Muskuloskeletal Flashcards
(172 cards)
1
Q
What is metabolic bone disease?
A
A group of diseases that cause a decrease in bone density and bone strength by:
1) Increasing bone resorption
2) Decreasing bone formation
- May be associated with disturbances in mineral metabolism
2
Q
Give examples of metabolic bone diseases?
A
- Primary hyperparathyroidism
- Rickets/Osteomalacia
- Osteoporosis
- Paget’s disease
- Renal osteodystrophy
3
Q
What are the symptoms of metabolic bone diseases?
A
Metabolic: Hypocalcaemia, hypercalcaemia, hypo/hyperphosphataemia Bone: Deformity, Fractures
4
Q
How is calcium stored in the bone?
A
- Inorganic hydroxyapatite
5
Q
What are the factors that contribute to bone strength?
A
Quantity: - Cortical thickness - Mineral density - Size Quality - Architecture - Bone turnover - Cortical porosity - Trabecular connectivity
6
Q
How can bone structure and function be assessed?
A
- Bone histology
- Biochemical tests
- Bone mineral densitometry e.g. osteoporosis
- Radiology e.g. osteomalacia, Paget’s disease
7
Q
What are the serum features investigated in metabolic bone disease?
A
Calcium, corrected calcium, albumin, phosphate, parathyroid hormone, 25-hydroxy vitamin D
8
Q
What are the urine features investigated in metabolic bone disease?
A
NTX
Calcium
Phosphate
9
Q
Where does absorption of calcium occur?
A
Jejunum and ileum
Passive or active (vit D controlled)
10
Q
What is the total serum calcium?
A
2.15-2.56 mmol/L
11
Q
What is the role of PTH in plasma calcium regulation?
A
- Predominant role in minute by minute regulation
- Afferent-limb sensing
- If calcium drops, within seconds there is secretion of PTH from pre-formed stores
- Acts on bone and kidney
12
Q
What is the affect of PTH on the bone?
A
- Increased resorption
- Release of Ca++ and phoshphate
13
Q
What is the affect of PTH on the kidney?
A
- Increased phosphate excretion
- Increased calcium reabsorption
- Increased calcitorol formation leading to increased intestinal CaH04 absorption
14
Q
What does serum calcium consist of?
A
46% protein-bound
47% ionised
7% complexes
15
Q
What is the calcium sensing receptor?
A
Links serum calcium to the PTH gland
16
Q
How does PTH release calcium from the bone?
A
- Activates the RANK system
- Osteoblast has rank ligand on its membrane, interacts with macrophages which stimulate osteoclasts
17
Q
Where does PTH activate vitamin D in the kidney?
A
In the proximal tubule of the kidney
18
Q
Where does PTH increase calcium re-absorption in the kidney?
A
Distal tubule of the kidney
19
Q
Where does PTH decrease phosphate re-absorption in the kidney??
A
Proximal tubule
20
Q
What are the causes of primary hyperparathyroidism?
A
- Parathyroid adenoma
- Parathyroid hyperplasia
- Parathyroid CA
- Familial syndroms (MEN 1, MEN 2A)
21
Q
What is the biochemistry of primary hyperparathyroidism?
A
- Increased serum calcium by absorption from bone/gut/kidney
- Decreased serum P04, increased absorption is overcome by marked renal excretion
- Increased urine calcium excretion as increased renal resorption is overcome by the hugely increased filtered load
- Increased markers of bone resorption
22
Q
What are the clinical features of primary hyperparathyroidism?
A
- Mainly due to high calcium: thirst, polyuria, tiredness, fatigue, muscle weakness
‘Stones, abdominal moans and psychic groans’ - Renal colic, nephrocalcinosis, CRF
- Dyspepsia, pancreatitis
- Constipation, nausea, anorexia
- Depression, impaired concentration
- Drowsy, coma
23
Q
How is primary hyperparathyroidism managed?
A
- Depends on age and severity
- Very young or high calcium patients have a huge risk of developing complications such as osteoporosis, renal stone and renal failure therefore surgery is necessary
- Other management is conservative, focuses on preventing complications using bisphospnoates and calcimemetics
24
Q
What is osteomalacia?
