A. Gout → III: Inflammation due to deposition of uric acid (monosodium urate) crystals in joints.
B. Rheumatoid arthritis → I: Autoimmune disease. Immune system attacks synovial membrane → destroys cartilage and bone.
C. Osteoporosis → II: Reduction in bone mass. Bones fragile, prone to fractures. Common in post-menopausal women.
D. Osteoarthritis → IV: Mechanical wearing away of articular cartilage at joint ends. Degenerative, not autoimmune.
Joint disorders can be classified as: Inflammatory: rheumatoid arthritis (autoimmune), gout (crystal-induced), septic arthritis (infectious). Degenerative: osteoarthritis (mechanical wear). Metabolic: gout (purine metabolism disorder), pseudogout (calcium pyrophosphate). Autoimmune: RA, systemic lupus erythematosus (SLE), ankylosing spondylitis, psoriatic arthritis. Infectious: septic arthritis (Staphylococcus most common), Lyme disease (Borrelia burgdorferi). Understanding the mechanism helps distinguish between these conditions in clinical and examination settings.
Gout results from hyperuricaemia — elevated serum uric acid. Pathogenesis: purines (adenine, guanine) from food and cell turnover → hypoxanthine/xanthine → uric acid (by xanthine oxidase enzyme). In humans (and great apes): no uricase enzyme → uric acid is the end product of purine metabolism. Other mammals: have uricase → convert uric acid to allantoin (more soluble) → no gout. When serum uric acid > 6.8 mg/dL: supersaturation → monosodium urate crystals form in cool peripheral joints (big toe = podagra, ankle, knee). Crystal deposits trigger NLRP3 inflammasome → IL-1beta release → intense acute inflammation. Treatment: Acute attack: NSAIDs (indomethacin), colchicine (inhibits tubulin → blocks neutrophil migration). Chronic: allopurinol (inhibits xanthine oxidase → reduces uric acid production), febuxostat, probenecid (increases renal uric acid excretion).
RA is a chronic systemic autoimmune disease primarily affecting synovial joints. Epidemiology: affects ~1% of population, women:men = 3:1. Pathogenesis: molecular mimicry or other triggers → CD4+ T helper cells activated → attack synovial membrane → synovitis (inflammation of synovium). T cells activate B cells → produce rheumatoid factor (IgM anti-IgG antibody) and anti-CCP antibodies (anti-citrullinated protein — most specific test). Inflammatory cytokines (TNF-alpha, IL-1, IL-6) → pannus formation (invasive synovial tissue) → destroys cartilage and underlying bone → joint deformity. Features: symmetrical joint involvement (unlike gout which is asymmetric), morning stiffness >1 hour, metacarpophalangeal (MCP) joints affected, systemic features (fatigue, anaemia, vasculitis). Treatment: NSAIDs, DMARDs (methotrexate — first line), biologics (anti-TNF: etanercept, adalimumab, infliximab), JAK inhibitors.
Osteoporosis: skeletal disorder characterised by low bone mass and microarchitectural deterioration → increased fracture risk. Bone density measured by DEXA scan. T-score: comparison to young healthy adult mean. T-score < -2.5 = osteoporosis. T-score -1.0 to -2.5 = osteopenia (pre-osteoporosis). Risk factors: female sex, post-menopause (oestrogen loss → reduced OPG → increased RANKL → more osteoclast activity → bone resorption), age, smoking, alcohol, low calcium/vitamin D intake, sedentary lifestyle, corticosteroid therapy (most common cause of secondary osteoporosis), family history. Fragility fractures: wrist (Colles fracture), vertebral compression fractures, hip fracture. Prevention: adequate calcium (1000-1200 mg/day), Vitamin D (800-2000 IU/day), weight-bearing exercise, quit smoking. Treatment: bisphosphonates (alendronate, risedronate — inhibit osteoclasts), denosumab (anti-RANKL antibody), teriparatide (PTH analogue — stimulates osteoblasts).
