Abstract
We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 μm, diameter < 0.25 μm) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric hindrance and by fibers motion pattern at low Reynolds numbers; it is hindered by fibrosis that increases interstitial flow resistances.
Highlights
Asbestos fibers are known to be durable and not digested or dissolved after being inhaled into the lung
The aim of this paper is that of discussing the translocation of inhaled asbestos fibers from the lung to other body compartments based on knowledge of pulmonary and pleuro-pulmonary interstitial fluid dynamics [4,5,6]
We address this issue by considering the pressure gradients governing the inter-compartmental fluid exchanges, the physical features of the corresponding flows and the particular motion pattern of anisodiametric particles dragged by such flows in the tissues and across membranes delimiting the compartments
Summary
Asbestos fibers are known to be durable and not digested or dissolved after being inhaled into the lung. The increased parenchymal stresses, that act as a "tissue safety factor" against further filtration, entailed: 1) fragmentation of chondroitin and heparansulphate proteoglycans (belonging to matrix and basement membrane, respectively) due to loosening of non-covalent bonds and activation of tissue MMPs [25]; 2) increased expression of pro-inflammatory cytokines [26], 3) signalling-transduction in lung cells (mostly endothelial) in the process of matrix remodelling and deposition [27,28,29,30] Another important consequence of the increase in interstitial pressure is the reversal of the trans-endothelial and trans-mesothelial pressure gradients allowing reabsorption of edema fluid. As discussed above, this occurs if the degree of inflammation raises lung interstitial pressure up to ~5 cm H2O. The long biopersistence in the lung can be attributed to fiber translocation by two routes, from the alveoli and from the blood; the development of fibrosis may result in a progressive greater hindrance to fiber translocation due to increased flow resistance of the porous interstitial matrix
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