A
Inadequate vitamin D activity which leads to defective mineralisation of the cartilaginous growth plate (before a low calcium)
25
What are the symptoms of osteomalacia?
- Bone pain and tenderness (axial)
- Muscle weakness (proximal)
- Lack of play
26
What are the signs of osteomalacia?
- Age dependent deformity
- Myopathy
- Hypotonia
- Short stature
- Tenderness of percussion
27
What are the causes of osteomalacia?
- Vitamin D related which may be dietary
- Gastrointestinal: Small bowel malabsorption, bypass, Pancreatic insufficiency, Liver/biliary disturbance,
Drugs: phenytoin, phenobarbitone
- Renal: chronic renal failure, vitamin D dependent rickets type I, autosomal recessive, no 1a hydroxylation
- Resistance: vitamin D dependent rickets type II, autosome recessive
28
What is the biochemistry of osteomalacia?
```
Calcium= N/low
Phosphate= N/low
Alkaline phosphate= High
PTH= High
Urine phosphate= high
-Glycosuria, aminoaciduria, high pH and proteinuria
```
29
How does osteomalacia relate to phosphate?
Can get osteomalacia with renal phosphate loss, when calcium and Vitamin D levels are usually normal
30
How does oestrogen deficiency affect bone?
1) Increases the activation frequency of remodelling units (number of osteoblasts and blasts)
2) Causes remodelling imbalance
- Decreases osteoclast apoptosis apoptosis, increases osteoblast apoptosis
- Deeper and more resorption pits
- Increased bone resorption compared to bone formation
3) Remodelling errors
- Trabecular perforation
- Cortical excess Haversian excavation
4) Decreased osteocyte sensing
31
What are the causes of osteoporosis due to high turnover?
Increased bone resorption greater than bone formation
- Oestrogen deficiency- primarily in postmenopausal women
- Hyperparathyoidism
- Hyperthyroidism
- Hypogonadism in young women and in men
- Heparin
32
What are the causes of osteoporosis due to low turnover?
Decrease bone formation more pronounced than decreased bone resorption
- Liver disease- primarily primary biliary cirrhosis
- Heparin
- Age above 50
33
What are the causes of osteoporosis due to increased bone resorption and decrease bone formation?
Glucocorticoids
34
What is the biochemistry of osteoporosis?
Should be normal but check for vit D deficiency and secondary endocrine causes
- Exclude multiple myeloma
35
Why should bone density be measured?
Single best predictor of fracture risk BMD represents 70% of total risk
36
What is DXA?
Dual energy X-ray absorptiometry
- Measureres transmission through the body of X-rays of two different photon energies
- Enables densities of two different tissues to be inferred i.e. bone mineral, soft tissue
37
How is osteoporosis defined by T-score?
Measured BMD- young adult mean BMD
| /young adult standard deviation
38
What situations interfere with vertebral measurement interpretations?
- Degenerative change, osteoarthritis
- Vertebral fractures
- Metal artefacts
- Osteomalacia
- Vascular calcification
- Scoliosis
- Paget's disease
39
How is collagen synthesised for bone formation?
Alpha 1 and 2 chains of type I collagen produced by osteoblast
- Proline and lysine residues hydroxylated
- 3 hydroxylysine molecules on adjacent tropocollagen fibrils condense to form a pyridinum ring linkage
- Collagen breakdown products are good markers of bone resorption as they are directly linked to the amount of bone resorbed
40
How is osteoclast activity measures?
By measuring urine hydroxyproline or urine-collagen cross-links
41
What are markers of bon resorption?
Serum CTX
NTX
Tartrate resistant acid phosphatase
42
What is bone specific alkaline phosphate? (BSAP_
- Tissue specific form: liver vs bone, intestine, germ cell, placental forms
- Essential for mineralisation, regulates concentrations of phosphocompounds
- Increased in Paget's disease osteomalacia, bone metastases, hyperparathyroidism, hyperthyroidism
43
What is tertiary hyperparathyroidism?
- Due to chronic renal impairment
- Nephron loss> reduce production of active calcitrol
- Reduced vit d levels leads to osteomalacia
- Deceased calcitrol leads to hypoacalcaemia, secondary PTH increase, increased bone resportion
- Nephron loss leads to phosphate retendtion causing hyperphosphataemia, leading to metastatic calcification
- Nephron loss causes acidosis which causes demineralisation contributing to osteoporosis
44
What is the function of bone?
