Hamzah's MSK pathology Flashcards
What is osteoarthritis?
A group of diseases characterised by joint degradation
- usually primary - no clear underlying disorder
- can be secondary to joint disease - gout, rheumatoid arthritis
Epidemiology of OA
- most common joint condition
- F:M = 3:1
- onset = >50 years
Pathophysiology of OA
- progressive destruction and loss of articular cartilage with accompanying periarticular bone response
- low-grade inflammation –> IL1 and TNFalpha leads to the release of metalloproteinases from chondrocytes which degrades the cartilage matrix
- underlying bone is exposed and responds by becoming thickened –> cyst formation
- osteophytes –> cartilaginous growths at margins of the joint which become calcified
Clinical presentation of OA
- symptoms typically worsen during the day with activity
- localised - knee and hip
- pain on movement and crepitus
- background pain at rest
- joint gelling –> stiffness after 30 mins of rest
- joint instability
- bony nodules - Heberden’s nodules=PIP, Bouchard’s nodules=PIP
- mild synovitis
Differential diagnosis of OA
Rheumatoid arthritis
- pattern of joint movement
- absence of systemic features
- RA has marked early morning stiffness
Diagnostic tests in OA
- Radiography shows LOSS
- Loss of joint space
- osteophytes
- subarticular sclerosis
- subchondral cysts
Treatment of OA
- non-pharmacological = weight loss, exercise, physical therapy
- pharmacological - analgesia (paracetamol, NSAIDs (+PPI))
- hyaluronic acid injections
- surgery - joint replacement
What is rheumatoid arthritis?
= A chronic systemic inflammatory disease with a symmetrical, deforming, peripheral polyarthritis
Epidemiology of RA
- prevalence = 1%
- F:M = 2:1
- peak onset = 40-50 years
Aetiology of RA
- pre-menopausal women are significantly more affected than men/post-menopausal women
- FH
- Genetic features - HLA DR4 and HLA DR1
Pathophysiology of RA
- activated T cells, macrophages, mast cells and fibroblasts contribute to inflammation
- local production of rheumatoid factor (autoantibodies against Fc portion of IgG) leads to immune complex formation and complement activation
- infiltration of synovium occurs by immune cells –> synovitis
- angiogenesis of synovium occurs
- synovium proliferates
- pannus formation
- pannus erodes into the articular cartilage and destroys the joint, producing bony erosions
Clinical presentation of RA
- symmetrical, swollen and painful joints - worse in morning
- extra-articular symptoms = fever, fatigue, weight loss, pericarditis
- ulnar deviation of fingers
- Boutonniere and swan-neck deformities
- vasculitis, carpal tunnel syndrome, lymphadenopathy, rheumatoid nodules in elbows and lungs
Differential diagnosis of RA
SLE, OA, psoriatic arthritis, spondyloarthropathies
Diagnostic tests in RA
- Rheumatoid factor (not very specific)
- Anti-cyclic citrullinated peptide antibodies (anti CCP) - highly specific
- XR - soft tissue swelling, loss of joint space, juxta-articular osteopenia
- US/MRI - synovitis
- anaemia of chronic disease
Treatment of RA
- DMARDs - methotrexate
- Biological agents - Infliximab
- NSAIDs for symptom relief
- Physiotherapy and occupational therapy
- Surgery
What is gout?
deposition of monosodium urate crystals in joints
Aetiology of gout
- increased consumption of purines = shellfish, anchovies, red meat
- decreased clearance of uric acid - kidney failure
- DM, CVD, hypertension
Pathogenesis of gout
purines –> uric acid –> urate ion and sodium ion = monosodium urate crystals
Clinical presentation of gout
- acute monoarthropathy with severe joint inflammation
- > 50% occur at metatarsophalangeal joint
- can also affect ankle, foot, hand, wrist, elbow, knee
What are permanent deposits called in chronic gout?
tophi
Differential diagnosis of gout
pseudogout, septic arthritis
Diagnostic tests in gout
- polarised light microscopy of synovial fluid shows white crystals
- serum urate is raised or normal
- radiography - soft tissue swelling, punched out erosions in juxta-articular bone
Treatment of gout
- symptoms subside in 3-5 days
- colchicine - inhibits leukocyte migration
- NSAIDs or etoricoxib (selective COX2 inhibitor)
- Hydrocortisone
- allopurinol - xanthine oxidase inhibotor
What does xanthine oxidase do?
catalyses the conversion of purine to uric acid
How do you prevent gout?
