Factors Involved In The Disease Process:
Rheumatoid Arthritis can attack any synovial joint in the body. Early in the course of the disease several changes in
joint structures occur. Joint effusion and inflammation of the synovium occur,producing a soft tissue swelling that is easily
detected during evaluation of the patient. Additionally,changes (osteoporosis) in the ends of the bones may be present early
in the disease process.
A synovial joint has the following components:
1) A joint capsule that isolates the joint from surrounding tissue.
2) A joint cavity formed by the surrounding joint capsule.
3) A synovial membrane (synovium) that is the inner linning of the joint capsule
4) Synovial fluid that is secreated by the synovium and serves as a lubricant and carries nutrients for the joint.
5) Bones that come together to form the joint.
6) Hyaline (articular) cartilage covers and protects the ends of the bones that participate in the joint.
There will be other structures present or near the joint such as disks,cartilage (menisci),tendons,and ligaments.
Important characteristics Of these structures to remember are:
1) The joint capsule is composed of two layers,an outer fibrous layer and the inner synovium. The outer layer has many
joint receptors innervating it,but is not well vascularized. The opposite is true with the synovium. i.e.,it is well vascularized
but poorily innervated.
2) The articular cartilage has two important functions including the ability to minimize friction and wear between two
opposing joint surfaces during movement and to dissipate forces on the joint over a wider area,thus decreasing stresses on
the contacting joint surfaces.
3)Synovial fluid contains hyaluronate (hyaluronic acid) and a glycoprotein called lubricin. Both are responsible for
the lubrication of the joint,although they are specific for certain components. Hyaluronic acid is important for the lubrication
of the joint capsule while lubricin is necessary for cartilage on cartilage lubrication.
4)Synovial fluid is also the median by which nutrients are carried to,and wastes are carried from,the avascular components
of the joint.
5)The ends of the long bones that form the synovial joints are composed of a soft,spongy type of bone called subchondral
Hyaline (articular) cartilage covers this bone and protects it. Except for the very ends of the bone,long bones are usually
The attack on a joint by the disease usually occurs begins with the synovium. Early in the disease,edema begins to be
seen in the cells in the synovium and mutiplication of synovial lining cells occur.
As the disease progresses,the synovium may grow considerably larger,(thicker) eventually forming tissue called pannus.
Pannus can be considered the most destructive element affecting joints in the patients with RA. Pannus can attack articular
cartilage and destroy it. Further,pannus can destroy the soft subcondral bone once the protective articular cartilage is gone.
The synovial fluid secreted by the synovium is thought to serve two main purposes,lubrication of the joint,and provision
of nutrients to the avascular articular cartilage. In this disease process,an interaction between antibodies and antigens
occurs,and causes alterations in the composition of the synovial fluid.
Ultimately,digestants are (such as cytokines) formed in the fluid which attack the surrounding tissue. Once the composition
of this fluid is altered, it is less able to perform the normal functions,and more likely to become destructive.
The changes in the synovium and synovial fluid are responsible for a large amount of joint and soft tissue destruction.
The destruction of bone eventually leads to laxity in tendons and ligaments.
Under the strain of daily activities and other forces,these alterations in bone and joint structure result in the deformities
frequently seen in patients with RA. Considerable destruction of the joint can occur with pannus invading the subchondral
Bone destruction occurs at areas where the hyaline cartilage and the synovial lining do not adequately cover the bone.
If the disease progresses to a more advanced stage,the articular cartilage may lose its structure and density resulting
in an inability to withstand the normal forces placed on the joint. In these advanced cases,muscle activity causes the the
involved ends of the bones to be compressed together causing further bone destruction.
Further,the disease can irreversibily change the structure and function of a joint to a degree that other degenerative
changes may occur,especially in the weight bearing joints of the body. Thus,joint destruction can progress to the degree that
joint motion is significantly limited and joints can become markedly unstable.
Inflammation in RA is a very complex process. We velieve it starts when one one of the class of cells that guards the
body against foreign invaders ( in ordinary inflammation these are usually bacteria or viruses) comes into contact with something
that triggers the alarm. One form the alarm takes is a whole battery of chemical messengers,called cytokines,that are released
into the joint.
These recruit other cells,the white blood cells that attack and kills other cells and vacteria. One form this killing
takes is the release into the immediate area of very "corrosive"" chemicals. Joint tissue,an innocent bystander,is damaged.
Furthermore,cytokines stimulate the lining of the joint (synovial lining ) to grow and produce other chemicals
that break down cartilage. Cytokines are released into the blood stream,and cause fever and fatigue. The body is so finely
balanced,there are also cytokines released that tend to damp down the inflammation.
Unfortunately,in the RA joint these "good" cytokines tend to become overwhelmed by the "bad" or pro-inflammatory cytokines.
One of the key cytokines that promote inflammation is TNF-alpha. IL-1 alpha is another-there are many members of the
Glucocorticoid use is the most common form of drug-related osteoporosis,and its long term administeration for disorders
such as RA.Osteoporosis is defined as a skeletal disorder charachterized by comprimisal bone strength predisposing to
an increased risk of fracture. Bone strength reflects the integration of two more of the criterias.
Bone density is expressed as grams per area or volume in any given individual is determined by peak bone mass and amount
of bone loss.Bone quality refers to architecture,turnover,damage accumulation (e.g., microfractures) and minerilization.
It is important to acknowledge a common misperception is that osteoporosis is always the result of bone loss. Bone loss
commonly as one ages,but an individual who does not reach optimal (i.e. peak) bone mass during childhood, and adolescense
may develop osteoporosis without the occurrance of accellerated bone loss.
Hence sub optimal bone growth in childhood and adolescence is an important as bone loss to the development of osteoporosis.