Fibrotic lung tissue

Pathophysiology of pulmonary fibrosis

The pathophysiology of the disease is characterised by a gradual exchange of normal lung parenchyma with fibrotic tissue. This replacement with scar tissue is irreversible and decreases the oxygen diffusion capacity. With the scaring, also the compliance of the lungs severely diminishes.

Pathogenesis of pulmonary fibrosis begins with exposure to an inciting agent which may lead to the initial alveolar epithelial damage. The repair of the epithelial cell injury is dysregulated. This injury provokes the migration, proliferation, and activation of mesenchymal cells with the formation of fibroblastic foci. This results in the exaggerated accumulation of extracellular matrix with the irreversible destruction

of the lung parenchyma. Activated alveolar epithelial cells release potent cytokines and growth factors (tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ), platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), and endothelin-1 (ET-1)). These factors are involved in the migration and proliferation of fibroblasts. Fibroblasts are key effector cells in fibrogenesis, and secrete extracellular matrix proteins. Failure of apoptosis leads to fibroblast accumulation, exuberant extracellular matrix protein production, persistent tissue contraction, and pathologic scar formation. TGFβ has been shown to promote an antiapoptotic phenotype in fibroblasts.