- prophylaxis = allopurinol
- lose weight
- avoid prolonged fasts, alcohol, red meat and low-dose aspirin
What crystals are present in pseudogout?
calcium pyrophosphate
Risk factors for pseudogout
old age, hyperparathyroidism, haemochromatosis, hypophosphatemia
Pathogenesis of pseudogout
- caused by the deposition of calcium pyrophosphate in a joint
- pyrophosphate is a by-product of the hydrolysis of nucleotide triphosphates within chondrocytes
Typical patient with pseudogout…
pseudogout is typically seen in elderly women and usually affects the knee or wrist
Diagnostic tests for pseudogout
- polarised light microscopy of synovial fluid shows calcium pyrophosphate crystals
- XR - soft tissue calcium deposition
Treatment of pseudogout
- acute attacks = cool packs, rest, aspiration, intra-articular steroids
- NSAIDs and colchicine may prevent acute attacks
What is osteoporosis?
reduced bone mass –> increased fracture risk
Epidemiology of osteoporosis
- > 50 women=18%, men=6%
Aetiology of osteoporosis
- inadequate peak bone mass or ongoing bone loss
- glucocorticoids
What is peak bone mass dependant on?
genetics, nutrition, sex hormones, physical activity
How do glucocorticoids cause osteoporosis?
- decrease osteoblast activity and lifespan
- reduce calcium absorption from the gut and increase renal clearance of calcium
- suppress sex hormone production –> increases bone turnover and loss
Risk factors for osteoporosis
SHATTERED
- Steroid use (>5mg/day prednisolone)
- Hyperparathyroidism, hyperthyroidism, hypercalciuria
- Alcohol and tobacco
- Thin (<22BMI)
- Testosterone low
- Early menopause
- Renal or liver failure
- Erosive/inflammatory bone disease - myeloma, RA
- Dietary calcium low, T1DM
Clinical presentation of osteoporosis
Only symptoms tend to be fractures
- thoracic and lumbar vertebrae
- proximal femur
- distal radius (Collie’s fracture)
Diagnostic tests in osteoporosis
- XR
- bone densitometry - DEXA scan - T score less than -2.5=osteoporosis
- bloods - calcium, phosphate and alkaline phosphatase all normal
What is used to guide treatment in osteoporosis?
FRAX tool - gives ten year probability of fracture
Lifestyle measures in osteoporosis
- quit smoking, reduce alcohol consumption
- weight-bearing and balance exercises - reduces fall risks
- calcium and vitamin D supplements
- Home-based falls prevention programme
Pharmacological management of osteoporosis
- Bisphosphonates = first line treatment = alendronate
- Calcium and vitamin D supplements
- HRT - prevents osteoporosis but does not treat
- Denosumab - monoclonal antibody to RANK-L (twice yearly)
What is osteomalacia?
Inadequate bone mineralisation –> soft bones
- children = rickets
- adults = osteomalacia
Causes of osteomalacia
- impaired metabolism of vitamin D, phosphate or calcium
- Vit D deficiency: intestinal malabsorption (coeliac, crohn’s), not enough UV exposure, phenytoin, liver and kidney diseaese
Osteoblasts secrete
osteoid - made of type 1 collagen
- this provides the framework and calcium and phosphate crystals are then deposited
What enzyme is involved in bone mineralisation?
alkaline phosphatase - increases in response to osteoblast activity
How does vitamin D regulate calcium and phosphate?
- inactive vitamin D –> 25-hydroxyvitamin D (liver, 25-hydroxylase)
- 25-hydroxyvitamin D –> 1,25-dihydroxyvitamin D (calcitriol) - (kidneys, 1-alpha hydroxylase)
Calcitriol =
- increases renal absorption of calcium
- increases intestinal absorption of calcium and phosphate
Parathyroid hormone
- secreted in response to low calcium levels
- stimulates calcium and phosphate resorption from bone
- boosts 1,alpha hydroxylase activity –> more vit D absorbed from gut
- increases calcium reabsorption and potassium secretion from the kidneys
Inadequate mineralisation in children
leads to soft bones, impaired growth and malformations
Inadequate mineralisation in adults
weakening and softening of bones –> easier to fracture
Clinical presentation of osteomalacia
- diffuse bone and joint pain
- proximal bone weakness
- bone fragility
- increases risk of fractures
- muscle spasms and numbness
- rickets = delayed closure of fontanelles, bowlegs, prominent frontal bone
Diagnosis of osteomalacia
- Bloods - low vitamin D, calcium, elevated alkaline phosphatase and high PTH
- XR = decreases bone mineral density, loss of cortical bone
- bone biopsy - incomplete bone mineralisation
Treatment of osteomalacia
- oral vitamin D supplementation
- treat underlying cause
- prevention = vit D supplements during pregnancy and to neonates/infants
What are spondyloarthropathies?
