Pathogenesis Of Rheumatoid Arthritis Biology Essay

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Rheumatoid get a name from the word "rheuma", meaning a stream of morbid humours that considered to flow through the body, symptoms with aches and pain. (46) The cause of the Rheumatoid Arthritis is unknown. There are 1 percent of world population who affected Rheumatoid Arthritis. Women are 3 times more affected than men and it can affect on any age but mostly affect between 40 to 50 ages which can be disabling that can lead to loss of functioning and mobility to joint.(54)

Rheumatoid Arthritis is a common chronic inflammatory and destructive arthropathy that cannot be cured and that has substantial personal, social, and economic costs. There is 80% percent of the Rheumatoid arthritis patients become disable after 20 years.(77) Rheumatoid Arthritis is an autoimmune disease that can attack health body tissues and synovium. The synovium is the tissues which are surrounding each the joint. Those synovium tissues are producing the synovial fluid which makes to lubricate the joint between the two bones. The autoimmune system produces the antibodies is proteins to attack the viruses, bacteria and other germs from human body.(10,76) That autoimmune attacks against body tissues the synovium. Then the affected joint becomes inflammation that will damage the joint cartilage and the bone near the joint.(76)

Pathogenesis of Rheumatoid Arthritis

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The synovial membrane in patients with rheumatoid arthritis is characterized by hyperplasia, increased vascularity, and an infiltrate of inflammatory cells, primarily CD4+ T cell, which are the main orchestrator of cell-mediated immune responses. In genetic studies, rheumatoid arthritis is strongly linked to the major histocompatibility-complex class II antigens HLA-DRB1*0404 and DRB1*0401. (51) The main function of HLA class II molecules is to present antigenic peptides to CD4+ T cells, which strongly suggests that rheumatoid arthritis is caused by an unidentified arthritogenic antigen(36) the antigen could be either an exogenous antigen, such as a viral protein, or an endogenous protein. Recently, a number of possible endogenous antigens, including citrullinated protein, human cartilage glycoprotein 39, and heavy-chain-binding protein, have been indentified.(4)

Cellular mediators of Inflammation and Joint Damage

Antigen-activated CD4+T cells stimulated monocytes, macrophages, and synovial fibroblasts to produce the cytokines interleukin-1, interleukin-6, and TNF-α and to secrete matrix metalloproteinases (Fig.1) through cell-surface signalling by means of CD69 and CD11 (43) as well as through the release of soluble mediators such as interferon-γ and interleukin-17.interleukin-1, interleukin-6 and TNF-α are the key cytokines that drive inflammation in rheumatoid arthritis. Activated CD4+ T cells also stimulate B cells (Fig1), through cell-surface contact and through the binding of α1β2 integrin, CD154 (CD40 ligand), and CD28, to produce immunolobulins, including rheumatoid factor. The precise pathogenic role of rheumatoid factor is unknown, but it may involve the activation of complement through the formation of immune complexes. Activated CD4+ T cells express osteoprotegerin ligands that stimulate osteoclastogenesis (Fig.1). Such activated T cell caused joint damage in an animal model of rheumatoid arthritis(50).

These activated macrophages, lymphocytes, and fibroblasts, as well as their products, can also stimulate angiogenesis, which may explain the increased vascularity found in the synovium of patients with rheumatoid arthritis. Endothelial cells in the synovium are activated and express adhesion molecules that promote that recruitment of inflammatory cells into the joint. This process is enhanced by the release of chemokines, such as interleukin-8, by inflammatory cells in the joint. The detailed mechanisms of these complex cellular interactions remain exclusive.

Soluble Mediators of Inflammation and joint Damage

Monocytes, macrophages, fibroblasts, and T cells produce numerous cytokines for stimulation. These cytokines including TNF-α and interleukin-1 can be detected in synovial fluid from Rheumatoid Arthritis patients.(41) Both TNF-α and interleukin-1 are likely to have primary roles in the pathogenesis of rheumatoid arthritis. The serum and synovial concentrations of both cytokines are high in patients with active rheumatoid arthritis. TNF-α and interleukin-1 are potent stimulators of mesenchymal cells, such as synovial fibroblasts, osteoclasts, and chondrocytes, that release tissue-destroying matrix metallo-proteinases.(78) Interleukin-1 and TNF-α also inhibit the production of tissue inhibitors of metalloproteinases by synovial fibroblasts. These dual actions are thought to lead to joint damage. Perhaps by inducing the production of interleukin-II TNF-α stimulates the development of osteoclasts, which are responsible for bone degradation.(35)

TNF-α

TNF-α is a potent cytokine that exerts diverse effects by stimulating a variety of cells. It is a soluble 17-kd protein composed of three identical subunits. It is produced mainly by monocytes and macrophages, but also by B cells, T cells, and fibroblasts. TNF-α is inserted into the cell membrane and released through the cleavage of its membrane-anchoring domain by a serine metalloproteinase. TNF-α secretion might be suppressed by inhibitors of this enzyme. (56)

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TNF-α ability is to promote inflammation. TNF-α is an autocrine stimulator as well as a potent paracrine inducer of other inflammatory cytokines, including interleukin,1 interleukin-6,interleukin-8, and granulocytemonocyte colony-stimulating factor.(62,37) TNF-α also increase the inflammation by stimulating fibroblasts to express adhesion molecules, such as intercellular adhesion molecule 1. (12)