- Mechanical: support and site for muscle attachment
- Protective: vital organs and bone marrow
- Metabolic: reserve of calcium
45
What is the composition of bone?
- INORGANIC - 65%
– calcium hydroxyapatite (10Ca 6PO4 OH2) – is storehouse for 99% of Ca in the body
– 85% of the phosphorous, 65% Na & Mg
- ORGANIC - 35%
– bone cells and protein matrix
46
How is bone classified?
```
Cortical:
Long bones, 80% of skeleton, appendicular, 80-90% calcified, mainly mechanical and protective
Cancellous:
- Vertebrae & pelvis, 20% of skeleton
- Axial
- 15-25% calcified
- Mainly metabolic
- Large surface
```
47
What are the indications for use of bone biopsy?
- Investigating an abnormality seen on an x-ray
- Evaluate bone pain or tenderness
- Bone tumour diagnosis (benign vs malignant)
- Determining the cause of unexplained infection
- Evaluating the progress of therapy
48
What are the types of bone biopsies?
- Close: used most commonly as poses smallest risk
| - Open: for sclerotic or inaccessible lesions
49
What are the different bone cells?
- Osteoblasts: build bone by laying down osteoid
- Osteoclasts: multinucleate cells of macrophage family resorb or chew bone
- Osteocytes: osteoblast like cells which sit in the lacunae in bone
50
What is RANK?
Receptor activator for nuclear factor kB
51
What is OPG?
Osteoprotegerin-
| Inhibits RANK/RANKL binding therefore inhibiting osteoclastogenesis
52
How are types of bone classified anatomically?
1) Anatomically- flat/long/cuboid bones
- Intramembranous ossification (flat) and endochrondral ossification (long)
2) Trabecular bone (cancellous)
3) Compact bone (cortical)
4) Women bone (immature)
5) Lamellar bone (mature)
53
What is metabolic bone disease?
- Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, mienrals)
- Overall effect is reduced bone mass (osteopaenia) which often results in fracture with little or no trauma
54
What are the 3 main categories of metabolic bone disease?
1) Related to endocrine abnormality (Vit D; Parathyroid hormone)
2) Non-endocrine (e.g. related osteoporosis)
3) Disuse osteopaenia
55
What is osteomalacia?
Defective bone mineralisation
Types:
1) Deficiency of vitamin D
2) Deficiency of P04
56
What is the mechanism of osteomalacia?
- Vitamin D plays integral role in calcium metabolism
- Vit D deficiency results in increased PTH and subsequent increase bone resorption
- Vit D deficiency also cause hypocalcaemia
57
What are the effects of osteomalacia?
- Bone pain/tenderness
- Fracture
- Proximal weakness
- Bone deformity
58
What is hyperparathyroidism?
Excess PTH
- Increased Ca + P04 excretion in urine
- Hypophosphataemia
- Skeletal changes of osteitis fibrosa cystica
59
Which 4 organs are directly or indirectly affected by PTH and between them control Ca metabolism?
- Parathyroid glands
- Bones
- Kidneys
- Proximal small intestine
60
What are the difference between primary and secondary hyperparathyroidism?
```
Primary:
- Parathyroid adenoma
- Chief cell hyperplasia
Secondary:
- Chronic renal deficiency
- Vit D deficiency
```
61
What is renal osteodystrophy?
Results from from chronic renal disease. Comprises all skeletal change of chronic renal disease:
1. Increased bone resorption (osteitis fibrosa cystica)
2. Osteomalacia
3. Osteosclerosis
4. Growth retardation
5. Osteoporosis
62
What are the symptoms of osteodystrophy?
- PO4 retention – hyperphosphataemia
- Hypocalcaemia as a result of ↓vit D
- Secondary hyperparathyroidism
- Metabolic acidosis
- Aluminium deposition
63
What is Paget's disease?
```
- Disorder of bone turnover
Divided into 3 stages
1) Osteolytic
2) Osteolytic-osteosclerotic
3) Quiescent osteosclerotic
```
64
What are the clinical symptoms of Paget's disease?