OA is the most common joint disease globally. Pathogenesis: mechanical stress → damage to articular cartilage → chondrocyte dysfunction → reduced proteoglycan and collagen synthesis → cartilage thinning and fibrillation. Subchondral bone changes: sclerosis (hardening), osteophytes (bone spurs). Synovial inflammation: secondary, less severe than RA. Risk factors: age (most important), female sex after 55, obesity (increases joint load), previous joint injury, occupational repetitive stress. Affected joints: knees, hips, hands (DIP joints — Heberden nodes, PIP joints — Bouchard nodes), spine. Symptoms: joint pain worse with use, relieved by rest, stiffness < 30 min (vs RA > 1 hour morning stiffness), crepitus (grating sound/feeling). Treatment: weight loss (most effective for knee OA), exercise, analgesics (paracetamol, NSAIDs), physiotherapy, joint replacement (arthroplasty) for severe disease.
Muscular dystrophies: genetic diseases causing progressive muscle weakness. Duchenne muscular dystrophy (DMD): X-linked recessive. Mutation in dystrophin gene (largest human gene). Dystrophin absent → muscle membrane fragility → progressive muscle degeneration. Onset in childhood. Wheelchair-bound by teens. Becker MD: milder form, dystrophin present but abnormal. Myasthenia gravis: autoimmune. Antibodies against nicotinic ACh receptors at neuromuscular junction → reduced receptor number → muscle weakness. Fatigable weakness (worse with activity, better with rest). Treated: anticholinesterase (pyridostigmine), thymectomy, immunosuppression. Fibromyalgia: chronic widespread pain, fatigue, sleep disturbance. Pathophysiology not fully understood — central sensitisation. Rhabdomyolysis: rapid breakdown of skeletal muscle → myoglobinuria → can cause acute kidney injury. Causes: extreme exercise (marathon running, military training), trauma, drug-induced (statins), infections.
206 bones in adult human. Types by shape: Long bones: humerus, femur, tibia, fibula, radius, ulna, metacarpals, metatarsals, phalanges. Short bones: carpals (wrist), tarsals (ankle). Flat bones: skull, sternum, scapula, ribs. Irregular bones: vertebrae, facial bones. Sesamoid bones: patella (kneecap), pisiform. Types by composition: Compact (cortical) bone: dense outer shell. Contains osteons (Haversian systems). Spongy (cancellous/trabecular) bone: inner mesh-like network. Contains red bone marrow (haematopoiesis). Bone cells: osteoblasts (bone-forming), osteoclasts (bone-resorbing, from monocyte lineage, multinucleated), osteocytes (mature osteoblasts trapped in lacunae — mechanosensors). Bone remodelling: continuous process. ~10% of bone remodelled per year. Regulated by PTH (stimulates osteoclasts via RANKL), calcitonin (inhibits osteoclasts), oestrogen (inhibits osteoclast activity), mechanical loading (stimulates osteoblasts via Wnt pathway).
Joints (articulations) are connections between bones. Classified by structure and movement. Fibrous joints (synarthroses): bones connected by fibrous tissue, no movement. Sutures of skull (interdigitating fibrous connections). Syndesmosis (radius-ulna). Cartilaginous joints (amphiarthroses): connected by cartilage, limited movement. Synchondrosis (growth plates in children — hyaline cartilage). Symphysis (intervertebral discs — fibrocartilage, pubic symphysis). Synovial joints (diarthroses): most common type, freely movable. Articular cartilage (hyaline) covers bone ends. Synovial cavity filled with synovial fluid (lubricates, nourishes cartilage). Synovial membrane: produces synovial fluid (filtrate of plasma + hyaluronic acid, lubricin). Strengthened by ligaments. Types of synovial joints: ball and socket (shoulder, hip), hinge (knee, elbow, ankle), pivot (atlas-axis rotation), condyloid (wrist), saddle (carpometacarpal of thumb), gliding/plane (intercarpal, intertarsal joints).