synovium in healthy joints: role of synovial fluid macromolecules

Synovial fluid is not a static pool, but is continually being absorbed and replenished by the synovial lining of the joint cavity (synovium, synovial intima), which is approximately 20 ,m thick (rabbit knee) to approximately 60 pm thick (human knee). The three key elements for fluid turnover are the synovial capillary, synovial interstitium, and the lymphatic drainage system. Synovial capillaries. Normal areolar and adipose synovium have a row of capillaries 5 ,m (rabbit) to -30 ,um (man) beneath the surface, many bearing fenestrations (membranes of high permeability to water), often on the side facing the joint cavity.'3 The high capillary density, superficial location, and fenestral orientation are well adapted for synovial fluid formation and nutrient supply. Synovial fluid is formed primarily by ultrafiltration of plasma across the fenestral membranes, driven by a net imbalance in the 'Starling pressures' acting across the membrane. The Starling pressure imbalance is the pressure drop from capillary plasma to synovial interstitium, minus the difference in effective colloidal osmotic pressure (COP) across the capillary wall. Experimental studies of how capillary blood pressure, plasma COP and intra-articular pressure affect net trans-synovial flow have been reviewed elsewhere.4 The influence of intra-articular (IA) colloids, however, has only recently begun to be studied and is considered here. Although capillary ultrafiltrate is the raw material for synovial fluid formation, the synovial lining cells also actively secrete the glyosaminoglycan hyaluronan and the glycoprotein lubricin to produce the highly viscous, lubricating synovial fluid.6 Synovial interstitium. The path into the joint cavity from a capillary, and from joint cavity to a lymphatic vessel in the subsynovium, passes between the lining cells. These intercellular gaps, several ,um wide, contain a complex fibrous matrix (type I, III, and V collagen fibrils, type VI collagen microfibrils, hyaluronan, chondroitin and heparan proteoglycans, possibly keratan sulphate, fibronectin) in open contact with IA fluid. The hydraulic conductivity of the matrix is about 10-` cm4 s-1 dyn-' or less,7 8 which helps to reduce the rate of escape of IA fluid when joint pressure is increased (for example in flexion). Effect ofjoint motion and angle. Intra-articular fluid pressure (IAP) is an important factor affecting net flow across synovial interstitium: it opposes capillary filtration by increasing pericapillary interstitial pressure, and it promotes drainage from joint cavity to subsynovium. IAP is affected by movement of a joint, linking joint motion to fluid transport. Active or passive flexion of a normal joint can increase IAP to just above atmospheric pressure (much greater for effusions), whereas in extension LAP is a few cm H2O less than atmospheric. At subatmopheric pressures, net flow is often into the joint cavity, and at supra-atmospheric pressures net flow is directed out of the healthy cavity.4 5 Synovial lymphatic system. A plexus of terminal lymph vessels is found at the subsynoviumsynovium border and drains away fluid, macromolecules, and particles that have escaped from the joint cavity.6 9 10 Subsynovium comprises loose areolar tissue (substantial areas), and fatty and fibrous tissue. Areolar subsynovium connects with surrounding connective tissue planes and, like areolar tissue elsewhere, acts as a compliant, low-pressure 'sink' when fluid is driven into it, as in experiments described here.