New MSK Pathology Lectures Flashcards
What is the most common form of joint disease?
Osteoarthritis
What are some features of osteoarthritis?
Degenerative changes in the articular cartilage, structural changes, functional impairment, related to aging and biomechanical stress, aches and pains worse with use
What are the two kinds of osteoarthritis?
Primary = insidious, no overt cause, age related (>50) Secondary = predisposing condition, excess/inappropriate weight bearing, deformity, injury, systemic disease, age <50
What joints are normally spared from osteoarthritis?
Wrists, elbows and shoulders
What are the early events of osteoarthritis pathogenesis?
Injury to chondrocytes and matrix, chondrocytes proliferate = release inflammatory mediators, proteases, collagen and proteoglycans, remodelling and degradation of cartilage
What are the late events of osteoarthritis pathogenesis?
Inflammatory changes in synovium and subchondral bone, repetitive injury and chronic inflammation causes loss of chondrocytes, disruption to and loss of cartilage matrix
What are the early pathological changes in osteoarthritis?
Damage to cartilage, clusters of chondrocytes, small fissures in cartilage, fibrillation
What are the later pathological changes in osteoarthritis?
Cartilage is completely worn away, subchondral cysts, eburnation, remodelling, osteophyte formation
What is rheumatoid arthritis?
Chronic autoimmune inflammation, systemic and presents with features of arthritis
What are some features of rheumatoid arthritis?
More common in 20-40 year olds, 3:1 female to male ratio, vague systemic features of malaise and fever, generalised MSK pain
How does rheumatoid arthritis affect the joints?
Symmetrical joint involvement, swollen, warm, painful, limited movement in morning and after inactivity, affects small joints before large joints, typically hands, feet, wrists, ankles, elbows, knees and cervical spine, usually spares hips and lumbosacral joints
What is the progression of rheumatoid arthritis?
Joint swelling, decreased ROM, joint fusion
Associated involvement of tendons and ligaments, synovial herniation (cysts)
Joint effusions, peri-articular bone loss, loss of articular cartilage
What is ankylosis?
Joint fusion
What is the acute presentation of rheumatoid arthritis?
Severe symptoms and polyarticular disease, occurs in 10% of patients
What alleles are linked to rheumatoid arthritis?
HLA DRB1 alleles = common structure in beta chain (shared epitope), creates site for binding arthritogens and initiates autoimmune inflammation
What are some environmental factors linked to rheumatoid arthritis?
Infection and smoking
What are some features of the immunology of rheumatoid arthritis?
Cytokine production due to initiation of inflammation
IFNg activates macrophages and synovial cells
IL-17 recruits neutrophils and monocytes
TNF and IL-1 stimulate production of proteases from synovium
RANKL expressed on activated T cells stimulates bone resorption
What are some skin features of rheumatoid arthritis?
Rheumatoid nodules, small vessel vasculitis, pyoderma gangrenosum, associated with episcleritis, pleural and pericardial effusions
What are some features of rheumatoid nodules?
Occur in 25% off patients, often severe disease, pressure points, internal organs involved, necrotising granuloma
What are some features of necrotising granulomas?
Central area of collagen, surrounding palisade of macrophages
What are some manifestations of small vessel vasculitis?
Splinter haemorrhages, peri-ungual infarcts, ulcers, gangrene
What are some ocular and oral manifestations of rheumatoid arthritis?
Ocular = keratoconjunctivitis, episcleritis, scleritis Oral = salivary gland swelling, Sjogren's syndrome
What are some GI and renal manifestations of rheumatoid arthritis?
GI = mesenteric vasculitis (rare), related to medication Renal = forms of glomerulonephritis, amyloid disease
What are some pulmonary and cardiac features of rheumatoid arthritis?
Pulmonary = pleuritis and effusion, rheumatoid nodules, interstitial fibrosis Cardiac = pericarditis and effusion, myocarditis, endocarditis
What are some neurological and general manifestations of rheumatoid arthritis?
Neurological = peripheral neuropathy, cervical myelopathy General = anaemia, lymphadenopathy, splenomegaly
What are some features of seronegative spondyloarthritides?
Group of disease with some common features = HLA B27 associated, no rheumatoid factor, involve sarco-iliac joints +/- others, affect ligamentous attachments
What are some examples of seronegative spondyloarthritides?
Ankylosing spondylitis, reactive arthritis, enteritis associated arthritis
What are some features of ankylosing spondylitis?
Occurs in 20s or 30s, destructive arthritis = sacro-iliac and intervertebral joints, bony ankylosis
What are some features of reactive arthritis?