- Pain
- Microfractures
- Nerve compression
- Skull changes may put medulla at risk
- Deafness
- +/- haemodynamic changes, cardiac failure
- Hypercalcaemia
- Development of sarcoma in area of involvement
65
What is a Haversian canal?
Channel that the blood vessels run in the bone
66
What are Canaliculae?
Provide routes for cell communication
67
What is Howship's lacunae?
Pits in the bone surface in which osteoclasts are found, often called resorption bays
68
What is 'Codfish vertebra'?
In osteomalacia
- Biconcave loss of height
- Osteopenic
- Pencilled-in margin
69
What are the radiological features of osteomalacia?
- Less mineral
- Osteopenia
- Bend and bow be
fore break
- Codfish vertebrae
- Changes in mature bone
- Looser's zon's
70
What are the radiological features of osteoporosis?
- Osteopenia
- Break
- Anterior wedging
71
What are the radiological features of Ricket's?
- Indistinct frayed metaphyseal margin?
- Widened growth plate (no calcification)
- Cupping/splaying
- Rickety rosary - splayed and cupped anterior ends of ribs
- Osteopenia
72
What is rheumatoid arthritis?
- Chronic joint inflammation that can result in joint damage
- Site of inflammation is in the synovium
- Associated with antibodies: rheumatoid factor, anti-cyclic citrullinated peptide (CCP) antibodies
73
What is ankylosing spondylitis?
- Chronic spinal inflammation that can result in spinal fusion and deformity
- Site of inflammation is the enthesis
- No antibodies 'seronegative'
74
Give examples of seronegative spondyloarthropathies
- Ankylosing spondylitis
- Reiters syndrom and reactive arthritis
- Arthritis associated with psoriasis (psoriatic arthritis)
- Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
75
What is systemic lupus erythematosus (SLE)?
- Chronic tissue inflammation in the presence of antibodies directed against self-antigens
- Multi site inflammation but particularly the joints, skin and kidney
- Associate with autoantibodies: Antinuclear antibodies, anti-double stranded DNA antibodies
76
Give examples of connective tissue diseases
- Systemic lupus erythematous
- Inflammatory muscle disease: polmyositis, dermatomyositis
- Systemic sclerosis
- Sjogren's syndrome
- A mixture of the above: 'Overlap syndromes'
77
What HLA subtype is rheumatoid arthritis linked to?
HLA-DR4
| - HLA-DR4 triggers CD4+ T cell responses
78
What HLA subtype is Systemic Lupus Erythematosus linked to?
HLA-DR3
79
What HLA subtype is Ankylosing Spondylitis linked to?
HLA- B27
| - HLA-B27 triggers CD8+ T cell responses
80
What are the levels of complements and anti-ds-DNA antibodies in SLE?
Low complement levels
| High serum lvels of anti-ds-DNA antibodies
81
What is the pathogenesis of SLE?
- Apoptosis leads to translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
82
What is the role of cytokines in rheumatology?
- TNFalpha is the dominant pro-inflammatory cytokine in rheumatoid synovium and its actions are detrimental in this setting
- We can target:
IL-2 antibodies in organ transplants
IL-6 in rheumatoid arthritis
TNF-alpha
83
What is the importance of RANKL in rheumatology?
RANKL is important in bone destruction in rheumatoid arthritis
- Acts to stimulate osteoclast formation
- Upregulated by: IL-1, TNFalpha, IL-17, PTH-related peptide
- Binds to ligand on osteoclast precursors- osteoprotegerin (OPG)
84
What is Denosumab?
Monoclonal antibody against RANKL
| - Indicated for treatment of osteoporosis, bone metastases, multiple myeloma and Giant cell tumours
85
What is the role of B cells in SLE?
B cell hyperreactivity is a key feature.
| - To treat SLE, biological therapies have been used with target B cells
86
Which drugs act against B cells to treat SLE?
Rituximab- chimeric anti-CD20 antibody used to deplete B cells
Belimumab- monoclonal antibody against a B cell survival factor called BLYS. Inhibits activity of BLYS resulting in impaired B cell survival and reduced B cell numbers
87
What are the key features of rheumatoid arthritis?
