Radial organization of interstitial exchange pathway and influence of collagen in synovium

Abstract

The synovial intercellular space is the path by which water, nutrients, cytokines, and macromolecules enter and leave the joint cavity. In this study two structural factors influencing synovial permeability were quantified by morphometry (Delesse's principle) of synovial electronmicrographs (rabbit knee), namely interstitial volume fraction Vv.1 and the fraction of the interstitium obstructed by collagen fibrils. Mean Vv.1 across the full thickness was 0.66 +/- 0.03 SEM (n = 11); but Vv.1 actually varied systematically with depth normal to the surface, increasing nonlinearly from 0.40 +/- 0.04 (n = 5 joints) near the free surface to 0.92 +/- 0.02 near the subsynovial interface. Tending to offset this increase in transport space, however, the space "blocked" by collagen fibrils also increased nonlinearly with depth. Bundles of collagen fibrils occupied 13.6 +/- 2.4% of interstitial volume close to the free surface but 49 +/- 4.8% near the subsynovial surface (full-thickness average, 40.5 +/- 3.5%), with fibrils accounting for 48.6-57.1% of the bundle space. Because of the two counteracting compositional gradients, the space available for fibril-excluded transport (hydraulic flow and macromolecular diffusion) was relatively constant > 4 microns below the surface but constricted at the synovium-cavity interface. The space available to extracellular polymers was only 51-53% of tissue volume, raising their effective concentration and hence the lining's resistance to flow and ability to confine the synovial fluid.

Glycosaminoglycan concentration in synovium and other tissues of rabbit knee in relation to synovial hydraulic resistance.

“…The extrapolated intercept for C4S at zero C6S, namely 0 18 mg g-', was significantly different from zero (P = 0 03); this could indicate the presence of at least two proteoglycan species, one of which carries chiefly C4S, but it should be noted that the intercept is greatly influenced by the highest pair of values. Total chondroitin sulphate (Price et al 1995), the total chondroitin sulphate mass per millilitre of interstitium averaged 0-89 mg ml-1. The profiles for chondroitin sulphate concentration and C4S/C6S ratios across the whole joint are shown in Fig.…”

“…2). In an ultrastructural study of eleven such microdissected synovia, the thickness of the dissected tissue (12-2 + 0'9 /um; Price et al 1995) was no greater than that of synovium in situ and much less than the thickness of areolar subsynovium (83 + 6 #sm; Levick & McDonald, 1989 F. M. Price, J R. Le humidity from the opposite knee of the same animal was significantly lower, namely 72-7 + 3% (range, 69-8-84-2 %; P = 0 03, Wilcoxon test; n = 6). The latter value closely matches the dry weight of 28 % indicated by the results of Balazs & Denlinger (1985).…”

Changes in glycosaminoglycan concentration and synovial permeability at raised intra‐articular pressure in rabbit knees.

“…Taking the five animals where both control and perfused sample results were available from the same animal, the hyaluronan concentration in the perfused subsynovium was 1-04 + 0-22 times that in control subsynovium (P = 0 55, paired t test). Taking all cases, the hyaluronan concentration in control subsynovium was 0-526 + 0-105 mg g-1 (n = 5) and that in perfused subsynovium was 0-451 + 0 045 mg g-(n = 7; 14% difference not significant, P = 0 54, unpaired t test (Price et al 1995). Although the rise in Vv,int with perfusion did not achieve significance in that study upon analysis of variance (n = 5), an increase in superficial Vv,int from 0 54 (control) to 0-67 at 25 cmH2O would entail a 1-73-fold increase in superficial interstitial volume, which is similar to the full-thickness increase indicated by the collagen results (1*90-fold).…”

Interstitial pressure gradients around joints; location of chief resistance to fluid drainage from the rabbit knee

“…The increase in slope dQJdP, with pressure in the stab-perforated joints would seem to indicate that not only does the breach persist but also it gets bigger as stress increases in the membrane. Qualitatively similar behaviour occurs with a hole in a linearly elastic membrane (Burton, 1970); in the case of the synovium, the stress-strain relation may be highly non-linear due to its high collagen content (Price et al 1995 and wrinkling at low pressures (McDonald & Levick, 1988).…”

“…It is known that, when P, is raised, fluid drains slowly from the cavity through irregular gaps in the discontinuous layer of synoviocytes at the synovial surface. The gaps are on average 2-3,um wide at the fluidsynovium interface, where they form approximately one-third of the surface, and they widen with distance below the interface to -7 ,urn and 60% of the area at a depth of 5 ,urn (Levick & McDonald, 19896) and 90% of the area at a depth of 1Opm (Price et al 1995). The slowness of fluid drainage through such extensive apertures has been attributed to the hydraulic resistance of the matrix occupying the gaps.…”