Silicosis pathophysiology

Revision as of 14:05, 30 June 2015 by YazanDaaboul (talk | contribs)
Jump to navigation Jump to search

Silicosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Silicosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Silicosis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Silicosis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Silicosis pathophysiology

CDC on Silicosis pathophysiology

Silicosis pathophysiology in the news

Blogs on Silicosis pathophysiology

Directions to Hospitals Treating Silicosis

Risk calculators and risk factors for Silicosis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

Overview

The toxicity of crystalline silica results 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. Generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.

Pathophysiology

Pathogenesis

  • 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.
  • Generation of inflammatory cytokines (eg, interleukin-1 and tumor necrosis factor beta) by target cells results in cytokine networking between inflammatory cells and resident pulmonary cells, which in turn leads to inflammation and fibrosis.[1]
  • The alveolar macrophages are implicated as the major cell type in fibrogenesis[2], but other immune cells, namely neutrophils[3], T-lymphocytes, and mast cells are also involved.
  • Following the interaction between effector immune cells (such as alveolar macrophage) and target tissue (such as bronchiolar/alveolar epithelial cells, fibroblasts), the progression of the disease is poorly understand.
    • Injury to the alveolar type I epithelial cell is regarded as an early event in fibrogenesis followed by hyperplasia and hypertrophy[4] 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.
    • The initiation of proliferation in epithelial cells and fibroblasts by silica may occur following the upregulation of the early response proto-oncogenes C-FOS, C-JUN, and C-MYC.[5]
    • Increased expression of early response genes and protein products is also linked to the development of apoptosis[6][7]

Low Intensity Exposure vs. High Intensity Exposure

  • Lower intensity exposures to silica evoke reversible inflammatory changes characterized by focal aggregations of mineral-laden alveolar macrophages.[8]
  • In contrast, 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.

References

  1. Rimal B, Greenberg AK, Rom WN (2005). "Basic pathogenetic mechanisms in silicosis: current understanding". Curr Opin Pulm Med. 11 (2): 169–73. PMID 15699791.
  2. Oberdörster G (1994). ; "Macrophage-associated responses to chrysotile" Check |url= value (help). Ann Occup Hyg. 38 (4): 601–15, 421–2. PMID 7978983.
  3. Quinlan TR, BéruBé KA, Marsh JP, Janssen YM, Taishi P, Leslie KO; et al. (1995). ; "Patterns of inflammation, cell proliferation, and related gene expression in lung after inhalation of chrysotile asbestos" Check |url= value (help). Am J Pathol. 147 (3): 728–39. PMC 1870980. PMID 7677184.
  4. Lesur O, Bouhadiba T, Melloni B, Cantin A, Whitsett JA, Bégin R (1995). ; "Alterations of surfactant lipid turnover in silicosis: evidence of a role for surfactant-associated protein A (SP-A)" Check |url= value (help). Int J Exp Pathol. 76 (4): 287–98. PMC 1997178. PMID 7547443.
  5. Janssen YM, Heintz NH, Marsh JP, Borm PJ, Mossman BT (1994). ; "Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers" Check |url= value (help). Am J Respir Cell Mol Biol. 11 (5): 522–30. doi:10.1165/ajrcmb.11.5.7946382. PMID 7946382.
  6. BéruBé KA, Quinlan TR, Fung H, Magae J, Vacek P, Taatjes DJ; et al. (1996). ; "Apoptosis is observed in mesothelial cells after exposure to crocidolite asbestos" Check |url= value (help). Am J Respir Cell Mol Biol. 15 (1): 141–7. doi:10.1165/ajrcmb.15.1.8679218. PMID 8679218.
  7. Mossman BT, Churg A (1998). "Mechanisms in the pathogenesis of asbestosis and silicosis". Am J Respir Crit Care Med. 157 (5 Pt 1): 1666–80. doi:10.1164/ajrccm.157.5.9707141. PMID 9603153.
  8. Velan GM, Kumar RK, Cohen DD (1993). "Pulmonary inflammation and fibrosis following subacute inhalational exposure to silica: determinants of progression". Pathology. 25 (3): 282–90. PMID 8265248.


Template:WikiDoc Sources