1) Chronic arthritis:
- Polyarthritis, swelling of the small joints of the hand and wrists
- Symmetrical
- Early morning stiffness in and around joints
- May lead to joint damage and destruction- 'joint' erosions on radiographs
2) Extra-articular disease
- Rheumatoid nodules
3) Rheumatoid 'factor' may be detected in blood
- IgM auoantibody against IgG
88
What environmental factor contributes to rheumatoid arthritis?
Smoking
89
What are the commonly affected joints in rheumatoid arthritis?
- Metacapophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
90
What is the primary site of pathology in rheumatoid arthritis?
```
Synovium
This includes
- Synovial joints
- Tenosynovium surrounding tendons
- Bursa
```
91
What are sub-cutaneous nodules?
```
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Associated with:
- Severe disease
- Extra-articular manifestations
- Rheumatoid factor
```
92
What is Rheumatoid factor?
- Antibodies that recognise the Fc portion of IgG as their target antigen
- Typically IgM antibodies
93
Why do antibodies to citrullinated protein antigens develop in rheumatoid arthritis?
- PADs present in high concs in neutrophils and monocytes, there is increased citullination of autogolous peptides in the inflamed synovium
- ACPA associated with smoking and HLA 'shared epitope'
- Shared epitope binds non-polar amino acids like citrulline but not positively charged ones like arginine.
94
What is citrullation of peptides mediated by?
Peptidul arginine deiminases (PADs)
| - Convert arginine to citrulline
95
What are the extra-articular features of rheumatoid arthritis?
Common: Fever, weight loss, subcutaneous nodules
Uncommon: vasculitis ocular inflammation, neuropathies, amyloidosis
96
What are the radiographic abnormalities of rheumatoid arthritis?
Early: Juxta-artciular osteopenia
Later: Joint erosions at margins of the joint
Later still: Joint deformity and destruction
97
What is the pathogenesis of rheumatoid arthritis?
Synovial membrane is abnormal in rheumatoid arthritis
Synovium becomes proliferated mass of tissue due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells (activated B and T cells, plasma cells, mast cells, activated macrophages
- Recruitment, activation and effector functions of these cells is controlled by a cytokine network
98
What are DMARDs
Disease Modifying Anti-Rheumatic Drugs
- Drugs that may induce remission (not cure) and prevent joint damage
Work by
- Reducing the amount of inflammation in the synovium
- Slow or prevent structural joint damage e.g. bone erosions
99
Give examples of DMARDs
```
Methotrexate
Sulphasalazine
Hydroxychloroquine
Leflunomide
Gold
Penicillamine
```
100
What are the problems with biological therapies for rheumatoid arthritis?
- TNFalpha inhibition is associated with increased susceptibility to mycobacterial infection
- B cell depletion therapy can be associated with hepatitis B reactivation
- B cell depletion therapy can be associated with JC virus infection and progressive multifocal leukoencephalopathy
101
What is reactive arthritis?
Sterile inflammation in joints following infection, especially urogenital and gastrointestinal infections
- May be first manifestation of HIV or heptatitis C infection
- Distinct from infection in joints (septic arthritis)
102
What are the extra-articular manifestations of arthritis?
- Enthesopathy
- Skin inflammation
- Eye inflammation
103
What are the arthritis symptoms of reactive arthirits?
- Joint inflammation and morning joint stiffness
- Patterns of joints involved can help distinguish from rheumatoid arthritis
- Asymmetrical oligoarthritis (
104
What are the enthesitis symptoms of reactive arthritis?
- Inflammation where a ligament, tendon, fascia or capsule insert the bone
- Heal pain (Achilles tendon), swollen fingers (dactylitis), Painful feet (metatarsalgia due to plantar fascilitis)
105
What are the spondylitis symptoms of reactive arthritis?
- Inflammation of the spine
- Patient may suffer sacroilitis- sacroiliac joint inflammation
- Spondylitis allows for exclusion of rheumatoid arthritis without any need for investigations
106
What are the extra-articular features of reactive arthritis?
- Ocular: Sterile conjuctivitis
- Genito-urinary: sterile urethritis
Skin- circinate balanitis, psoariasis-like rash on hands and feet
107
How does rheumatoid arthritis compare to reactive arthritis with regards to sex and age?
```
Rheumatoid arthritis:
F>M
All ages
Reactive arthritis:
M>F
20-40 years
```
108
What are the differences between the features of arthritis in rheumatoid and reactive arthritis?
