Pathophysiology

Synovium

A cells: phagocytic
B cells: secrete synovial fluid (proteins + hyaluronate)

Synovial fluid is a "boundary layer" fluid, providing lubrication and also adhesion if stress forces applied to joint.

Articular hyaline cartilage

Chondrocytes: manufacture proteoglycan matrix and fibrous network.
Collagen fibres: 3-D lattice of type II collagen fibres arranged like bedsprings. Shock-absorption.
Proteoglycan matrix: water-attracting to improve shock-absorption.

Fibrocartilage

Less proteoglycan matrix
More fibrous: Type I collagen fibres which are aligned in parallel bundles, making it resistant to shearing forces eg menisci in knee.

Juxta-articular bone

Trabecular bone for shock-absorption.

Joint capsule and ligaments

Type I collagen.
Good nerve and blood supply.

Enthesis

Plane of attachment between bone and muscle tendon.

Pathogenesis of RA

Antigen (?viral) provokes immune response within synovial tissue. This immunological reaction leads to release of inflammatory mediators such as kinins, which stimulate other inflammatory cells causing chronic inflammation. Phagocytic neutrophils are drawn into the synovial tissue and lysosomal enzymes are released. The synovium becomes oedematous and more vascular. Granulation tissue called pannus is formed, which is rich in tissue digestive enzymes. This invasive tissue produces erosions.

Genetic link: chromosome 6 contains the genes of the major histocompatibility complex (MHC) which encode for the proteins known as human lymphocyte antigens (HLA).

MHC gene code is mapped as follows:

Class II histocompatibility antigens:

HLA-DP
HLA-DQ
HLA-DRB

Class III histocompatibility complex:

Genetic code of some of the complement cascade.
Genetic code for tissue necrosis factor (TNF)

Class II histocompatibility complex:

HLA-C
HLA-B
HLA-A

Some associations:

HLA-B27 with ankylosing spondylitis and other seronegative spondyloarthropathies.
HLA-DR4 with RA.
HLA-DR4 subgroups DW4 and DW14 with progressive severe RA.

Osteoarthritis

Alteration of the proteoglycan matrix of the cartilage results in increased water content. This reduces the shock-absorber effect, and roughening and fibrillation of the surface occurs, leading to increased friction. The cartilage thins, and raw bone ulcerates through. Attempts at self-repair then occur. There is an increase in vascularity and remodelling of the bone surface is attempted. There is sclerosis of the bone and bone cysts are formed, filled with connective tissue chondrocyte cells. Osteophytes develop from peri-articular fibrocartilage. This all results in the release of debris in the form of cartilage degradation products and bone hydroxyapatite crystals, which causes synovitis and the release of further tissue-digesting enzymes. A joint effusion develops, which stretches the joint, so causing further tissue damage.

Gout

Dietary purines: red wine, liver, sardines, mackerel.
DNA purines are broken down into xantines then uric acid (pyrimidines are broken down into urea). Deposition of monosodium urate monohydrate crystals in jointspace.
Primary: in 30% of patients with familial xanthine oxidase enzyme abnormalities.
Secondary: diuretics, renal failure, starvation, myeloproliferative disease, cytotoxics, dehydration.