Pathogenesis of Rheumatoid Arthritis:
Pathogenesis of rheumatoid arthritis indicates the changes in the
tissues affected by the disease. The changes particularly appear in the
synovium. Synovium is the inner lining of the joints.
Amongst these changes,
the very first to occur is an increase in the number of cells in the synovium.
And amongst these, the mononuclear cells are the first to increase. These are a
type of white blood cells having a single round or oval nucleus. They gather
around the blood vessels in the synovium.Because of the increase in the cells,
an increase in the other factors in the tissue also takes place, as a result of
which the synovium thickens and swells.
This thick synovium penetrates the
joint cavity. It looks like a small finger and is called villi.After some time,
the mononuclear cells are replaced by T lymphocytes, which are white blood
cells given out by the Thymus gland and have a major role in immunity. It is at
this stage when the symptoms of the disease are seen.With the progression of
the disease, the synovium manifests a characteristic form of chronic
inflammatory arthritis.
When seen under a laboratory microscope, it is seen
that there is an increase in the number and size of synovial lining cells at
this stage. There is also an increase in the number of leaking blood vessels in
the synovium, which develop blood clots at several places.
There is an
increased number of white blood cells, that too T cells in particular, around
these blood vessels. So also, B cells, which are responsible for humoral
immunity, mast cells and fibroblasts are found. Edema also occurs because of
the accumulation of fluid within synovium. CD4 subset of T cells is
concentrated around the tiny veins and CD8 subset is also present in a small
number across the synovium.In the pathogenesis of rheumatoid arthritis, mast
cells contribute by releasing histamine and fibroblast cells contribute by
releasing enzymes which destroy cartilage. Various cells in the synovium
release cytokines and chemokines. These are the substances which mediate the inflammatory
process and ultimately cause decomposition of bone and cartilage.
They are of
two types. One of the types increases inflammation and the other decreases it.
The former is found in greater quantity than the later during pathogenesis of
rheumatoid arthritis.Certain cytokines are released by T cells and they cause B
cells to produce more number of antibodies against synovium. These antibodies
activate the complement system. Complement system is a group of proteins in the
blood, which when activated, destroy cells.Simultaneously with the chronic
inflammation in the synovium, an acute inflammation too starts developing in
the synovial fluid, i.e. the fluid present in the joints.
The synovial fluid is
given out by synovium in very small quantities under normal conditions, whereas
during inflammation, the synovium leaks and secretes large amounts of synovial
fluid. This fluid contains neutrophils in large numbers which are mainly
responsible for acute inflammation.Cartilage destruction begins at a point, closest
to the synovium.
A flap of tissue, called pannus is developed from the synovium
which creeps slowly over the cartilage. Pannus contains mononuclear cells,
blood vessels and fibroblasts in a large number. The pannus cells are induced
by cytokines to secrete large amount of harmful enzymes. Bone cells, i.e.
osteocytes, and cartilage cells, i.e. chondrocytes, are also seen to be induced
by cytokines to release harmful enzymes in the pathogenesis of rheumatoid
arthritis.
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