Rheumatoid:
- Symmetrical, polyarticular, small & large joints
Reactive:
- Asymmetrical, Oligoarticular, Large joints
109
Is the enthesopathy, spongylitis and urethritis in rheumatoid arthritis and reactive arthritis?
Rheumatoid: None of the 3
Reactive: All 3
110
How is skin involved in rheumatoid and reactive arthritis?
Rheumatoid: Subcutaneous nodules
Reactive: K.blennorhagicum, Circinate balantis
111
What is the HLA association in rheumatoid and reactive arthritis?
Rheumatoid: HLA-DR4
Reactive: HLA-B27
112
How is diagnosis of reactive arthritis established?
- Clinical diagnosis
- Investigations to exclude other causes of arthritis e.g. septic arthritis
Investigations:
Microbiology: cultures, serology
Immunology: rheumatoid factor
Synovial fluid examination
113
What are the differences between septic and reactive arthritis?
```
- Septic arthritis:
Synovial fluid culture- positive
Antibiotic therapy- yes
Joint lavage- yes for large joints
- Reactive arthritis:
Synovial fluid culture- sterile
Antibiotic therapy- No
Joint lavage- no
```
114
How is reactive arthritis treated?
- Articular: NSAIDs, intra-articular corticosteroid therapy
- Extra-articular: Typically self limiting, hence symptomatic therapy e.g. topical steroids
- Refractory disease: oral glucocorticoids, steroid-sparing agents
115
What is osteoarthritis?
Chronic slowly progressive disorder due to failure of articular cartilage that typically affects joints of the hand, spine and weight-bearing joints
116
What is affected in osteoarthritis?
- Joints of the hand- distal interphalangeal joints (DIP), Proximal interphalangeal joints (PIP), First carpometacarpal joint (CMC)
- Spine
- Weight-bearing joints of lower limbs: esp. knees and hips, first metatarsophalageal joint (MTP)
117
What are osteophytes at DIP joints called?
Heberden's nodes
118
What are osteophytes at the PIP joints called?
Bouchard's nodes
119
What can osteoarthritis be associated with?
- Joint pain
- Joint crepitus (creaking, cracking grinding sound on moving affected joint)
- Joint instability
- Joint enlargement (e.g. Heberden's nodes)
- Joint stiffness after immobility
- Limitation of motion
120
What are the radiographical features of osteoarthritis?
- Joint space narrowing
- Subchondral bony sclerosis
- Osteophytes
- Subchondral cysts
121
How do radiographic changes in rheumatoid arthritis differ from Osteoarthritis?
```
Rheumatoid arthritis:
Joint space narrowing- YES
Subchondral sclerosis- NO
Osteophytes- NO
Osteopenia- YES
Bony erosions- YES
Osteoarthritis:
Joint space narrowing- YES
Subchondral sclerosis- YES
Osteophytes- YES
Osteopenia- NO
Bony erosions- NO
```
122
What causes the problems in osteoarthritis?
There is defective and irreversible articular cartilage and damage to the underlying bone
- Develops because of excessive loading on joints and/or abnormal joint components
123
What do the properties of articular cartilage depend on?
Weight bearing properties depend on intact collagen scaffold and high aggrecan content
124
What are the cartilage changes in osteoarthritis?
- Reduced proteoglycan
- Reduced collagen
- Chondrocyte changes e.g. apoptosis
125
What are the bone changes in osteoarthritis?
Changes in denuded sub-articular bone:
- Proliferation of superficial osteoblasts results in production of sclerotic bone e.g. subchondral sclerosis
- Focal stress on sclerotic bone can result in focal superficial necrosis
New bone formation at the joint margins (osteophytes):
126
How is osteoarthritis managed?
- Education
- Physical therapy
- OT
- Weight loss where appropriate
- Exercise
- Analgesia (paracetamol, NSAID, intra-articular corticosteroid inject)
- Joint replacement
127
How does SLE present?
- Malaise
- Fatigue
- Fever
- Weight loss
- Lymphadenopathy
128
What are the features of SLE?
