What is emphysema?

Emphysema

Emphysema is defined anatomically as a permanent destructive enlargement of airspaces distal to the terminal bronchioles, without obvious fibrosis, leading to loss of lung recoil and progressive airflow limitation. 1

Pathological Features

• Emphysema involves destruction of lung parenchyma, specifically the walls of the alveoli, leading to abnormally enlarged air spaces and reduced surface area for gas exchange 1
• The destruction is permanent and characterized by loss of alveolar wall surface area per unit volume of lung, which can be detected microscopically even before macroscopic changes are visible 1
• Loss of alveolar attachments to bronchioles occurs, contributing to airway collapse during expiration 1
• The pathological changes result in loss of lung elastic recoil, which is a key factor in airflow limitation, especially in severe COPD 1

Types of Emphysema

• Centriacinar (Centrilobular) Emphysema: Affects respiratory bronchioles, alveolar ducts, and alveoli at the center of the acinus, while surrounding alveoli remain intact; most commonly associated with cigarette smoking 1, 2
• Panacinar Emphysema: Involves destruction of the entire acinus uniformly; commonly associated with alpha-1 antitrypsin deficiency 1, 2
• Paraseptal Emphysema: Affects areas adjacent to the connective tissue septa; often leads to blebs on the lung surface which predispose to pneumothorax or giant bullae 1

Pathophysiological Consequences

• Emphysema results in loss of lung recoil, which may appear early in the development of panacinar emphysema 1
• The decreased elastic recoil leads to increased lung compliance and air trapping 1, 3
• At any pleural pressure, the lung volume is higher than normal, contributing to hyperinflation 3
• The altered relationship between pleural and alveolar pressure facilitates expiratory dynamic compression of airways, limiting airflow during forced expiration 3
• As emphysema progresses, lung elastic recoil and transfer of carbon monoxide per liter of alveolar volume (KCO) decrease, while static lung compliance and total lung capacity increase 1

Functional Consequences

• Ventilation/perfusion (V'/Q') inequality is the major mechanism impairing gas exchange and leading to arterial hypoxemia in all stages of COPD 1
• High V'/Q' units represent emphysematous regions with alveolar destruction and loss of pulmonary vasculature 1
• In advanced disease, expiration becomes flow-limited during tidal breathing, initially during exercise and later at rest 1
• The increase in functional residual capacity (FRC) is due to both static factors (loss of lung elastic recoil) and dynamic factors at the end of expiration 1
• Patients with relatively pure emphysema often maintain blood gases in or near the normal range until very late in their course 3

Associated Changes

• In advanced COPD with emphysema, changes occur in the pulmonary circulation, right heart, and respiratory muscles 1
• Loss of the vascular bed occurs as a consequence of emphysema 1
• Right ventricular enlargement due to dilatation and/or hypertrophy is not uncommon in advanced disease 1
• Atrophy of the diaphragm may occur in some cases 1

Pathogenesis

• The pathogenesis involves several mechanisms:
  • Protease-antiprotease imbalance leading to destruction of lung tissue 4, 5
  • Increased oxidative stress enhancing inflammatory response 5
  • Cellular processes including apoptosis and failed lung tissue repair 6
  • Chronic inflammation with infiltration of CD8+ T lymphocytes, neutrophils, and macrophages 5

Clinical Significance

• Emphysema is a major component of COPD and contributes significantly to airflow limitation 7
• Recognition of emphysema patterns on imaging is important for risk stratification and management planning 2
• Emphysema is associated with dyspnea, reduced exercise capacity, and relevant clinical outcomes 4
• Current pharmacological treatments have less favorable effects in emphysematous than in non-emphysematous COPD patients 4