Hypoxia, oxidative stress and rheumatoid arthritis.

The synovial cavity has a negative pressure in health. When the joint is exercised, vascular patency is maintained, allowing for nutrition of the avascular cartilage. In rheumatoid synovitis, the situation is altered. The cavity pressure is raised and upon movement this pressure exceeds the capillary perfusion pressure, causing collapse of the blood vessels. This leads to the production of multiple episodes of 'hypoxic-reperfusion injury' generating reactive oxygen species (ROS). Such ROS oxidise: (a) IgG, inducing rheumatoid factor production (b) Hyaluronan, leading to hyaluronan fragmentation products which may alter immune function (c) Lipids, generating aldehydes which are toxic and may alter T cell/macrophage interactions (d) lipoproteins, leading to the production of monocyte chemotactic peptides Progressive hypoxia alters immune function, predominantly by calcium mediated pathways.