```
Specific:
- Butterfly rash, alopecia
- Arthralgia
- Raynaud's phenomenon
Other:
- Inflammation of kidney, CNS, heart, lungs
- Accelerated atherosclerosis
- Vasculitis
```
129
What is the ACR criteria?
4 or more indicative of SLE
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis
- Renal disorder
- Neurological disorder
- Haematological disorder
- Immunological disorder
- Anitnuclear antibody in raised titre
130
What is the pathogenesis of SLE?
Regulation of B cell function is lose. Hyperactive B cells with a failure to clear apoptotic cells allow for the production of autoantibodies
131
How are autoantibodies formed?
- Abnormal clearance of apoptotic cell material
- Dendritic cell uptake of autantigens and activation of B cells
- B cell Ig class switching and affinity mutation
- IgG autoantibodies
- Immune complexes
- Complement activation, cytokine generation
132
What laboratory tests are available for SLE?
1) Antinuclear antibodies
2) Anti-dsDNA and Sm
3) Anti-Ro and/or La
4) Haematology
- Lymphopaenia
- Leukopaenia
5) Renal
- Proteinuria
- Active urinary sediment
133
How is the severity of SLE distinguished?
```
Mild: Joint and/or 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
```
134
How is mild SLE treated?
1) Paracetamol and/or NSAID
- Monitor renal function
2) Hydroxychloroquine
- Arthropathy
- Cutaneous manifestations
- Mild disease activity
3) Topical corticosteroids
135
How is moderate SLE treated?
Indicated by failure of hydroxychloroquine/NSAID with presentation of organ/life threatening disease
Corticosteroids:
- High initial dose to suppress activity
- IV methylprednisolone
136
How is severe SLE treated?
1) Azathioprine:
- Effective steroid-sparing agent
2) Clycophosphamide:
Used in nephritis
- Can cause BM suppression, infertility, cystitis
137
What is the bimodal mortality pattern of SLE?
In early disease of active lupus there is renal failure and CNS disease, as well as infection
- In later less active disease, these patients are at risk of myocardial infarction
138
What is the GALS examination?
The purpose is to see if any of the joints are abnormal
| Gait, Arms, Legs, Spine
139
How is gait observed in the GALS examination?
Observe the patient waking, turning and walking back. Look for:
- Smoothness and symmetry of leg, pelvis and arm movements
- Normal stride length
- Ability to turn quickly
140
How is the spine observed in the GALS examination?
- Is the paraspinal and shoulder girdle muscle bulk symmetrical
- Is the spine straight?
- Are the iliac crests level?
- Is the gluteals muscle bulk normal?
- Are there popliteal swellings?
- Are the Achilles tendons normal?
- Are the spinal curvatures normal?
- Is lumbar spine and hip flexion normal
- Is the cervical spine normal?
141
How are the arms observed in the GALS examination?
- Look for normal girdle muscle bulk and symmetry
- Look to see if there is full extension at the elbows
- Are shoulder joints normal
- Examine hands palms down with fingers straight
- Observe supination, pronation, grip and finger movements
- Test for synovitis at the metacarpo-phalangeal joints (MCP)
142
How are the legs observed in the GALS examination?
- Look for knee or foot deformity
- Assess flexion of hip and knee
- Look for knee swellings
- Test for synovitis at the metatarso-phalangeal joints
- Inspect soles of the feet
143
What does a detailed examination of any abnormal joints identified in the GALS screening include?
- Inspection: swelling, redness, deformity
- Palpitation: warmth, crepitus, tenderness
- Movement: active, passive, against resistance
- Function: loss of function
144
What are signs of inflammation?
- Swelling
- Warmth
- Eryhthma
- Tenderness
- Loss of function
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What is arthritis?
Refers to definite inflammation of joints i.e. swelling, tenderness and warmth of affected joints
146
What is arthralgia?
Refers to pain within joints without demonstrable inflammation by physical examination
147
What is dislocation?
Articulating surfaces are displaces and no longer in contact
148
What is subluxation?
Partial dislocation
149
What is varus deformity?
Lower limb deformity whereby the distal part is directed towards the midline
e.g. varus knee with medial compartment osteoarthritis
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What is valgus deformity?
Lower limb deformity whereby the distal part is directed away from the midline
e.g. hallux valgus
151
What is gout?
