· three parts
· synovitis
· vasculitis
· secondary changes
Angiogenesis
· first stage
· due to vascular budding and invasion of synovium
· result of some vasculoproliferative factor released by activated cells
Inflammatory infiltrate
· circulating lymphocytes adhere to and migrate through walls of newly formed vessels
· enhanced by growth factors
· more T-lymphocytes than B-lymphocytes
· helper T-cells cause B cell proliferation and transformation into antibody secreting cells
Hyperplasia
· increase in number of cells
· intima hypertrophies from 1-2 cells thick to up to 10 cells thick
· further proliferation of blood vessels and fibroblasts
· synovium forms frond-like villi
· 1 cm high and 2 mm thick
· significant increase in surface area
Destruction
· inflamed hyperplastic synovium secretes destructive agents
· enzymes degrade articular cartilage
· exudate of fluid
· produces synovial effusion
· fluid is inflammatory
· turbid
· thin with low viscosity
· WCC of 20-50 x 109/l
· most of cells are polymorphs
· immune complexes present
· lead to further inflammatory infiltrate
· hyaluronate depolymerised
· leads to decreased viscosity
· synovial fluid often contains copious amounts of fibrinoid material
· may appear as innumerable ‘rice bodies’
· normal intra-articular pressure is subatmospheric
· pressure in affected joint increases because
· volume of synovial fluid increases
· capsule thickened with loss of compliance
· pressure increased with exercise
Bone
· synovial fluid forced through weak areas of cartilage
· hydrodynamic effect results in enlargement of cavity
· result is subarticular cyst
Soft tissue
· synovial fluid forced into periarticular soft tissues
· results in soft tissue cyst
· most common is popliteal cyst
Capillary
· intra-articular pressure may exceed capillary pressure
· leads to relative intra-articular anoxia despite increased vascularity
· similar synovitis occurs in tendon sheaths
· tendon sheath becomes thickened
· synovitis results in impaired movement of tendons
· mechanical impedence
· fibrosis and adhesion between synovial layers or tendons
· tendon rupture may occur due to
· invasion of tendons by inflammatory reaction
· vasculitis
Enzymatic destruction
· enzymes released into synovial fluid by
· inflamed synovium
· activated chondrocytes
· dead polymorphs
· leads to enzymatic degradation of proteoglycans of cartilage
· initiated by metalloproteases
· propagated by removal of enzyme inhibitors
· followed by degradation of collagen
· proteases destroy cross-links
· collagen then becomes soluble
· denatured collagen digested by collagenases
Destruction by pannus
· proliferating synovium penetrates synovial-cartilage junction
· produces angular erosion
· undermines cartilage and separates it from subchondral bone
· bone then excavated
· synovium also spreads over surface of cartilage
· called pannus
· causes direct destruction of cartilage
Response
· mechanical properties of cartilage lost
· fragmentation occurs
· starts at surface
· extends into deeper layers
· articular cartilage replaced by fibrocartilage and fibrous tissue
· contains type I and II collagen
· architecture not recreated
· inflammatory changes occur
· hyperaemia of bone leads to
· periarticular osteopaenia
· precocious epiphyseal development with early physeal closure in young bones
· hyperaemia of periosteum leads to
· thickening of bone shafts adjacent to joint
· periostitis
· three forms
Necrotising arteritis
· luminal thrombosis and adventitial infiltrate
· of small and medium arteries
· may cause
· neuropathies (esp. mononeuritis)
· mesenteric infarction
· parenchymal lung changes
Subacute arteritis
· vessels surrounded by lymphocytes
· fibrosis occurs
· blood flow unimpaired so few effects
· causes nodule formation
Fibromuscular hyperplasia
· fibrosis and proliferation of intima
· gradual occlusion of lumen
· thrombosis can then occur
· causes digital arteritis
· most characteristic feature of vasculitis
· initiated by pressure or trauma
· cause of vasculitis is type III (Arthus) reaction
· IgM and IgG rheumatoid factors form complexes
· deposited on wall of blood vessels
· chemotactic effect attracts polymorphs
· inflammation augmented and vasculitis produced
· intense fibrous reaction around blood vessel
· necrosis occurs in centre of nodule
· due to microinfarcts and proteinases
· called necrobiosis
· central necrosis surrounded by pallisade of histiocytes and multinucleated giant cells
· outer layers are fibrous tissue
· seen in
· skin
· vocal cords
· cardiac valves
· lungs and pleura
Lung lesions
· may see
· intrapulmonary granulomas
· associated interstitial pulmonary fibrosis
· pleural effusions and fibrosis
· may slowly progress to pulmonary failure
· lung changes may also be induced by gold, penicillamine and methotrexate
Heart lesions
· may see
· intracardiac granulomas
· valvular nodules
· pericardial effusions and fibrosis
· rarely cause problems
Kidney lesions
· changes due to rheumatoid nonspecific and of little significance
· may see
· papillary necrosis from phenacatin abuse
· associated amyloidosis with renal failure
Sjogren’s syndrome
· dry mouth, nose, eyes and ears
· due to infiltration of secretory glands and secretory surfaces by lymphocytes