The """"""""logic of nature"""""""" has determined that many rheumatic diseases follow characteristic patterns in distirbution of involved joints, in biochemical constituents of synovial effusions, and in selective injury to either convex or concave joint members. Although many of these patterns are diagnostically useful, little is known about their uderlying pathophysiology. The present project considers synovial effusions as microvascular disorders and employs new quantitative means to characterize the vascular physiology of normal synovium in different joints and of inflamed synovium in experimental synovitis. These new tools include assessments of 1) the effective synovial blood flow (clearance of iodide from the joint space in ml/min), 2) effective rate of lymphatic drainage from (clearance of radiolabelled albumin in ml/min), 3) the flux rate at which each protein traverses the joint space (mg/min), 4) the volume of plasma cleared of a specific protein by entry into the joint space (ml/min), 5) the filtration fraction of perfusing plasma which leaves synovial microvessels and returns to the circulation through lymphatics (%), 6) the fraction of each plasma protein which enters the joint space per passage through the microvasculature (%), and 7) the transitional microvascular pressure where filtration stops and reabsorption begins (mmHg). These new tools will be used to contrast the pathophysiology of acute and chronic experimental synovitis, and to evalute the contributions of specific Starling forces to net fluid balance of articular tissues in dogs. Concurrent studies of juxtaarticular bone will contrast the human femoral head and its opposing acetabulum using fully automated morphometry to examine trabecular structure at varying subchondral depths. Biomechanical studies of the same specimens will further test our hypothesis that convex joint members are flexible and are hydraulically supported in contrast to their stiff but elastic concave mates. Subsequent studies include tensile loading and cyclic compression of hip joints, biomechanical studies of the lumbar spine, and allometric morphometry of mammalian hips.
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