Effect of extravascular plasma protein on pressure‐flow relations across synovium in anaesthetized rabbits.

Abstract

SUMMARY1. The effect of extravascular plasma protein on fluid flux through interstitial matrix was investigated in vivo by studying the pressure-flow relation across synovium during intra-articular infusions of protein solutions (usually bovine serum albumin). Synovium is a sheet of non-epithelial cells separated by interstitium-filled gaps, beneath which are fenestrated capillaries: synovium regulates synovial fluid volume and composition.2. Albumin solutions (10-150 g l-) of measured oncotic pressure and viscosity were infused at known pressure into the synovial cavity of knees of anaesthetized rabbits. Flow across the synovial lining in the steady state (absorption rate Q8) was recorded at a series of joint pressures (Ps) to define the pressure-flow relation. Krebs solution was infused into the opposite knee as a control (26 animals).3. Infusion of a low albumin concentration (10 g l-, bovine or rabbit) or diluted rabbit serum revealed no specific effect of plasma protein on interstitial matrix permeability (cf. specific protein effect on capillary glycocalyx permeability). Physiological (22-5 g l-') and higher concentrations reduced trans-synovial absorption rate. The slope of the pressure-flow relation was reduced and the pressure intercept displaced to the right (i.e. P, at zero flow was raised).4. Slope dQo/dP, correlated negatively with intra-articular viscosity (P= 0-001-0-04), in keeping with viscous interstitial flow. The reduction in normalized slope, however, did not equal the reduction in fluidity (1/viscosity) quantitatively. It is proposed that apparent fluidity within the interstitial matrix is higher than in the bulk phase due to steric exclusion of albumin (radius 3-55 nm) by the interstitial glycosaminoglycans. The latter form spaces of estimated mean hydraulic radius 14-18 nm in synovium.5. The joint-pressure intercept at zero net trans-synovial flow was displaced 0.015 cmH20 per cmH20 intra-articular oncotic pressure (nr,; S.E.M. + 0-006). Thus large trans-synovial osmotic gradients were not maintained at physiological flow velocities. The 1-5 % displacement of the P, intercept by nr, was attributed principally to interstitial albumin exerting pericapillary oncotic pressure and enhancing net Starling filtration pressure. Indeed, net trans-synovial flow at low

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

“…The shallow subsynovial gradient was in broad agreement with a previous study using a much coarser, 23-gauge steel cannula, which recorded a relatively uniform periarticular pressure of -1 cmH20 around a joint cavity inflated to 21 cmH,O (McDonald & Levick, 1993).…”

Transient transcapillary exchange of water driven by osmotic forces in the heart

“…Solution osmolarity was validated with a freezing-point osmometer for the small solutes (Osmette A, Precision Systems). For the albumin test solution the concentration, C, was measured by protein refractometry (accurate to about Ϯ0.2 g/l) and the osmolarity was calculated by the formula ϭ 0.345C ϩ 0.002657C 2 ϩ 2.26 ϫ 10 Ϫ5 C 3 from McDonald and Levick (34). The increases in osmolarity due to the additions of the test solute were (in the same order) 30,38,30,30,30,5, and 0.5 mosM.…”

A model of synovial fluid lubricant composition in normal and injured joints

“…IL-1 downregulates PRG4 secretion by chondrocytes, while TGF-β upregulates PRG4 secretion (Flannery et al, 1999;. Additionally, both TGF-β and IL-1 result in increased HA secretion by synoviocytes (Haubeck et al, 1995;Momberger et al, 2005). Thus, the changing chemical environment with injury and arthritis may have significant effects on lubricant secretion by cells, and, consequently, SF lubricant composition.…”

“…Additionally, the flux of lubricants due to fluid convection is also considered negligible compared to the flux due to diffusion, as the ratio of convective transport of solute to diffusive transport of solute was estimated for albumin to be <<1 (McDonald and Levick, 1993):…”

“…Molecules postulated to play a key role, alone or in combination, in lubrication are proteoglycan 4 (PRG4) (Swann et al, 1985) present in SF at a concentration of 0.05-0.35 mg/ml (Schmid et al, 2001a), hyaluronan (HA) (Ogston and Stanier, 1953) at 1-4 mg/ml (Mazzucco et al, 2004), and surface-active phospholipids (SAPL) (Schwarz and Hills, 1998) at 0.1 mg/ml (Mazzucco et al, 2004). Synoviocytes secrete PRG4 (Jay et al, 2000;Schumacher et al, 1999) and are the major source of SAPL (Dobbie et al, 1995;Hills and Crawford, 2003;Schwarz and Hills, 1996), as well as HA (Haubeck et al, 1995;Momberger et al, 2005), in SF. Other cells also secrete PRG4, including chondrocytes in the superficial layer of articular cartilage (Schmid et al, 2001b;Schumacher et al, 1994) and, to a much lesser extent, cells in the meniscus .…”