Pneumothorax is air in the pleural space under pressure resulting in lung collapse.The pathophysiology of each type depends on the underlying disease/etiology. Primary spontaneous pneumothorax most commonly results from the bleb (small air-filled lesions under pleural surface) rupture allowing the air to leak into the pleural space. A subclass of primary spontaneous pneumothorax is isolated familial primary spontaneous pneumothorax which is genetically associated with folliculin gene mutation. Secondary spontaneous pneumothorax occurs subsequent to underlying lung pathology such as obstructive lung disease, cystic fibrosis, diffuse parenchymal lung disease and lung cancer. In tension pneumothorax, the underlying pathophysiology most commonly is chest trauma forming a one-way valve in the pleura whereby air enters the pleural space when the pleural pressure is negative during inspiration. Pneumothorax can also result from several interventional procedures which cause penetrating or non-penetrating injury to the pleura resutling in abrupt increase in the alveolar pressure and hence, lead to alveolar rupture forming a communication with the pleura.

The normal anatomy and physiology of thoracic cavity is as follows:

• Thoracic cavity is defined as the space inside the chest that contains the heart, lungs, and, several major blood vessels.^[1][2][3]

• On either side of the cavity, a pleural membrane covers the outside surface of the lung (visceral pleura) and also lines the inside of the chest wall (parietal pleura).
• The two layers are separated by a small amount of lubricating serous fluid known as the pleural fluid.
• The lungs are fully inflated within the cavity as the pressure inside the airways is higher than the pressure inside the pleural space.
• The inhaled air does not enter the pleural space as there is no natural connections between them as well as the pressure of gases in the blood stream is too low for them to be forced into the pleural space.
• The pleural pressure is negative with respect to atmospheric pressure during spontaneous breathing.
• Air can enter the pleural space through the following mechanisms:^[4][5][6]
  • Damage to the pleura or the chest wall
  • Damage to the lungs
  • Microorganisms in the pleural space

The pathophysiology of pneumothorax depends on the underlying disease causing it.

• The most common underlying pathology of primary spontaneous pneumothorax is an apical subpleural bleb (small air-filled lesions under the pleural surface).^[7]
• In addition, smoking causes inflammation and obstruction of the small airways, which is responsible for the increased risk of primary spontaneous pneumothorax in smokers.

• Pneumothorax due to underlying lung disease is secondary spontaneous pneumothorax.

• Tension pneumothorax develops when a disruption involves the visceral pleura, parietal pleura, or the tracheobronchial tree.^[8][9]

• The disruption occurs when a one-way valve forms, allowing air inflow into the pleural space, and prohibiting air outflow.
• The volume of this nonabsorbable intrapleural air increases with each inspiration.
• As a result, pressure rises within the affected hemithorax; ipsilateral lung collapses and causes hypoxia.
• Further pressure causes the mediastinum shift toward the contralateral side and compresses both, the contralateral lung and the vasculature entering the right atrium of the heart.
• This leads to worsening hypoxia and compromised venous return.

Following procedures commonly cause iatrogenic pneumothorax:^[10][11]

• Central cannulation^[12]
• Transthoracic needle aspiration
• Thoracocentesis
• Mechanical ventilation
• Thoracic acupuncture^[13][14]
• Transbronchial lung biopsy or transpleural intervention
• Intravenous drug abusers using neck veins
• Aggressive cardiopulmonary resuscitation

Mechanism of injury:

• Iatrogenic pneumothorax causes penetrating or non-penetrating injury to the pleura resulting in abrupt increase in the alveolar pressure, which can lead to alveolar rupture.
• Once the alveolus is ruptured, air enters the interstitial space and dissects toward either the visceral pleura or the mediastinum.
• A pneumothorax occurs when either the visceral or the mediastinal pleura ruptures that allows air to enter the pleural space.

The genetic association of familial primary sponatneous pneumothorax is as follows:^{[15][16][17][18][19][20]}

• Primary spontaneous pneumothorax can result as a mutation in the FLCN (folliculin) gene.
• This gene codes for a protein called folliculin.
• It is produced by the cells lining the alveoli of the lung.
• Folliculin is found in the connective tissue cells that allow the lungs to contract and expand while breathing.
• It plays a role in repairing the lung tissue after damage.
• Nonsense mutation in the folliculin gene results in isolated familial sponataneous primary pneumothorax.^[21]
• Altered folliculin protein can trigger the inflammatory process within the lung tissue that can alter and damage the tissue, resulting in blebs formation.

Pneumothorax is associated with the following conditions:^[22][23]

• Homocystinuria
• Marfan’s syndrome
  • For Marfan’s syndrome genetics, please click here.
• Iatrogenic buffalo chest syndrome

On gross pathology, pneumothorax has the following findings:^[24][25]

• Bullae or blebs on the pleural surface

• Pleural fibrosis

• Pleuropulmonary adhesions

• Airway inflammation

• The microscopic findings associated with pneumothorax are as follows:^[26]
  • Pleural fibrosis with mesothelial thickening and hyperplasia.
  • Lymphocytes, eosinophils, mesothelial thickening, and proliferation of the pleura.