Silicosis pathophysiology: Difference between revisions
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Both inflammation and fibrosis as well as expression of genes linked to cell proliferation and antioxidant defense occur in a dose-related fashion after inhalation exposures to asbestos (77). Lower intensity exposures to silica (78) evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar macrophages, where as, higher exposures elicit intense and protracted inflammatory changes, cell proliferation in various compartments of the lung, and excessive deposition of collagen and other extracellular matrix components by mesenchymal cells. The AM is implicated as a major cell type in fibrogenesis (reviewed in references 79 and 80). In addition, various cell types of the immune system, including neutrophils (78, 81), T-lymphocytes (29, 82), and mast cells (83, 84) are also implicated in the development of fibrosis. A multiplicity of interactions between these effector cells and “target” cell types of injury, including bronchiolar, alveolar epithelial cells and fibroblasts, may govern the pathogenesis and progression of disease. | |||
Injury to the alveolar type I epithelial cell is regarded as an early event in fibrogenesis followed by hyperplasia and hypertrophy (85) of type II epithelial cells. Silica-induced cell hyperproliferation of mesenchymal cells is also a hallmark of the fibrotic lesion. Proliferation may occur intially at sites of accumulation of inhaled minerals, but later at distal sites where particles or fibers are translocated over time. Alternatively, mitogenic cytokines may mediate signaling events, leading to cell replication at sites physically remote from fibers (89, 90). The initiation of proliferation in epithelial cells and fibroblasts by asbestos or silica may occur after upregulation of the early response protooncogenes, c-fos, c-jun, and c-myc (77, 91– 93). c-fos and c-jun encode proteins of the Fos and Jun family | |||
Increased expression of early response genes and protein products is also linked to the development of apoptosis (97, 98) | |||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
Silica (silicon dioxide) is the most abundant mineral on earth. Silica exists in crystalline and amorphous forms. Crystalline silica (quartz, cristobalite, and tridymite) is associated with a spectrum of pulmonary diseases. Amorphous forms, including vitreous silica and diatomite (formed from skeletons of prehistoric marine organisms), are relatively less toxic after inhalation [18].
Quartz is the most abundant form of crystalline silica and is a major component of rocks including granite, slate, and sandstone. Granite contains about 30 percent free silica, slate about 40 percent, and sandstone is almost pure silica [19]. Cristobalite and tridymite occur naturally in lava and are formed when quartz or amorphous silica is subjected to very high temperatures.
The toxicity of crystalline silica appears to result from the ability of crystalline silica surfaces to interact with aqueous media, to generate oxygen radicals, and to injure target pulmonary cells such as alveolar macrophages. Resultant generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells lead to cytokine networking between inflammatory cells and resident pulmonary cells, resulting in inflammation and fibrosis [20].
"Free" crystalline silica is unbound to other minerals. "Combined" forms of silica, called silicates, are compounds in which silica is bound to other minerals. Examples of silicates used in industry include asbestos (hydrated magnesium silicate), talc (Mg3Si4O10(OH)2), and kaolinite (Al2Si2O5(OH)4), a major component of kaolin (china clay) [21]. The pulmonary effects of asbestos inhalation are substantial, and are discussed separately
Both inflammation and fibrosis as well as expression of genes linked to cell proliferation and antioxidant defense occur in a dose-related fashion after inhalation exposures to asbestos (77). Lower intensity exposures to silica (78) evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar macrophages, where as, higher exposures elicit intense and protracted inflammatory changes, cell proliferation in various compartments of the lung, and excessive deposition of collagen and other extracellular matrix components by mesenchymal cells. The AM is implicated as a major cell type in fibrogenesis (reviewed in references 79 and 80). In addition, various cell types of the immune system, including neutrophils (78, 81), T-lymphocytes (29, 82), and mast cells (83, 84) are also implicated in the development of fibrosis. A multiplicity of interactions between these effector cells and “target” cell types of injury, including bronchiolar, alveolar epithelial cells and fibroblasts, may govern the pathogenesis and progression of disease.
Injury to the alveolar type I epithelial cell is regarded as an early event in fibrogenesis followed by hyperplasia and hypertrophy (85) of type II epithelial cells. Silica-induced cell hyperproliferation of mesenchymal cells is also a hallmark of the fibrotic lesion. Proliferation may occur intially at sites of accumulation of inhaled minerals, but later at distal sites where particles or fibers are translocated over time. Alternatively, mitogenic cytokines may mediate signaling events, leading to cell replication at sites physically remote from fibers (89, 90). The initiation of proliferation in epithelial cells and fibroblasts by asbestos or silica may occur after upregulation of the early response protooncogenes, c-fos, c-jun, and c-myc (77, 91– 93). c-fos and c-jun encode proteins of the Fos and Jun family Increased expression of early response genes and protein products is also linked to the development of apoptosis (97, 98)
When small silica dust particles are inhaled, they can embed themselves deeply into the tiny alveolar sacs and ducts in the lungs, where oxygen and carbon dioxide gases are exchanged. There, the lungs cannot clear out the dust by mucous or coughing.
When fine particles of silica dust are deposited in the lungs, macrophages that ingest the dust particles will set off an inflammation response by releasing tumor necrosis factors, interleukin-1, leukotriene B4 and other cytokines. In turn, these stimulate fibroblasts to proliferate and produce collagen around the silica particle, thus resulting in fibrosis and the formation of the nodular lesions.
Furthermore, the surface of silicon dust can generate silicon-based radicals that lead to the production of hydroxyl and oxygen radicals, as well as hydrogen peroxide, which can inflict damage to the surrounding cells.
Characteristic lung tissue pathology in nodular silicosis consists of fibrotic nodules with concentric "onion-skinned" arrangement of collagen fibers, central hyalinization, and a cellular peripheral zone, with lightly birefringent particles seen under polarized light. In acute silicosis, microscopic pathology shows a periodic acid-Schiff positive alveolar exudate (alveolar lipoproteinosis) and a cellular infiltrate of the alveolar walls.