Musculoskeletal Flashcards
What prompts osteoprogenitor cells to become osteoclasts?
RANKL binding to RANK
What in inhibits RANK
OPG (Osteoprotegerin)
List the key features of rheumatoid arthritis
Chronic autoimmune disease characterised by pain, stiffness and SYMMETRICAL SYNOVITIS of synovial joints
- Morning stiffness in and around joints
- Symmetrical polyarthritis typically involving the small joints of the hand and/or wrists
- Subcutaneous nodules
- Rheumatoid factor
- The synovial membrane becomes thickened and chronically inflamed. Joint erosions of adjacent cartilage and bone (seen on radiographs)
Define rheumatoid factor
Antibodies that recognize the Fc portion of IgG as their target antigen typically IgM antibodies i.e. IgM anti-IgG antibody
What substance makes synovial fluid viscous?
Hyaluronic acid a non-sulphated glycosaminoglycan
Define Reactive Arthritis
Sterile inflammatory synovitis following an infection whose extra-articular manifestations may include:
- Enthesopathy
- Skin inflammation (circinate balanitis, keratoderma blennorrhagicum)
- Eye inflammation (conjunctivitis)
- HLA-B27 association
List two infections associated with Reactive Arthritis
Classically Gut and urogenitary
Urogenital infections
•E.g. Chlamydia trachomatis
Enterogenic infections
•E.g. Salmonella, Shigella, Campylobacter infections
(Reactive arthritis may be first manifestation of HIV or hepatitis C infection)
Define and give two examples of an enthesopathy
Inflammation where a ligament, tendon, fascia or capsule insert into bone. Examples include:
- Achilles tendonitis (painful heel)•
- Plantar fasciitis (painful feet)
- Spondylitis (spinal inflammation) in Ankylosing Spondylitis
- inflammation where the outer part (annulus fibrosis) of the inter-vertebral disc inserts into the vertebral body
What is the HLA association of Rehumatoid arthritis
HLA-DR4
What is the HLA association of Reactive arthritis
HLA-B27
Summarise osteoarthritis
Irreversible loss of articular cartilage, Mechanical in aetiology, mainly in the ageing population
Define (i) proteoglycan and (ii) glycosaminoglycan and give one example of each
Proteoglycan: glycoproteins containing sulphated glycosaminoglycan chains e.g.
•Aggrecan
Glycosaminoglycan repeating polymers of disaccharides e.g.
•Chondroitin sulphate
•Keratan sulphate
•Hyaluronic acid (= hyaluronate)
What is the major collagen found in articular cartilage?
Type II collagen
What is the major proteoglycan found in articular cartilage?
(i)Aggrecan
What is an osteophyte and name a condition in which they may be seen
Osteophytes, commonly referred to as bone spurs[1] are bony projections that form along joint margins.
Osteoarthritis (eg Heberden’s nodes)
What is the major HLA association for SLE?
HLA- DR3
Summarise the composition of bone
Bone is comprised of protein matrix (osteoid) and mineral (hydroxyapatite)
Define osteoporosis
Predisposition to skeletal fractures resulting from reduction in regional or total bone mass.
Bone chemistry is normal (serum calcium, phosphate, PTH, alkaline phosphatase)
What does a T-score calculate?
How many standard deviations the patient’s score is above/below the mean for a young, normal subject’s, representing ‘peak bone mass’
What are the paramenters for the following conditions?
Define osteomalacia
Osteomalacia literally means ‘soft bones’ and is defined as impaired mineralisation in mature bones. Rickets is impaired mineralisation in immature bones
What are the causes of osteomalacia ?
Due to inadequate phosphate and/or calcium
Caused by:
- Vitamin D deficiency
- Abnormal vitamin D metabolism e.g. liver or kidney disease
- Hypophosphataemia (may be due to renal phosphate loss which can be determined by measuring urinary phosphate levels)
What are the biochemical features of osteomalacia
- Low or normal serum calcium
- Low phosphate (PTH drives out phosphate throught the kidneys)
- Secondary hyperparathyroidism i.e. high PTH and high serum alkaline phosphatase
Define Paget’s disease
Disorder of bone remodelling of unknown cause where there is increased bone resorption followed by increased bone formation. This results in disorganised mosaic pattern of woven and lamellar bone.
Leads to bone pain and fractures
Causes increased bone thickness
What bone chemistry is associated with Paget’s disease?
High alkaline phosphatase
What are Looser’s zones and which condition are they associated with?
Osteomalacia
Pseudo/insufficiency fractures at high tensile stress areas as a result of too much un-mineralised osteoid
- Medial proximal femur
- Lateral scapula
- pubic rami
- posterior proximal ulna
- ribs
What are Codfish vertebrae and which condition are they associated with?
Biconcave deformity of vertebrae
Seen in
Osteoporosis
Osteomalacia
What is a brown tumour?
Brown tumors are a bone lesion that arises in settings of excess osteoclast activity, such as hyperparathyroidism.
Consist of fibrous tissue, woven bone and supporting vasculature, but no matrix
What os trabecular bone?
Thin bone, in the marrow. High surface area. Metabollically active.