An example of arthritis
- Disease in which tissue deposition of monosodium urate (MSU) crystals occur as a result of hyperuricaemia and leads to one or more of the following
- Gouty arthritis
- Tophi (aggregated deposits of MSU in tissue)
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What is gouty arthritis?
Commonly affects the metatarsophalangeal joint of the big toe (1st MTP joint)
- Abrupt onset
- Extremely painful
- Joint red, warm, swollen and tender
- Resolves spontaneously over 3-10 days
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What is enthesopathy?
A non-articular soft tissue at the enthesis (the site where ligament or tendon inserts into bone
e.g. plantar fascilities and Achilles tendinitis
154
What is polyarthritis, olgioarthritis and monoarthritis?
```
Polyarthritis= >4 joints involved
Oligoarthritis= 2-4 joints involved
Monoarthritis= Single affected joint
```
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Why should the symmetry, size of involved joints and axial involvement of arthritis be noted?
- Bilateral and symmetrical involvement of large and small joints is typical of rheumatoid arthritis
- Lower limb asymmetrical oligoiarthritis and axial involvement would be typical of reactive arthritis
- Exclusive inflammation of the first metarsophalangeal joints is highly suggestive of gout
156
What joints are commonly involved and spared in rheumatoid arthritis?
```
Involved= PIP, MCP, wrist, elbow, should, cervical spine, hip, knee, ankle, tarsal, MTP
Spared= DIP, thoracic spine, lumbar spine
```
157
What joints are commonly involved and spared in osteoarthritis?
```
Involved= 1st CMC, DIP, PIP, cervical spine, thoracolumbar spine, hip, knee, 1st MTP, toe IP
Spared= MCP, wrist, elbow, shoulder, ankle, tarsal joints
```
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What joints are commonly involved and spared in polyarticular gout?
```
Involved= 1st MTP, ankle, knee
Spared= Axial
```
159
What is synovial fluid?
Viscous fluid present in joint space of synovial joints (diarthroses)
- Synthesised by synovial lining cells
- Abnormal increase in synovial fluid volume is termed 'synovial effusion'
160
What causes non-inflammatory synovial effusions?
- Osteoarthritis
| - Mechanical defects
161
What causes inflammatory synovial effusions?
- Gout
| - Rheumatoid arthritis
162
When is it useful or important to examine synovial fluid?
- Mandatory when joint infection is suspected
| - Useful to confirm diagnosis in suspected crystal arthritis
163
What are characteristics of connective tissue disorders?
- Arthalgia and arthritis is typically non-erosive
- Serum autoantibodies are characteristics
- Rayndaud's phenomenon is common in these conditions
164
What are the clinical manifestations of SLE?
- Malar rash (erythema that spared the nasolabial fold)
- Photosensitive rash
- Mouth ulcers
- Hair loss
- Raynaud's phenomenon
- Athralgia and sometimes arthritis
- Serositis
- Renal disease- glomerulonephritis
- Cerebral disease - 'cerebral lupus'
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What is Sjogren's syndrome?
- Autoimmune exocrinopathy
- Typically diagnosed in middle ages females
- Exocrine gland pathology results in dry eyes, dry mouth and parotid gland enlargement
- Commonest extra-glandular manifestations are non-erosive arthritis and Raynaud's phenomenon
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What is inflammatory muscle disease?
- Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) rash
- Skin changes in dematomyositis: helitrope, Gottron's papules, subcutaneous calcinosis, mechanic's hands
- Associated with autoantibodies
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What is systemic sclerosis?
- Thickened skin with Raynaud's phenomenon: dermal fibrosis, cutaneous calcinosis, telangiectasia
- Skin changes may be limited or diffuse
168
What is overlap syndrome?
- When features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease we can use the term overlap syndrome
169
What substance makes synovial fluid viscous?
Hyaluronic acid
| - A non-sulphated glycosaminoglycan
170
What is a key pathological finding in osteoarthritis?
Irreversible loss of articular cartilage
171
What is a proteoglycan?
Glycoproteins containing sulphated glycosaminoglycan chains
| e.g. Aggrecan
172
What is a glycosaminoglycan?
Repeating polymers of disaccharides
e. g.
- Chondroitin sulphate
- Keratan sulphate
- Hyaluronic acid