- arthritis affecting the spinal column and peripheral joints and enthesitis
- ankylosing spondylitis
- reactive arthritis
- psoriatic arthritis
What is the gene associated with spondyloarthropathies?
HLA B27
What is ankylosing spondylitis?
- chronic inflammatory disease of the spine and sacroiliac joints
- men present earlier
Clinical presentation of ankylosing spondylitis
- male <30 with gradual lower back pain
- spinal morning stiffness relieved by exercise
- pain improves towards the end of the day
- pain radiates from sacroiliac joints to hip/buttock
- enthesitis, iritis, fatigue
- associated with osteoporosis, aortitis, pulmonary fibrosis
Diagnostic tests in ankylosing spondylitis
- XR - bamboo spine, sacroiliitis
- MRI
- vertebral syndesmophytes
- FBC - normocytic anaemia
- raised ESR/CRP
- HLA B27 positive
Treatment of ankylosing spondylitis
- exercise
- NSAIDs
- Infliximab - TNF alpha blocker
- local steroid injections
- bisphosphonates - alendronate
- hip replacement
Psoriatic arthritis
occurs in 10-40% of psoriasis patients
- mostly affects DIP joint
- symmetrical polyarthritis
Presentation of psoriatic arthritis
- nail changes, synovitis, acneiform rashes, palmoplantar pustulosis
- radiology - erosive changes, ‘pencil in cup’ deformity
Treatment of psoriatic arthritis
- NSAIDs
- infliximab
- methotrexate
What is reactive arthritis?
arthritis that occurs within 1 month of an infection elsewhere in the body
- usually related to a GU infection with chlamydia or GI infection with shigella, salmonella or campylobacter
Clinical presentation of reactive arthritis
- stiffness and pain in lower limb, asymmetric pattern with urethritis
- Reiter’s triad = urethritis, arthritis, conjunctivitis
Diagnostic tests in psoriatic arthritis
- Raised ESR/CRP
- culture stool if diarrhoea
- XR - enthesitis with periosteal reduction
Treatment of psoriatic arthritis
- NSAIDs/steroid injections
- methotrexate
What is septic arthritis?
joint inflammation caused by a microbe
- all joints get infected
CAN COMPLETELY DESTROY A JOINT WITHIN DAYS
How can bacteria enter a joint?
- pre-existing infection
- haematogenous spread
- contiguous spread = infection spreads from one area to another
Pathophysiology of septic arthritis
- Bacteria have PAMPs and these initiate an immune response
- inflammatory response occurs - joint becomes red, swollen and warm
- fluids accumulate in joint space - increased intra-articular pressure –> compressed blood vessels –> necrosis of affected bones and cartilage
Clinical presentation of septic arthritis
- differ according to underlying pathogen
- joint pain
- impaired range of movement
- fever
- Neisseria gonorrhoeae = haematological spread –> affects multiple joints and tenosynovitis
Aetiology of septic arthritis
- majority = non-gonococcal arthritis - staph aureus
- minority = gonococcal arthritis - Neisseria gonorrhoeae
Diagnosis of septic arthritis
- joint aspiration - MC&S of synovial fluid, high WCC, positive gram stain
- XR, US, CT, MRI - bone erosion and joint effusion
Treatment of septic arthritis
- antibiotics
- analgesics
- joint aspiration - arthrocentesis
- surgical operation - arthrotomy
What is osteomyelitis?
inflammation of the bone or bone marrow due to an infection
Cortical bone structure
contains osteons which have an empty centre - Haversian canals - contain blood vessels and nerves
Aetiology of osteomyelitis
- staph aureus
- salmonella - particularly affects individuals with sickle cell disease
Pathophysiology of osteomyelitis
- bacteria proliferates at bone
- immune response
- acute myelitis can be resolved –> osteoblasts and osteoclasts can repair the damage if the lesion is not extensive
- chronic –> affected bone becomes necrotic and separates from healthy bone = SEQUESTRUM –> osteoblasts may form new bone which wraps around the sequestrum = INVOLUCRUM
- inflammation may involve periosteum - can separate and allow abscess to form between
- infection can spread to a nearby joint
Clinical presentation of osteomyelitis
Acute osteomyelitis
- pain at site of infection
- fever
- may affect use of bone
Chronic osteomyelitis
- prolonged fever
- weight loss
Diagnosis of osteomyelitis
- FBC - high WCC, ESR, CRP
- XR - thickening of cortical bone and periosteum, elevation of periosteum, loss of trabeculae architecture, osteopenia
- MRI - identifies abscess
- bone biopsy - find pathogen responsible and confirm diagnosis
Treatment of osteomyelitis
- antibiotics
- abscess - surgery
- surgery to remove any necrotic bone (sequestrum)
What is SLE?