TNF-α is important role in Rheumatoid synovitis as an inflammatory cytokine. The synovial cells from patients with rheumatoid arthritis, blocking TNF-α with antibodies significantly reduced the production of interleukin-1, interleukin-6, interleukin8, and granulocyte-monocyte colony-stimulating factor. The blockade of TNF-α may have a more global effect on inflammation than the blockade of other cytokines present in high concentrations in synovial fluids.(9)

Interleukin-1

Interleukin-1, a 17kd protein was mostly produced by monocytes and macrophages. Endothelial cells, B cells and activated T cells also produced Interleukin-1. (49) The interleukin-1 signalling system is more complex than the TNF-α system. Studies of arthritis in animals have strongly involved interleukin-1 in joint damage. Injection of interleukin-1 into the knee joints of rabbits results in the degradation of cartilage, (69) whereas the injection of antibodies against interleukin-1 ameliorates collagen-induced arthritis and decrease the damage to cartilage in mice. Macrophages in the synovial tissue of patients with rheumatoid arthritis appear to be an important source of interleukin-1. (92) TNF-α, interleukin-1 may cause damage by stimulating the release of matrix metalloproteinases from fibroblasts and chondrocytes. The concentrations of interleukin-1 receptor antagonist are high in the synovial fluid of patients with rheumatoid arthritis, but not high enough to suppress inflammation. (13)

Sign and Symptom of Rheumatoid Arthritis

The symptoms of Rheumatoid Arthritis patient start with pain and stiffness in one or more joint and the amount of pain and stiffness slowly increase, sometimes the patients got low grade fever, loss of energy and patients feel very fatigued after recovering from cold or flu. Rheumatoid arthritis starts very differently in different person. Some of the patient only feels increasing the stiffness without feeling the pain but some patients feel too much pain at their joint from the beginning of the disease. But, some patients feel pain and swelling that appear suddenly and just disappear quickly.

The first stage of the Rheumatoid Arthritis is muscle and joint stiffness mostly happen in the early morning, called morning stiffness. Rheumatoid Arthritis is not only effect on one joint but it can also effect on every part of the body. The most commonly involved in rheumatoid arthritis are finger joints, wrists, elbows, and shoulders, some joints in the neck jaw, hip, knees, ankles, food and toe joints.(44,55)

Skin

Some rheumatoid arthritis patients have small nodules on the skin around the effected joint. The nodules will be noticeable when the joints are flexed. There is the skin problem which is associated with Rheumatoid, as known as Purpura. Pupura means purplish patches on the skins that damage the blood vessels which causing the bleeding to the skin.(41)

Eyes and mouth

There are 15 percents of Rheumatoid Arthritis Patient with Sicca Syndrome also known as the Sjogren syndrome which is inflammatory disease that cause dry eyes and dry mouth. That syndrome affect to the two set of structure that produces the tears and a set of gland which help the moisture of eyes. Rheumatoid Arthritis can affect those structures that decrease of tear production. It can make dry eyes and feel too much hurt on the eyes. That can cause the loss of eyes vision.

Sometimes Rheumatoid Arthritis also affect to the mouth which cause by inflammation to the salivary glands that can cause the dry mouth is decrease in saliva can prompt tooth decay.(81)

Heart Risk of Rheumatoid Arthritis

Rheumatoid arthritis' patients have the higher risk to get the heart disease than normal person. Rheumatoid arthritis can also affect between heart and pericardium without any symptoms. Rheumatoid arthritis patients are very easy to get the heart attack that is so painful for the heart and suddenly cardiac death because Rheumatoid Arthritis make inflammation of the heart tissues and can easily get depression.(17)

Blood and Blood Vessels

The major blood testing of rheumatoid arthritis is to determine whether they have anemia that means decrease range of red blood cells and it is strongly reflect the arthritis activity. When the arthritis is caused, the anemia of chronic disease develops. In this case, the drug erythropoietin can be used intravenously to raise red blood cell production for a short time. Anemia may improve an unusual complication of rheumatoid arthritis called Felty's syndrome that occurs very fewer in Rheumatoid Arthritis patients. Rheumatoid Arthritis patients with Felty's syndrome improve an enlarged spleen and reduced white blood cell count. Other two effects of Felty' syndromes are skin ulceration and dark patches of skin. So, disease-modifying antirheumatic drugs (DMARDs) are used for Felty' syndrome treatment therapy. (81)

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Rheumatoid Arthritis is greater risk of causing osteoporosis that is thinning of the bone or loss of bone mass. Pro -inflammatory cytokines stimulate osteoprotegrin and this osteoprotegrin is stimulating the activity of osteoclasts that is destroy the bone. In menopause situation, osteoclasts are more than osteoblasts (bone-building cells) so bone loss happen in skeletal growth. Therefore women with Rheumatoid Arthritis are more causing the bone loss than men because men are not caused absolutely from this situation. (81)

Lung

This autoimmune disease can develop a nodule in lung but there is no symptom and sign for that kind of nodules.(19) Rheumatoid arthritis can affect the lung's lining tissues that can be stiffness of lung tissues or over growth which is usually harmless but it can collapsed the lung that affect on breating, cough and fever. Some Rheumatoid Arthritis treatment also can affect on the lung.