Page 376 - Concise Pathology for Exam Preparation ( PDFDrive )

13 The Lung 361

• a-1 AT is synthesized in liver and is present in serum, tissue fluid and macro-
phages.
• Normal a-1 AT phenotype is PiMM.
• a-1 AT deficient phenotype is PiZZ.
• Eighty percent PiZZ patients end up with emphysema.
• Pi null phenotype has no detectable levels of a1 AT.
• Role of neutrophils: Neutrophils are a source of:
• Elastase activity
• Cellular proteases (proteinase 3 and cathepsin)
• Matrix metalloproteinases
• Oxygen-derived free radicals (inactivate native antiproteases by oxidative injury)
• Role of smoking: Smoking enhances elastase activity of macrophages. Macrophage elastase
is not inhibited by a-1 AT and it can, in fact, digest the latter.

Clinical Features of Emphysema
Patients do not become symptomatic until at least one-third of functional parenchyma is
damaged. Presenting signs and symptoms of emphysema include
• Dyspnoea
• Cough (late and with scanty sputum)
• Severe weight loss
• Barrel-shaped chest
• Prolonged expiration (key to diagnosis)
• Hunched position and breathing through pursed lips
• Death may be due to either of the following:
• Respiratory acidosis and coma
• Right-sided heart failure
• Massive collapse of lungs secondary to pneumothorax

Chronic Bronchitis
Definition
Persistent cough with sputum production for at least three months in two consecutive
years. It is common in habitual smokers and inhabitants of smoke-laden cities and
may progress to
• COPD
• Cor pulmonale and heart failure
• Atypical metaplasia and dysplasia of respiratory epithelium

Types
1. Simple chronic bronchitis: Productive cough but no physiologic evidence of airflow
obstruction
2. Chronic asthmatic bronchitis: Hyperactive airways with intermittent bronchospasm
and wheezing
3. Obstructive chronic bronchitis: Some patients, eg, heavy smokers, develop chronic
airflow obstruction usually with associated emphysema

Pathogenesis (Flowchart 13.4)

Chronic irritation (eg, tobacco smoke and pollutants) Proteases, eg, neutrophil elastase,
cathepsin and matrix metalloproteinases
Superimposed bacterial Histamine and IL-13
and viral infections
Hypersecretion of mucous and hyperplasia of submucosal glands
FLOWCHART 13.4. Pathogenesis of chronic bronchitis.

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