Pathogenesis of pleurisy, pleural fibrosis, and mesothelial proliferation.

Systemic and pulmonary diseases that affect the pleura are usually characterised by accumulation of fluid in the pleural cavity or by fibrous healing of damaged mesothelium. Some of the reactive changes in the mesothelial cells and fibroblasts concerned in these processes may closely mimic neoplasia and must be distinguished from metastatic carcinoma and malignant mesothelioma. Before we consider the pathogenesis of these conditions it is necessary to understand the development and structure of pleura, the unique mechanism for regeneration of meso-thelium, and the factors responsible for breakdown of this mechanism and for the resulting fibrous repair. Development and structure of the pleura The pleura and other serous cavities develop from the extraembryonic coelom, which appears in the blasto-cyst as early as the second week of embryonic life. The parietal pleura is derived from the somatopleura, which also covers the amnion and lines the tro-phoblast; whereas the visceral pleura is derived from the splanchnopleura, which also surrounds the yolk sac.1 The pleural connective tissue and its highly spe-cialised mesothelial lining are thus derived entirely from mesoderm: parietal and visceral pleurae develop separately in the early embryo, preserving certain structural and functional differences in the adult. The anatomical layers of the pleura are shown dia-gramatically in the figure. The mesothelium and a thin layer of submesothelial connective tissue cover a well developed network of fibres that form the external elastic lamina. This is separated from the internal elastic lamina by the interstitial layer, which contains lymphatics and blood vessels and is continuous with the interlobular connective tissue. The internal elastic lamina is present in both parietal and visceral pleura, although in the latter it is indistinguisable from the elastic of the peripheral alveoli.2 The lymphatic flow in the adult lung is directed by valves.2 3 Subpleural lymphatic vessels, situated in the deep aspect of the interstitial layer, drain along the surface of the lung, as well as through intra-pulmonary lymphatic vessels, to the hilar lymph nodes.2 Intralobular pulmonary lymphatics drain outwards to the subpleural network.3 The anterior parietal and diaphragmatic lymphatics drain to the internal mammary chain. The posterior parietal and diaphragmatic lymphatics drain mainly to the inter-costal and paravertebral nodes, but also through the diaphragm to the retroperitoneal nodes.2 The controversy about the existence of stomata between the pleural space and lymphatics has been resolved largely by scanning electron microscopy and is reviewed by Whitaker etal.4 The existence of sub-diaphragmatic stomata, …