Patogenesis osteoarthritis

Terdapat dua jenis makromolekul utama pada kartilago, yaitu Kolagen tipe dua dan
Aggrekan. Kolagen tipe dua terjalin dengan ketat, membatasi molekul – molekul aggrekan di
3132
antara jalinan-jalinan kolagen. Aggrekan adalah molekul proteoglikan yang berikatan
dengan
asam hialuronat dan memberikan kepadatan pada kartilago.
Kondrosit, sel yang terdapat di jaringan avaskular, mensintesis seluruh elemen yang
terdapat
pada matriks kartilago. Kondrosit menghasilkan enzim pemecah matriks, sitokin
{Interleukin-
1 (IL-1), Tumor Necrosis Factor (TNF)}, dan faktor pertumbuhan. Umpan balik yang diberikan
enzim tersebut akan merangsang kondrosit untuk melakukan sintesis dan membentuk
molekul-molekul matriks yang baru. Pembentukan dan pemecahan ini dijaga
keseimbangannya oleh sitokin faktor pertumbuhan, dan faktor lingkungan.
Kondrosit mensintesis metaloproteinase matriks (MPM) untuk memecah kolagen tipe dua
dan aggrekan. MPM memiliki tempat kerja di matriks yang dikelilingi oleh kondrosit. Namun,
pada fase awal OA, aktivitas serta efek dari MPM menyebar hingga ke bagian permukaan
(superficial) dari kartilago. Pada proses timbulnya OA, kondrosit yang terstimulasi akan
melepaskan aggrekan dan kolagen tipe dua yang tidak adekuat ke kartilago dan cairan sendi.
Aggrekan pada kartilago akan sering habis serta jalinan-jalinan kolagen akan mudah
mengendur. Akibatnya terjadi perubahan struktur sendi, biokimia, metabolik pada sendi
termasuk kartilago sebagai berikut :
1)
Structural changes
Mainly are reductions in stainable proteoglycan, fibrillation, collagen crumping,
chondrocyte multiplication or migration and loss of cartilage. Initially, localized areas of
softening present a pebbled texture at surface followed by disruption along collagen
fiber planes (tangential flaking, vertical fibrillation). As deep clefts are formed in
cartilage, nearby matrix gets depleted of metachromatic material indicating loss of
proteoglycans. Subsequent focal proliferation of chondrocytes occurs as an attempt at
local self-repair leading to irregularly shaped hyaline and fibro cartilage. Later new bone
formation occurs in subchondral bone and at joint margins (osteophytes). Subarticular
cysts predominate wherever overlying cartilage is thin or absent. Separated fragments
of cartilage and bone may form loose bodies, undergo dissolution or become
incorporated into synovium and proliferate locally. Synovium becomes thick and
hypertrophied and capsule contracts with infiltration of lymphoid follicles, lymphocytes
and macrophages. Calcification may occur as calcium crystals deposit in cartilage with
presumed secondary uptake in synovium. Despite loss of bone and cartilage in some
parts of joint, net effect of new cartilage and bone formation is an increase in joint size
and remodelling of shape.
2)
Metabolic and biochemical changes in osteoarthritis cartilage
-
Generalized – Increased hydration and swelling with loss of tensile strength is noticed
in early OA, whereas increase in type I collagen synthesis and progressive fall occurs
in proteoglycan concentration in later stage of OA
-
Specific collagens – Initial swelling of collagen fibrillar network with loss of type II
collagen, specific cleavage of collagens and loss of tensile strength with increased
content of collagen type IV. Type III and X collagen are also synthesized
-
Proteoglycans – Increased extractability and decrease in monomer size because of
specific cleavages by aggrecanases and metalloproteinases.
-
Cytokines, proteinases and inhibitors – There is increase in pro- inflammatory
cytokines, aggrecanases, MMPs (matrix metalloproteinase), cathepsins and decrease
in overall inhibitors (TIMP etc.).
-
Of the three major MMPs (1, 8, and 13) that degrade native collagen, MMPs -13 is
most important, as it preferentially degrades type II collagen whose expression is
greatly increased in OA. The aggrecanases belong to a family of extracellular 33
proteases known as disintegrin and metalloproteases with thrombospondin motifs
(ADAMTS). ADAMTS-4 and ADAMTS-5 appear to be major enzymes in cartilage
degeneration in arthritis. Where as, IL-1beta synthesized by mononuclear cells
(including synovial cells) in inflamed joint is considered by many investigators as a
prime mediator in cartilage matrix degradation and stimulates synthesis and
secretion of many degradative enzymes in cartilage including latent collagenase,
stronelysin, gelatinase and tissue plasminogen activator.

Gambar 11. Pathogenesis of osteoarthritis, including the progression of the osteoarthritis (OA)
positive feedback loop, including synovial inflammation and tissue degradation. Inflammatory
proteins produced mainly by chondrocytes, synovial fibroblasts, and macrophages induce the excess
production of tissue-degrading enzymes, such as matrix metalloproteinases. Products of cartilage
breakdown are phagocytosed by the synovial cells triggering the release of even more
proinflammatory proteins.
6. Patofisiologi tanda gejala
1)
Pain : This is due to stimulation of capsular pain fibers, mechanoreceptors (increased
intra-articular pressure due to synovial hypertrophy), periosteal nerve fibers and by
perception of subchondral microfractures or painful entheses and bursae.
Osteofit merupakan salah satu penyebab timbulnya nyeri. Ketika osteofit tumbuh,
inervasi neurovaskular menembusi bagian dasar tulang hingga ke kartilago dan menuju
ke osteofit yang sedang berkembang. Hal ini menimbulkan nyeri.
2)
Stiffness : With rest, the joint fluid is soaked up by the cartilage within the joint similar
to how a sponge soaks up water. When the joint is used, the cartilage is "squeezed" and
the joint fluid bathes the joint. The more the joint is used, the more the joint fluid coats
and lubricates the inner joint.
3)
Crepitation/rasa gemeratak yang timbul pada sendi yang sakit : due to irregularity of
articular surface, bony enlargement due to remodelling and osteophytes, deformity,
instability, restricted ability and stress pain.
4)
Nodal generalized osteoarthritis : Present commonly as polyarticular, finger I-P joint
involvement, Heberden (distal I-P joint) and Bouchard (proximal I-P joint) nodes.
5)
Pembengkakan sendi yang asimetris : dikarenakan terjadi efusi pada sendi yang biasanya
tidak banyak ( < 100 cc ) atau karena adanya osteofit, sehingga bentuk permukaan sendi
berubah.
6)
Pembesaran sendi (deformitas) : Sendi yang terkena secara perlahan dapat membesar. 34
7)
Tanda – tanda peradangan : nyeri tekan, gangguan gerak, rasa hangat yang merata, dan
warna kemerahan, dapat dijumpai pada OA karena adanya synovitis. Biasanya tanda –
tanda ini tidak menonjol dan timbul pada perkembangan penyakit yang lebih jauh.
8)
Perubahan gaya berjalan : Keadaan ini selalu berhubungan perubahan struktur sendi
dan nyeri karena menjadi tumpuan berat badan terutama pada OA lutut.
9)
Pembengkakan sendi (swelling in a joint) : Sendi membengkak / membesar bisa
disebabkan oleh radang sendi dan bertambahnya cairan sendi atau keduanya.