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EXPERIMENTAL ARTHRITIS The Reactions of Joints to Mild Irritants
J. ALBERT KEY
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The Shriners' Hospital, St. Louis, The Department of Surgery of Washington University, St. Louis, and the Department of Anatomy of Johns Hopkins University, Baltimore.
The Journal of Bone & Joint Surgery.  1929; 11:705-738 
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Abstract

An injection of citrated blood into a normal joint caused the production of a cellular exudate which gradually disappeared in about twelve days. During the first two days after the injection, the majority of the nucleated cells in the exudates were leucocytes; but after this time their number diminished rapidly and most of the cells in the exudates were macrophages and an unusually large percentage of these were clasmatocytes.

The exudates caused by seven injections of blood were similar to the above, but the macrophages were larger and more numerous.

In the exudates caused by India ink, both the leucocytes and the macrophages remained in the joint throughout the twelve-day period and the majority of the macrophages were monocytes. In none of the joints did the synovial-lining cells exhibit any tendency to be shed off into the joint cavity.

The primitive cells resembled lymphocytes and all transitions between these cells and monocytes were seen in exudates. As collections of small round cells were seen in the subsynovial tissues it is believed that the monocytes in the exudates were largely derived from these primitive cells which multiplied in the adjacent tissues. Since showers of primitive cells were present in some of the exudates which were due to injections of blood, it is regarded as probable that the clasmatocytes were also derived from these cells.

The red blood cells were phagocytized only by clasmatocytes and apparently most of them left the joint cavity by filtering through the loose areas of the synovial surface. A few were carried out by clasmatocytes and some were entangled in fibrin clots which became adherent to the synovial surface and were organized and covered by synovial-lining cells and thus excluded from the joint cavity.

The India ink was phagocytized by leucocytes and macrophages and most of it was carried out of the joint cavity by the macrophages. A small amount of the finely divided carbon filtered through the loose areas of the synovial surface and a small amount was taken up by the synovial lining cells. Some of the ink was entangled in fibrin clots and these were exeluded from the joint by organization just as were the blood clots.

A single injection of blood caused a mild proliferation of the synovial lining cells and infiltration of the subsynovial tissues with leucocytes and macrophages, but the tissues returned to normal in about six days.

After repeated injections of blood the synovial membrane was markedly thickened. The synovial lining cells were increased in size and number, but the thickening was largely due to the proliferation of the connective-tissue cells in the loose subsynovial tissues and to the infiltration of these areas with macrophages and leucocytes. The proliferation of the surface cells and subsynovial tissues varied inversely with the density of the tissue forming the synovial surface, and in the loose areas of the joint resulted in the formation of large villi.

On the third day after the last injection the leucocytes had largely disappeared from the joint tissues, but the macrophages remained throughout the duration of the experiment. In the eleven-day and twelve-day joints there was a gradual reversion of the tissues to a condition approaching the normal, but the hyperplasia persisted for a much longer time than the experiment lasted.

The injection of India ink into joints caused a proliferation of the surface cells and subsynovial tissues which continued to progress throughout the twelve-day period. The changes were limited to the loose areas of the joint surface, and the tissues were infiltrated with leucocytes and macrophages throughout the twelve-day period. The macrophages were engorged with carbon and tended to collect in nodules or layers next to the fibrous capsule, where they degenerated and left the carbon free in the tissues.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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