Autoimmune disease that affects a wide variety of organs and causes red lesions on the skin
Lupus is characterised by periods of flare ups and remittance
Pathogenesis of SLE
- environmental trigger (e.g. UV) damages cells and causes apoptosis
- genetic component means that susceptible individuals have certain genes that mean that cell debris is not effectively cleared –> lots of nuclear antigens
- immune response against nuclear antigens
- antigen-antibody complexes are deposited in numerous tissues (T3 hypersensitivity) –> this leads to an inflammatory response
- antibodies can also be made against erythrocytes and leukocytes (T2 hypersensitivity)
Clinical presentation of SLE
Classic presentation = fever, rash, joint pain in women of child-bearing age
- weight loss
- specific = depends on affected organs/tissues
Diagnosis of SLE
4 or more of 11 criteria
- malar rash - butterfly rash
- discoid rash
- ulcers in mouth and nose
- serositis - pericarditis, pleuritis
- arthritis - >2 joints
- renal disorders
- neurological disorders - seizures
- haematological disorders - cytopenia
- anti-nuclear antibodies (not specific as seen in other autoimmune conditions)
Treatment of SLE
- prevent flare ups and limit the severity of flare ups
- avoid sunlight exposure
- corticosteroids - limits immune response
- immunosuppressants
What is the difference between primary bone tumours and secondary bone tumours?
- primary = arise from bone cells
- secondary = metastasise from somewhere else and spread to bone (source = breast, prostate, thyroid, lung, kidneys)
Parts of bone (top to bottom)
- Epiphysis
- Metaphysis (contains growth plates)
- Diaphysis (bone shaft)
What do proto-oncogenes do?
promote normal cell growth
What do oncogenes do?
overstimulate cell growth
What do tumour suppressor genes do?
promote apoptosis
Give examples of benign bone tumours
- osteochondroma
- giant cell tumour of bone
- osteoblastoma (large nidus)
- osteoid osteoma (small nidus)
Give examples of malignant bone tumours
- osteosarcoma
- chondrosarcoma
Clinical presentation of bone tumours
- bone pain, fractures, swelling
- can cause numbness due to pressure on nerve
- malignant tumours –> chronic inflammatory response = fever, night sweats, weight loss, pulmonary symptoms (can metastasize to lungs)
Diagnosis of bone tumours
- Imaging = XR, CT, MRI - osteochondroma=exostosis, giant cell tumour=soap bubbles (multicystic bone lesions), osteosarcoma=lytic bone lesions-sunburst appearance
- testing for serum markers
Treatment of bone tumours
- depends on whether they are benign or malignant
- benign = surgically removed
- malignant = radiotherapy, chemotherapy, surgery
What is Paget’s disease
disorder where there is a lot of bone remodelling - excessive bone resorption and growth –> skeletal deformities and potential fractures
What do osteoblasts secrete?
- osteoid
- RANK-L
- OPG - osteoprotegerin (binds to RANKL and stops it binding)
Etiology of Paget’s diseaes
- unknown
- infection - measles virus
- genetic mutations - SQSTM1
Phases of disease in Paget’s
- lytic phase = osteoclasts aggressively demineralise bone
- mixed phase = lytic and blastic phase - rapid proliferation of new bone tissue by osteoblasts - collagen deposited in a haphazard way
- sclerotic phase = new bone formation exceeds bone resorption - disorganised and weaker bone
Clinical presentation of Paget’s disease
- typically no symptoms early on
- misshapen bones can impinge nerves and cause pain
- overgrowth of skull –> leontasis (lion-face), hearing and vision loss
- Kyphosis
- lower limb muscle weakness
- Pelvic asymmetry
- Bowlegs
- arthritis
- osteosarcoma –> Paget’s sarcoma
Diagnosis of Paget’s disease
- high alkaline phosphatase, calcium and phosphate normal
- XR - lytic lesions - thickened bone cortices
- Bone biopsy - excludes malignancy
Treatment of Paget’s disease
- pain relief
- antiresorptive medications = bisphosphonates
- surgery - correct bone deformities, decompress impinged nerves, reduce fractures
What is Sjogren’s syndrome?
autoimmune destruction of exocrine glands