Arthritis, non-gonococcal urethritis/cervicitis and conjunctivitis, autoimmune reaction to infection (Chlamydia, shigella, salmonella, Yersinia, campylobacter)
What are some features of enteritis associated arthritis?
High lipopolysaccharides in cell wall trigger immune reaction, resolves (may take a year)
What are some features of psoriatic arthritis?
Occurs in >10% of psoriasis patients, predominantly affects joints of hands and feet, 20% of cases involve sacro-iliac joints, may be asymmetrical, similar histology to rheumatoid
What are some features of infectious arthritis?
Potentially destructive process, forms pus, haematogenous spread of organisms, typically involves single joint (usually knee)
How does infectious arthritis present?
Systemic features of infection, acutely painful and swollen joint (aspirate purulent fluid for diagnosis)
What are some organisms that cause infectious arthritis?
S. aureus in adults, H.influenza in young children, gonococcal infection in young adults, Salmonella in patients with sickle cell, myobacterium, Lyme disease, viral
What are some predisposing factors to gout?
Duration of hyperuricaemia (20-30 years), genetic predisposition, alcohol, obesity, drugs
What is classed as osteopenia?
1-2.5 SD below mean peak bone mass
What is osteoporosis classed as?
> 2.5 SD below mean peak bone mass
What does osteoporosis increase the risk of?
Fractures (both atraumatic and vertebral compression)
What are the classes of osteoporosis?
Localised or generalised (primary or secondary)
What are some associations of primary generalised osteoporosis?
Idiopathic, menopausal, senile
What are some causes of secondary generalised osteoporosis?
Endocrine disorders = Cushing’s, hyperparathyroidism, hyperthyroidism
GI disorders = hepatic insufficiency, malabsorption, malnutrition, vitamin C and D deficiency
Alcohol, corticosteroids, immobilisation
What hereditary factors influence osteoporosis?
Polymorphisms in genes regulating osteoclastic activity and vitamin D receptors
What age related changes influence osteoporosis?
Reduced proliferative and biosynthetic capacity of osteoblasts, response to growth factors attenuated
What are some other influences on osteoporosis?
Calcium and reduced physical activity
How does oestrogen cause osteoporosis?
Low oestrogen causes high bone turnover but osteoclasis exceeds osteoblastic activity
What causes osteomalacia?
Vitamin D deficiency = vitamin D needed to stimulate calcium absorption (this causes osteoblast to release osteocalcin)
How does vitamin D deficiency lead to hypocalcaemia and elevated PTH?
Increased calcium absorption and osteoclastic activity which increases release of calcium from bone
Reduced renal calcium loss and increased renal excretion of phosphate (impairs bone mineralisation)
What happens to the bone in osteomalacia?
Bone remodelling occurs normally but newly formed osteoid is not fully mineralised (thick osteoid seams), bone is weakened so prone to fractures
What are some features of avascular necrosis?
Necrosis of bone and marrow, can be asymptomatic, resultant bone and joint damage can lead to THR, loss of effective vascular supply, risk of secondary osteoarthritis
What are some predisposing factors to avascular necrosis?
Alcohol, corticosteroids, bisphosphonate, connective tissue disorders, decompression, sickle cell disease, infection, pregnancy, pancreatitis, radiation
What does avascular necrosis look like histologically?
Usually wedge shaped infarct and often subchondral
What does PTH do?
Activates osteoclasts = increases bone resorption and calcium release
Increases resorption of calcium by renal tubules and urinary excretion of phosphate
Increases synthesis of active forms of vitamin D
How does calcium normally interact with PTH?
Normally inhibits PTH release (but not in hyperparathyroidism)
What are some features of hyperparathyroidism?
Elevated serum calcium, continued osteoclasis so decreased bone mass (more prone to fractures, deformity and degenerative joint diseases), osteoporosis, brown tumours, osteitis fibrosa cystica (rare)
What are some features of the osteoporosis that occurs in hyperparathyroidism?
Generalised, phalanges, vertebrae and femur, prominent changes in cortical bone, medullary cancellous bone also affected (dissecting osteitis), fibrovascular tissue in marrow spaces
What are some features of brown tumours?
Osteoporotic bone prone to fracture and associated haemorrhage elicits macrophage reaction and processes of organisation and repair, includes giant cells, mass of reactive tissue, can become cystic
What are the three stages of Paget’s disease?
Osteolytic = resorption pits with large osteoclasts
Mixed = osteoclasis and osteoblastic activity
Osteosclerotic
What are some features of Paget’s disease?
Bone matures but is soft and porous, occurs in late adulthood, more common in men
What secondary malignancies can arise from Paget’s disease?
Osteosarcoma, fibrosarcoma
