Joint Lubrication

The mechanics of joint lubrication have provided a focus of
investigation beginning with the unique structure of the bearing
surface.

Articular cartilage is elastic, fluid-filled, and backed by a relatively
impervious layer of calcified cartilage and bone. This means that load-
induced compression of cartilage will force interstitial fluid to flow
laterally within the tissue and to surface through adjacent cartilage.
As that area, in turn, becomes load bearing, it is partially protected
by the newly expressed fluid above it. This is a special form of
hydrodynamic lubrication, so-called because the dynamic motion of the
bearing areas produces an aqueous layer that separates and protects the
contact points.

Boundary layer lubrication is the second major low-friction
characteristic of normal joints. Here, the critical factor is proposed
to be a small glycoprotein called lubricin. The lubricating properties
of this synovium-derived molecule are highly specific and depend on its
ability to bind to articular cartilage where it retains a protective
layer of water molecules. Lubricin is not effective in artificial
systems and thus does not lubricate artificial joints.

     Other lubricating mechanisms have been proposed; some remain under
investigation. Interestingly, hyaluronic acid, the molecule that makes
synovial fluid viscous (synovia means "like egg white"), has largely
been excluded as a lubricant of the cartilage-on-cartilage bearing.
Instead, hyaluronate lubricates a quite different site of surface
contact-that of synovium on cartilage. The well-vascularized, well-
innervated synovium must alternately contract and then expand to cover
non-loaded cartilage surfaces as each joint moves through its normal
range of motion. This process must proceed freely. Were synovial tissue
to be pinched, there would be immediate pain, intraarticular bleeding,
and inevitable functional compromise. The rarity of these problems
testifies to the effectiveness of hyaluronate-mediated synovial
lubrication.

     SYNOVIAL FLUID

     In normal human joints, a thin film of synovial fluid covers the
surfaces of synovium and cartilage within the joint space. The volume of
this fluid increases when disease is present to provide an effusion that
is clinically apparent and may be easily aspirated for study. For this
reason, most knowledge of human synovial fluid comes from patients with
joint disease. Because of the clinical frequency, volume, and
accessibility of knee effusions, our knowledge is largely limited to
findings in that joint.

     In the synovium, as in all tissues, essential nutrients are
delivered and metabolic by-products are cleared by the bloodstream
perfusing the local vasculature. Synovial microvessels contain
fenestrations that facilitate diffusion-based exchange between plasma
and the surrounding interstitium. Free diffusion provides full
equilibration of small solutes between plasma and the immediate
interstitial space. Further diffusion extends this equilibration process
to include all other intracapsular spaces including the synovial fluid
and the interstitial fluid of cartilage. Synovial plasma flow and the
narrow diffusion path between synovial lining cells provide the
principal limitations on exchange rates between plasma and synovial
fluid.

     This process is clinically relevant to the transport of therapeutic
agents in inflamed synovial joints. Many investigators have made serial
observations of drug concentrations in plasma and synovial fluid after
oral or intravenous administration. Predictably, plasma levels exceed
those in synovial fluid during the early phases of absorption and
distribution. This gradient reverses during the subsequent period of
elimination when intrasynovial levels exceed those of plasma. These
patterns reflect passive diffusion alone, and no therapeutic agent is
known to be transported into or selectively retained within the joint
space.

     Metabolic evidence of ischemia provides a second instance when the
delivery and removal of small solutes becomes clinically relevant. In
normal joints and in most pathologic effusions, essentially full
equilibration exists between plasma and synovial fluid. The gradients
that drive net delivery of nutrients (glucose and oxygen) or removal of
wastes (lactate and carbon dioxide) are too small to be detected. In
some cases, however, the synovial microvascular supply is unable to meet
local metabolic demand, and significant gradients develop. In these
joints, the synovial fluid reveals a low oxygen pressure (PO2), low
glucose, low pH, high lactate, and high carbon dioxide pressure (PCO2).
Such fluids are found regularly in septic arthritis, often in rheumatoid
disease, and infrequently in other kinds of synovitis. Such findings
presumably reflect both the increased metabolic demand of hyperplastic
tissue and impaired microvascular supply.

