance, microscopic appearance, location in the acinus, association with smoking, and association with α-1-antitrypsin (α-1-AT) deficiency.

4) Explain the protease-antiprotease theory of emphysema, especially how persons without α-1-AT deficiency can get emphysema. α-1-antitrypsin is the major human anti-protease (enzyme that destroys endogenously released proteases). α-1-AT deficiency results in panacinar emphysema presenting in early adulthood. α-1-AT neutralizes elastase released by inflammatory cells, especially neutrophils, and elastin is the important skeletal component of the lungs. Emphysema results from the imbalance of proteinase (neutrophil elastase) and anti-proteinase (α-1-AT). Additionally, smokers have more neutrophils in their lungs and smoke directly inhibits α-1-AT.

5) Outline the clinical manifestations and clinical course of patients with COPD. Nonspecific symptoms: sometimes cough, sometimes sputum production, typically shortness of breath; most characteristic is slowing of forced expiration. Patients can be "blue bloaters" or "pink puffers" but most are somewhere in between.

Blue bloaters - generally younger patients with predominantly small airways disease. They have peripheral cyanosis and may develop cor pulmonale more readily.

Pink puffers - generally older patients with predominantly emphysema. They have a ruddy complexion because of secondary polycythemia (increased red blood cell mass). They appear to have larger lungs and may not develop cor pulmonale.

6) Contrast how small airways disease produces expiratory airflow limitation, compared with emphysema. Small airways disease involves noncartillagenous, nonalveolated airways in the range of 2-0.3 mm. Forced expiration is limited due to changes in the bronchioles including fibrosis, inflammation, muscular hypertrophy, pigment accumulation, mucous plugging, and epithelial abnormalities. Clinically, small airways disease is extremely difficult to separate from emphysema. In emphysema, expiratory airflow limitation is caused by a loss in lung recoil due to destruction of elastin in alveolar walls.

7) Explain the difference between simple chronic bronchitis and obstructive chronic bronchitis. In simple chronic bronchitis, patients have a productive cough, but no physiologic evidence of airflow obstruction. Patients are more prone to infective bronchitis. In obstructive chronic bronchitis, there is airflow obstruction with evidence of associated emphysema.

8) Define asthma. Asthma is a chronic inflammatory disease characterized by hyperreactive airways (increased responsiveness to various stimuli) leading to episodic, usually reversible bronchoconstriction. Asthma is generally associated with atopy, the tendency to generate excess IgE in response to external allergens.

9) Explain the mechanisms for the immediate and late phase reaction in asthma.

Immediate phase: initiated by type I hypersensitivity reaction, IgE-coated mast cells bind allergen, released leukotriene's, histamine, acetylcholine, etc.; IL-5 attracts eosinophils.

Late phase: mediated by leukocytes (recruiting eosinophils) recruited by the chemotactic factors cytokines during the acute phase response. The major basic protein from eosinophils damages epithelium, causes bronchoconstriction.

10) List the three most characteristic histopathologic findings in asthma.

1. Basement membrane thickening (really collagen deposited beneath the basement membrane) is most diagnostic feature.
2. Eosinophilic infiltrates a bronchial walls.
3. Mucous plugs in airways.
4. Variable smooth muscle enlargement, bronchial gland enlargement, and chronic inflammation.