Concentration polarization of hyaluronan on the surface of the synovial lining of infused joints

Abstract

Hyaluronan (HA) in joints conserves the lubricating synovial fluid by making trans-synovial fluid escape almost insensitive to pressure elevation (e.g. effusions, joint flexion). This phenomenon, 'outflow buffering', was discovered during HA infusion into the rabbit knee joint cavity. It was also found that HA is partially reflected by the joint lining (molecular sieving), and that the reflected fraction R decreases as trans-synovial filtration rate Q is increased. It was postulated therefore that outflow buffering is mediated by HA reflection. Reflection creates a HA concentration polarization layer, the osmotic pressure of which opposes fluid loss. A steady-state, cross-flow ultrafiltration model was previously used to explain the outflow buffering and negative R-vs.-Q relation. However, the steady-state, cross-perfusion assumptions restricted the model's applicability for an infused, dead-end cavity or a non-infused joint during cyclical motion. We therefore developed a new, non-steady-state model which describes the time course of dead-end, partial HA ultrafiltration. The model describes the progressive build-up of a HA concentration polarization layer at the synovial surface over time. Using experimental parameter values, the model successfully accounts for the observed negative R-vs.-Q relation and shows that the HA reflected fraction (R) also depends on HA diffusivity, membrane area expansion and the synovial HA reflection coefficient. The non-steady-state model thus explains existing experimental work, and it is a key stage in understanding synovial fluid turnover in intact, moving, human joints or osteoarthritic joints treated by HA injections.

Hyaluronan molecular reflection by synovial lining is concentration dependent and reduced in dilute effusions in a rabbit model

“…In a study directed specifically at the effect of filtration rate, R lymph was a graded, negative function of filtration rate, ranging from 0.93 at 6 μl/minute to 0.14 at 89 μl/minute with 0.2 mg/ml HA (7). The higher the filtration rate, the more HA accumulates on the membrane surface, and therefore the greater the amount available locally to pass through the membrane (8). Because of this known effect of filtration rate, the HA 1.5 series and HA 0.2 series were carried out at matched filtration rates.…”

“…After an initial 30 minutes, lymph was removed from the fluid trap every 15 minutes for 2–3 hours. The lymph flow and composition are at close to a steady state over this period, within the limits of experimental error (6), though a mathematically defined steady state may take longer (8). Lymph samples were pooled for analysis because lymph flow is low at the low trans‐synovial filtration rates used in the present study.…”

“…An answer to the puzzle came with the discovery that synovium is a partial molecular ultrafilter. Synovium partially sieves out and reflects HA, while initially allowing water and smaller solutes to pass through (6–8); this is why the half‐life of HA in a joint is 14–32 hours, in contrast to 1–2 hours for water and plasma proteins (9–11). As synovial fluid drainage commences, HA is reflected and accumulates on the membrane surface.…”

“…As synovial fluid drainage commences, HA is reflected and accumulates on the membrane surface. This process is called concentration polarization (7, 8). The boosted osmotic pressure of this layer reduces the trans‐synovial filtration rate to a very low level (“outflow buffering”) (12, 13).…”

Hyaluronic acid secretion by synoviocytes alters under cyclic compressive load in contracted collagen gels

“…Generally, the viscosity of synovial fluid depends on the concentration and molecular weight of HA. HA is essential for absorbing mechanical stress in cartilage during periods of increased pressure, such as during sustained joint flexion (Coleman et al 2000;Lu et al 2004). In the synovial fluid of OA patients, both this viscosity and the high molecular weight of HA decrease (Saari et al 1993).…”