     Consistent with this interpretation is the finding that ischemic
rheumatoid joints are colder than joints containing synovial fluid in
full equilibration with plasma. Like other peripheral tissues, joints
normally have temperatures lower than that of the body's core. The knee,
for instance, has a normal intraarticular temperature of 32¡C. With
acute local inflammation, articular blood flow increases and the
temperature approaches 37¡C. As rheumatoid synovitis persists, however,
microcirculatory compromise may cause the temperature to fall as the
tissues become ischemic.

     The clinical implications of local ischemia remain under
investigation. Decreased synovial fluid pH, for instance, was found to
correlate strongly with radiographic evidence of joint damage in
rheumatoid knees. Other work has shown that either joint flexion or
quadriceps contraction may increase intrasynovial pressure and thereby
exert a tamponade effect on the synovial vasculature. This finding
suggests that normal use of swollen joints may create a cycle of
ischemia and reperfusion that leads to tissue damage by toxic oxygen
radicals.

     Normal articular cartilage has no microvascular supply of its own
and, therefore, is at risk in ischemic joints. In this tissue, the
normal process of diffusion is supplemented by the convection induced by
cyclic compression and release during joint usage. In immature joints,
the same pumping process promotes exchange of small molecules with the
interstitial fluid of underlying trabecular bone. In adults, however,
this potential route of supply is considered unlikely, and all exchange
of solutes may occur through synovial fluid. This means that normal
chondrocytes are farther from their supporting microvasculature than are
any other cells in the body. The vulnerability of this extended supply
line is clearly shown in synovial ischemia.

     The normal proteins of plasma also enter synovial fluid by passive
diffusion. In contrast to small molecules, however, protein
concentrations remain substantially less in synovial fluid than in
plasma. In aspirates from normal knees, the total protein was only 1.3
g/dL, a value roughly 20% of that in normal plasma. Moreover, the
distribution of intrasynovial proteins differs from that found in
plasma. Large proteins such as IgM and cr2-macroglobulin are
underrepresented, whereas smaller proteins are present in relatively
higher concentrations. The mechanism determining this pattern is
reasonably well understood. The microvascular endothelium provides the
major barrier limiting the escape of plasma proteins into the
surrounding synovial interstitium. The protein path across the
endothelium is not yet clear; conflicting experimental evidence supports
the fenestrae, intercellular junctions, and cytoplasmic vesicles as the
predominant sites of plasma protein escape. What does seem clear is that
the process follows diffusion kinetics. This means that smaller
proteins, which have fast diffusion coefficients, will enter the joint
space at rates proportionately faster than those of large proteins with
relatively slow diffusion coefficients.

     In contrast, proteins leave synovial fluid through Iymphatic
vessels, a process that is not size-selective. Protein clearance may
vary with joint disease. In particular, joints affected by rheumatoid
arthritis (RA) experience significantly more rapid removal of proteins
than do those of patients with osteoarthritis. Thus, in all joints,
there is a continuing, passive transport of plasma proteins involving
synovial delivery in the microvasculature, diffusion across the
endothelium, and ultimate Iymphatic return to plasma.

     The intrasynovial concentration of any protein represents the net
contributions of plasma concentration, synovial blood flow,
microvascular permeability, and Iymphatic removal. Specific proteins may
be produced or consumed within the joint space. Thus, lubricin is
normally synthesized within synovial cells and released into synovial
fluid where it facilitates boundary layer lubrication of the cartilage-
on-cartilage bearing. In disease, additional proteins may be
synthesized, such as IgG rheumatoid factor in RA, or released by
inflammatory cells, such as Iysosomal enzymes. In contrast,
intraarticular proteins may be depleted by local consumption, as are
complement components in rheumatoid disease.

     Synovial fluid protein concentrations vary little between highly
inflamed rheumatoid joints and modestly involved osteoarthritic
articulations. Microvascular permeability to protein, however, is more
than twice as great in RA as in osteoarthritis. This marked difference
in permeability leads to only a minimal increase in protein
concentration, because the enhanced ingress of proteins is largely
offset by a comparable rise in Iymphatic egress. These findings
illustrate that synovial microvascular permeability cannot be evaluated
from protein concentrations unless the kinetics of delivery or removal
are concurrently assessed.

     Adapted from a section in the Primer on the Rheumatic Diseases 10th
edition by Peter A. Simkin, MD. This material is protected by copyright.

From here you can return to the beginning.
Introduction... Joint Lubrication

Edited by: Frederick Matsen III MD Chairman,
Department of Orthopaedics,
University of Washington, Seattle, USA