Which 3 organs might be responsible for Ca deficiency?
GI tract - Malabsorption
Kidney - Vit D activation 1,25enables Ca absorption
Liver - Cannot hydroxylate Vit D
What might be the symptoms of hyperparathyroidism?
Stones
Bones
Abdominal groans
psychic moans
Define arthritis
Arthritis – definite inflammation of a joint(s)
Define arthralgia
Arthralgia – pain within a joint without demonstrable inflammation by physical examination
What is lamellar bone
= mature bone composed of parallel lamellae or concentric lamellae
What is the composition + classification of bone?
Composition: INORGANIC (65%) = Consists of calcium hydroxyapatite, Stores 99% of total body calcium; ORGANIC (35%) = Bone cells and protein matrix.
As well as reumatoid factor, which other antibody might be present in rheumatoid arthritis?
CCP (Anti-cyclic citrullinated)
What is this and with which condition is it associated?
Swan-neck deformity. Rheumatoid arthritis
What is this and with which condition is it associated?
Boutonniere’s deformty . Rheumatoid arthritis
What is this called and with which condition is it associated?
Heberden’s nodes - osteoarthritis
What pro-inflammatory citokines are associated with rheumatoid arthritis ?
TNF-Alpha Il-1, Il-6
What drug class might prevent joint damage in RA and name one
DMARD (Disease Modifying Anit-Rheumatic Drugs)
eg Methortrexate
AS well as DMARDS what other treatments for RA might be investigated?
Biological Therapy
Monoclonal antibodies eg Anti-TNF-alpha (but TNF-alpha important to protect against TB)
Glucocorticoid therapy short term.
What is this called and with which condition is it associated?
Bouchard’s nodes (PIP joint) - osteoarthritis
What does DMARDS stand for ? and give examples
Disease modifying antirheumatic drug
Methotrexate
Sulphasalazine
Hydroxychloroquine
What are theseronegative spondyloarthropathies?
Reactive arthritis
Ankylosing spondylitis
Psoriatic arthritis
What is SLE and what might be the presenting symptoms?
One of a family of overlapping autoimmune diseases. Systemic disease.
Presents with: Fever, Malaise, fatigue, lymphadenopathy, arthralgia, Raynaud’s phenomenon and a characteristic malar rash.
What monoclonal antibody acts against RANKL? What is this used to treat?
Denosumab
- Indicated for treatment of osteoporosis, bone metastases, multiple myeloma and Giant cell tumours
Describe the pathophysiology of SLE
Abnormal clearance of apoptotic cell material
↓
Dendritic cell uptake of autoantigens and activation of B cells
↓
B cell Ig class switching and affinity mutation
↓
IgG autoantibodies
↓
Immune complexes
↓
Complement activation, cytokine generation…
What are the laboratory tests for SLE?
Anti-nuclear antibodies:
ANA relatively non-specific, pattern important
Anti-dsDNA and Sm antibodies
More specific but less sensitive
How do you assess whether SLE is active disease?
- Increased complement consumption = active disease.
- Increased ESR
- Increased anti-dsDNA ab’s
*ANA(antinuclear antibodies) and CRP are NOT good indicators of disease activity
How do you assess disease severity in SLE?
- Identify pattern of organ involvement
- Monitor function of affected organs
- Renal- BP, U&E, urine sediment + Prot:Crea ratio
- Lungs/CVS- Lung function, echocardiography
- Skin, haematology, eyes - Identify pattern of autoantibodies expressed
- Anti-dsDNA, anti-Sm (a nuclear antigen)
- renal disease
How would you categories SLE patients into Mild, Moderate, Severe?
Mild ->Joint ± skin involvement
Moderate -> Inflammation of other organs;
- pleuritis
- pericarditis
- mild nephritis
Severe ->Severe inflammation in vital organs:
- Severe nephritis
- CNS disease
- Pulmonary disease
- Cardiac involvement
- AIHA, thrombocytopaenia, TTP (thrombotic thrombocytopaenic Purpura)
What is the treatment for mild SLE?
- Paracetamol ± NSAIDs
- Monitor renal function - Hydroxychloroquine
- Arthropathy
- Cutaneous manifestations
- Mild disease activity - Topical corticosteroids
What is the treatment for moderate SLE?
Corticosteroids:
- High initial dose to suppress disease activity
Indication:
- Failure of hydroxychloroquine/NSAIDs
- Organ/life threatening disease
What is the treatment for severe SLE?
Azathioprine:
- Effective steroid sparing agent
- 20% neutropenia
- Regular FBC and biochemistry monitoring
Cyclophosphamide
- Severe organ involvement, I.V. pulsed or oral treatment
- Risk of infertility
What is the bimodal mortality pattern of SLE?
There is an early peek in mortality and then later a 2nd peak due to:
- *Early:**
- Renal failure
- CNS disease
- Infection
- *Late:**
- Myocardial infarction, stroke (SLE patients = increase atherosclerotic risk in 4th/5th decade)
What would you see on a characteristic SLE blood film ?
Schistocytes (Haemolytic component)
Sherocytes
Eliptocytosis
Anisocytosis
Thrombocytopaenia
Fibrin Strands
