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Year 2 - LCRS > Musculoskeletal > Flashcards

Musculoskeletal Flashcards

1
Q

What prompts osteoprogenitor cells to become osteoclasts?

A

RANKL binding to RANK

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2
Q

What in inhibits RANK

A

OPG (Osteoprotegerin)

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3
Q

List the key features of rheumatoid arthritis

A

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)
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4
Q

Define rheumatoid factor

A

Antibodies that recognize the Fc portion of IgG as their target antigen typically IgM antibodies i.e. IgM anti-IgG antibody

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5
Q

What substance makes synovial fluid viscous?

A

Hyaluronic acid a non-sulphated glycosaminoglycan

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6
Q

Define Reactive Arthritis

A

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
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7
Q

List two infections associated with Reactive Arthritis

A

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)

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8
Q

Define and give two examples of an enthesopathy

A

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
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9
Q

What is the HLA association of Rehumatoid arthritis

A

HLA-DR4

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10
Q

What is the HLA association of Reactive arthritis

A

HLA-B27

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11
Q

Summarise osteoarthritis

A

Irreversible loss of articular cartilage, Mechanical in aetiology, mainly in the ageing population

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12
Q

Define (i) proteoglycan and (ii) glycosaminoglycan and give one example of each

A

Proteoglycan: glycoproteins containing sulphated glycosaminoglycan chains e.g.

•Aggrecan

Glycosaminoglycan repeating polymers of disaccharides e.g.

•Chondroitin sulphate

•Keratan sulphate

•Hyaluronic acid (= hyaluronate)

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13
Q

What is the major collagen found in articular cartilage?

A

Type II collagen

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14
Q

What is the major proteoglycan found in articular cartilage?

A

(i)Aggrecan

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15
Q

What is an osteophyte and name a condition in which they may be seen

A

Osteophytes, commonly referred to as bone spurs[1] are bony projections that form along joint margins.

Osteoarthritis (eg Heberden’s nodes)

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16
Q

What is the major HLA association for SLE?

A

HLA- DR3

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17
Q

Summarise the composition of bone

A

Bone is comprised of protein matrix (osteoid) and mineral (hydroxyapatite)

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18
Q

Define osteoporosis

A

Predisposition to skeletal fractures resulting from reduction in regional or total bone mass.

Bone chemistry is normal (serum calcium, phosphate, PTH, alkaline phosphatase)

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19
Q

What does a T-score calculate?

A

How many standard deviations the patient’s score is above/below the mean for a young, normal subject’s, representing ‘peak bone mass’

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20
Q

What are the paramenters for the following conditions?

A
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21
Q

Define osteomalacia

A

Osteomalacia literally means ‘soft bones’ and is defined as impaired mineralisation in mature bones. Rickets is impaired mineralisation in immature bones

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22
Q

What are the causes of osteomalacia ?

A

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)
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23
Q

What are the biochemical features of osteomalacia

A
  • 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
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25
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**
26
What bone chemistry is associated with Paget's disease?
High alkaline phosphatase
27
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
28
What are Codfish vertebrae and which condition are they associated with?
Biconcave deformity of vertebrae  Seen in  Osteoporosis Osteomalacia
29
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
30
What os trabecular bone?
Thin bone, in the marrow. High surface area. Metabollically active.
31
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
32
What might be the symptoms of hyperparathyroidism?
Stones Bones Abdominal groans psychic moans
33
Define arthritis
Arthritis – definite inflammation of a joint(s)
34
Define arthralgia
Arthralgia – pain within a joint without demonstrable inflammation by physical examination
35
What is lamellar bone
= mature bone composed of parallel lamellae or concentric lamellae
36
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.
37
As well as reumatoid factor, which other antibody might be present in rheumatoid arthritis?
CCP (Anti-cyclic citrullinated)
38
What is this and with which condition is it associated?
Swan-neck deformity. Rheumatoid arthritis
39
What is this and with which condition is it associated?
Boutonniere's deformty . Rheumatoid arthritis
40
What is this called and with which condition is it associated?
Heberden's nodes - osteoarthritis
41
What pro-inflammatory citokines are associated with rheumatoid arthritis ?
**TNF-Alpha** Il-1, Il-6
42
What drug class might prevent joint damage in RA and name one
DMARD (Disease Modifying Anit-Rheumatic Drugs) eg Methortrexate
43
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.
44
What is this called and with which condition is it associated?
Bouchard's nodes (PIP joint) - osteoarthritis
45
What does DMARDS stand for ? and give examples
Disease modifying antirheumatic drug Methotrexate Sulphasalazine Hydroxychloroquine
46
What are theseronegative spondyloarthropathies?
Reactive arthritis Ankylosing spondylitis Psoriatic arthritis
47
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.
48
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
49
50
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...
51
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
52
How do you assess whether SLE is active disease?
* Increased complement consumption = active disease. * Increased ESR * Increased anti-dsDNA ab's ## Footnote **\*ANA(antinuclear antibodies) and CRP are _NOT_ good indicators of disease activity**
53
How do you assess disease severity in SLE?
1. Identify pattern of organ involvement 2. Monitor function of affected organs - **Renal**- BP, U&E, urine sediment + Prot:Crea ratio - **Lungs/CVS**- Lung function, echocardiography - **Skin, haematology, eyes** 3. Identify pattern of autoantibodies expressed - Anti-dsDNA, anti-Sm (a nuclear antigen) - renal disease
54
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)
55
What is the treatment for mild SLE?
1. Paracetamol ± NSAIDs - Monitor renal function 2. Hydroxychloroquine - Arthropathy - Cutaneous manifestations - Mild disease activity 3. Topical corticosteroids
56
What is the treatment for moderate SLE?
Corticosteroids: - High initial dose to suppress disease activity Indication: - Failure of hydroxychloroquine/NSAIDs - Organ/life threatening disease
57
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
58
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)
59
What would you see on a characteristic SLE blood film ?
Schistocytes (Haemolytic component) Sherocytes Eliptocytosis Anisocytosis Thrombocytopaenia Fibrin Strands

Year 2 - LCRS (9 decks)

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