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• W2124576499 abstract "It is to be expected that the extensive researches of Professor Levick and his group on the exchange of water and solutes between synovial fluid and the microcirculation of the synovial lining will advance understanding of the nutrition and lubrication of the synovial joint and of the ways in which disturbances in these processes are involved in joint disease. What is less expected is the way in which this work has raised, and often definitively answered, questions that are pertinent to many other areas of physiology and biophysics. The group has shown that transport is regulated by three barriers in series: the capillary wall, the synovial interstitium and the tissue-fluid interface. Following a detailed analysis of the structure, organisation and permeability of the fenestrated capillaries (summarised in Levick, 1995), the group was one of the earliest to recognise that the extracellular matrix is an important determinant of microvascular exchange. The relationship of the permeability properties of this extracellular matrix to its composition and organisation has been analysed in a degree of detail that has not been achieved in other tissues (reviewed in Levick et al. 1996). The data have stimulated detailed and widely applicable theoretical analysis of intersititial transport (references in Levick et al. 1996). The present paper by Coleman et al. in this issue of The Journal of Physiology relates to the third component of the resistance, the tissue-fluid interface. The high molecular weight glycosaminoglycan hyaluronan is present in synovial fluid at sufficient concentration significantly to enhance the viscosity of the fluid and this is believed to be important in joint lubrication. Levick speculated almost 20 years ago that hyaluronan should, through its effect on viscosity, impede fluid flow from the joint cavity (Levick, 1983). The first experimental test some years later demonstrated an effect, but also showed that it was not related to viscosity (McDonald & Levick, 1994). A series of investigations on the effects of pressure and solute concentration and properties, culminating in the present work, has been required to establish a mechanism. Hyaluronan, convected with the fluid expressed from the joint space, is partially reflected at the surface of the synovial lining and the accumulation of hyaluronan at the interface is partially dissipated by diffusion back into the joint space. The concentration distribution of hyaluronan close to the interface depends on the balance of molecular diffusion, hydrodynamic drag on the molecules and certain inter- and intra-molecular interactions. The three parameters are obviously not independent and are related to molecular conformation, flexibility and charge structure. Because of a lack of experimental data and a degree of mathematical intractability, understanding of the phenomenon at the molecular level is poor. Though it is a familiar problem in the engineering literature, we are not aware of any more complete solution than that offered by Coleman et al. (1999). Qualitatively, however, one would expect that shorter hyaluronan chains are likely to both pass more readily into the synovial lining and diffuse more rapidly back into the joint space. Either process would reduce the effect of the smaller hyaluronan molecules as observed in the present work. Due to the labile nature of the interfacial layer it has not proved possible to observe it directly in the synovial joint. Instead, its presence and properties are inferred from its effects on water flux. This exposes another theoretical problem: the hyaluronan layer will affect flow by a number of mechanisms. In addition to viscous drag on the polymer chains the hyaluronan network will alter the balance of osmotic forces in the system. Furthermore, if some of the molecules actually penetrate the synovial interstitium they may alter the characteristics of flow within the matrix. The distinction between surface and bulk effects may be important in explaining a qualitative difference in the effects of high and low molecular weight hyaluronan observed in the present study. The high molecular weight fractions caused the rate of fluid drainage from the joint to become independent of pressure, but the smaller molecules did not, although they significantly reduced flux at any particular pressure. The former behaviour is expected, in steady state, of a concentration polarisation layer as a result of the balance of convective transport to the boundary and diffusive flux away from it. A definitive explanation of the latter must await further experiments and the development of more elaborate theoretical models. Coleman et al. (2000) suggest that the effect of high molecular weight hyaluronan in abolishing the pressure dependence of flow, ‘flow buffering’, is physiologically important. The volume of synovial fluid in the healthy joint is remarkably small in relation to the rate of fluid transport across the joint. This design is presumably required to meet the nutritional role of the synovial fluid but it introduces the danger that a slight increase in intra-articular pressure, as may occur during flexion, would drain off all the synovial fluid. However, in the presence of hyaluronan the increase in pressure would be accompanied by an increase in outflow resistance that would reduce the risk of excessive fluid loss. In a condition such as rheumatoid arthritis, in which there is a reduction in the chain length of the hyaluronan, this protection would be lost. We anticipate that understanding of these phenomena at the molecular level will provide a stern challenge to the biophysicists. There are indications, however, that the results will be applicable to many areas of physiology (see for example Wang et al. 1999)." @default.
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• W2124576499 date "2000-07-01" @default.
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• W2124576499 title "The synovial lining: a paradigm for connective tissue research?" @default.
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• W2124576499 doi "https://doi.org/10.1111/j.1469-7793.2000.00219.x" @default.
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