Rheumatoid Arthritis Pathology
Rheumatoid arthritis pathology consists of the changes that take place in the tissues that are involved in the disease. These changes are mainly seen in the synovium which is the tissue that is covering the inner lining of the joints.
The very first change that occurs in the synovium is a increase in the number cells of the synovial lining. The first cells to increase are the mononuclear cells which are a type of white blood cells with a single round to oval nucleus. These accumulate around the blood vessels of the synovium.
A increase in the cells also leads to a increase in the other substances in the tissue. This results in the synovium becoming thick and swollen. This synovium now protrudes into the joint cavity in the form of small finger like projections called villi.
Symptoms of the disease begin to manifest when the mononuclear cells are replaced by T lymphocytes (white blood cells derived from the Thymus gland and responsible for cellular immunity).
As the disease progresses the synovium develops a characteristic picture of chronic (long standing) inflammatory arthritis. This consists of the following changes as seen under a laboratory microscope
- increase in size and number of synovial lining cells
- increased number of blood vessels in the synovium
- these vessels are more leaky and at places they develop blood clots
- increase in the fluid within the synovium (edema)
- presence of large number of white blood cells cells (mainly T cells) particularly around the blood vessels
- CD4+ subset of T cells predominate and are concentrated around the very small veins in the synovium
- CD8+ subset of T cell are also present in small numbers through out the synovium
- B cells (responsible for humoral immunity) mast cells and fibroblasts are also found
Mast cells contribute to rheumatoid arthritis pathology by release of histamine and fibroblast cells release enzymes that cause destruction of cartilage.
The various cells present in the synovium release certain substances called cytokines and chemokines that are responsible for mediating the inflammatory process that leads to destruction of bone and cartilage.
Cytokines and chemokines are of two types
- those that increase the inflammation
- interferon gamma
- interleukin 1 and 6
- tumor necrosis factor
- those that decrease the inflammation
- transforming growth factor beta
- interleukin 4
Cytokines and chemokines that increase inflammation are found in greater quantity than the ones that decrease the inflammation with in the synovial tissue in rheumatoid arthritis pathology.
T cells release certain cytokines that cause the B cells to produce more antibodies against the synovium. These antibodies result in the activation of the complement system (a group of proteins present in the blood that are activated sequentially and lead to cell destruction).
As the above chronic inflammation continues in the synovium simultaneously a acute inflammatory process begins in the fluid present in the joint called the synovial fliuid.
The synovium is responsible for the secretion of the synovial fluid and in normal conditions it produces very little fluid. As in the knee which is the largest joint of the body the normal amount of synovial fluid is about 0.5 ml.
When inflamed the synovium becomes leaky and releases large amounts of synovial fluid. This synovial fluid contains large number of neutrophils (a type of white blood cell). These cells are the main cell types found in acute inflammation. They also enhance the inflammatory process in rheumatoid arthritis pathology.
In spite of the presence of inflammatory mediators in the synovial fluid the destruction of the cartilage begins at the place where it is closest to the synovial tissue. This synovium forms a pannus or flap of tissue that gradually creeps over the whole of the cartilage. It consists of a large number of mononuclear cells, fibroblasts and blood vessels.
Cytokines cause the cells of the pannus to release a large amount destructive enzymes. They also stimulate the cells of the cartilage (chondrocytes) and bone (osteocytes) to release destructive enzymes.
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This page was last updated on 31st March 2009.
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