How is a secondary lung lobule formed in a normal lung and in individuals with underlying lung disease, such as Chronic Obstructive Pulmonary Disease (COPD) or pneumonia?

Secondary Pulmonary Lobule Structure

Normal Anatomical Composition

The secondary pulmonary lobule is the smallest functional unit of lung structure bounded by connective tissue septa, measuring 10-25mm in diameter in adults, and contains 3-5 terminal bronchioles with their associated airways, vessels, and alveoli. 1

Core Structural Components

The secondary lobule reproduces the entire lung architecture in miniature and includes the following elements 1:

• Central bronchovascular bundle: Contains a terminal bronchiole (part of the conducting airway hierarchy) and accompanying pulmonary artery branch that course together through the center of the lobule 1, 2
• Peripheral interlobular septa: Fibrous connective tissue boundaries that contain pulmonary veins and lymphatics, defining the polygonal shape of the lobule 2
• Parenchymal tissue: Multiple acini (3-5 per lobule) that represent the gas-exchanging units, each measuring 6-10mm in diameter in adults 3
• Lymphatic channels: Run within both the bronchovascular bundles and interlobular septa 2

Developmental Considerations

The secondary lobule undergoes significant postnatal growth 3:

• At birth: Mean diameter of 3mm
• By 1 year: Increases to 5mm
• By 4 years: Reaches 9mm
• By 12 years: Measures 15mm
• Adult size: 13-20mm diameter range achieved in late adolescence 3

Structural Changes in COPD

Emphysematous Destruction Patterns

In COPD, the secondary lobule undergoes characteristic pathological alterations depending on the emphysema subtype 4:

Centriacinar (centrilobular) emphysema 4:

• Destroys respiratory bronchioles, alveolar ducts, and alveoli at the center of the acinus/lobule
• Surrounding alveoli at the lobular periphery remain relatively intact initially
• Most common pattern in smokers
• Preferentially affects upper lobes

Panacinar emphysema 4:

• Involves destruction of the entire acinus uniformly
• All components from respiratory bronchioles through alveoli are affected
• Associated with alpha-1 antitrypsin deficiency
• Preferentially affects lower lobes

Paraseptal emphysema 4:

• Affects areas adjacent to the connective tissue septa (the interlobular boundaries)
• Forms subpleural blebs and bullae
• Predisposes to spontaneous pneumothorax

Small Airway Disease

The peripheral airways (small bronchi and bronchioles) within the secondary lobule are major sites of pathology in COPD 4:

• Goblet cell hyperplasia: Increased mucus-secreting cells in airways normally lacking them 4
• Intraluminal mucus accumulation: Obstructs small airways 4
• Inflammatory infiltration: Predominantly mononuclear cells in mucosa and neutrophils in airway fluid 4
• Wall thickening: Increased muscle mass and fibrosis narrow the airway lumen 4
• Loss of alveolar attachments: Bronchioles lose their structural support, leading to collapse during expiration 4
• Airway obliteration: Complete closure of small airways in advanced disease 4

Functional Consequences

These structural changes produce characteristic CT imaging findings 4:

• Centrilobular nodules: Reflect peribronchiolar inflammation within the center of the secondary lobule 4
• Mosaic attenuation: Geographic patchwork of varying lung density due to heterogeneous small airway obstruction and air trapping 4
• Loss of normal polygonal lobular architecture: Fibrosis and emphysematous destruction distort the regular septal boundaries 2

Structural Changes in Pneumonia

Lobular Consolidation Patterns

In pneumonia, the secondary lobule fills with inflammatory exudate, creating distinct radiologic patterns 5:

• Acinar nodules: Small (6-10mm) rounded opacities representing individual acini filled with exudate, though these are relatively rare on imaging 5
• Lobular consolidation: Confluent opacification of entire secondary lobules (10-25mm), more commonly seen than isolated acinar filling 5
• Peribronchial infiltration: Inflammation centered around the bronchovascular bundle can mimic acinar disease 5

Interacinar Spread

The secondary lobule is not a completely sealed unit 6:

• Interacinar ducts: Short tubular structures (~200μm diameter) connect adjacent acini, allowing disease spread between acini within and across lobular boundaries 6
• Lobular septa as barriers: The fibrous interlobular septa provide some resistance to spread, making the secondary lobule (rather than the individual acinus) the smallest functional unit of airspace disease 6
• This explains why pneumonia typically spreads in lobular rather than purely acinar patterns 6

Clinical Pitfalls

Critical distinction: The secondary lobule should not be confused with the primary lobule (synonymous with acinus), which is 3-5 times smaller 3. This distinction matters because:

• High-resolution CT can visualize secondary lobular anatomy but typically cannot resolve individual acini 1
• Disease patterns described as "centrilobular" refer to the center of the secondary lobule (where terminal bronchioles reside), not the center of individual acini 4, 1
• The interlobular septa visible on CT define secondary lobules, not acinar boundaries 2