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LCRS Year 2 > Musculoskeletal System > Flashcards

Musculoskeletal System Flashcards

1
Q

What are the five common metabolic bone disorders?

A
  • Primary hyperparathyroidism
  • Rickets / osteomalacia
  • Osteoporosis
  • Paget’s disease
  • Renal osteodystrophy
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2
Q

What are the symptoms of metabolic bone disease?

A 
Metabolic
- Hypo/hypercalcaemia
- Hypo/hyperphosphataemia
   • Low phosphate→renal damage
   • High phosphate→precipitation with calcium to form calcium phosphate causing widespread tissue damage

Bone

  • Pain
  • Deformity
  • Fractures
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3
Q

How is calcium stored in bone?

A

As inorganic hydroxyapatite

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4
Q

What makes a bone strong?

A

1) Mass
2) Material properties (matrix and mineral)
3) Microarchitecture
- Trabecular thickness
- Trabecular connectivity
- Cortical porosity
4) Macroarchitecture

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5
Q

What are the different ways of assessing bone structure and function?

A

1) Bone histology
2) Biochemical tests
3) Bone mineral densitometry (e.g. osteoporosis)
4) Radiology

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6
Q

What are the age related changes in bone mass?

A

Men always have higher bone mass than women.
Attainment of peak bone mass <30
Consolidation ∼30-40
Age related bone loss >40
Women have a faster loss of bone mass during the menopause

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7
Q

What biochemical investigations are performed in bone disease?

A

Serum:
- Bone profile
(calcium, corrected calcium [albumin], phosphate, alkaline phosphatase)
- Renal function
(creatinine, parathyroid hormone, 25-hydroxy vitamin D)
- Urine
(calcium/phosphate, NTX)

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8
Q

What are the biochemical changes in osteoporosis?

A 
Calcium: normal
Phosphate: normal
Alkaline Phosphatase: normal
Bone Form: ↑⟷
Bone Resorption: ↑↑
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9
Q

What are the biochemical changes in osteomalacia?

A

Calcium: normal or ↓
Phosphate: ↓
Alkaline Phosphatase: ↑

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10
Q

What are the biochemical changes in Paget’s disease?

A

Calcium: normal
Phosphate: normal
Alkaline Phosphatase: ↑↑↑
Bone Form: ↑↑

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11
Q

What are the biochemical changes in primary hyperparathyroid?

A

Calcium: ↑
Phosphate: ↓
Alkaline Phosphatase: normal or ↑
Bone Resorption: ↑↑

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12
Q

What are the biochemical changes in renal osteodystrophy?

A

Calcium: normal or ↓
Phosphate: ↑
Alkaline Phosphatase: ↑

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13
Q

What are the biochemical changes that occur in metastases (metabolic bone disease)?

A

Calcium: ↑
Phosphate: ↑
Alkaline Phosphatase: ↑
Bone Resorption: ↑

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14
Q

How is normal calcium homeostasis maintained?

A

1) Calcium is absorbed (mainly in the jejunum and ileum); either passive (not controlled; inefficient) or active (vitamin D controlled)
2) Exchange of Ca with bone
3) Kidneys filter blood and have compulsary loff of Ca per day

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15
Q

What is a normal total calcium in the serum?

A

2.15-2.56mmol/L

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16
Q

What is the total calcium in serum comprised of? What percentage are these of total calcium? What causes a shift in the percentages?

A

46% is protein bound
47% is free (ionized)
7% is complexed
Alkalosis causes a shift from free to protein bound calcium

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17
Q

What causes PTH to be released? What effect does the release of PTH have?

A

↓ plasma Ca²⁺ = ↑ PTH
Bone:
↑ resorption = release of Ca and phosphate
Kidney:
↑ phosphate excretion
↑ calcium reabsorption
↑ calcitriol formation → ↑ intestinal CaHPO₄ absorption

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18
Q

What is the rapid response system for low serum Ca?

A

PTH release

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19
Q

What also binds to the PTH receptor? Why is this clinically relevant?

A

PTHrP

A lot of this is produced during breastfeeding and by some tumours (which induces hypercalcaemia)

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20
Q

How is PTH release controlled?

A

The parathyroid gland monitors serum Ca through the calcium sensing receptor
Even at high calcium levels there is a base-line PTH secretion
There is a set-point (half of the maximal suppression of PTH)

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21
Q

What effect does PTH have on the kidney?

A

1) Internalises the Na/phosphate transporter from the membrane of the PCT to prevent reabsorption
2) Binds to receptor, activating Ca transport protein. Ca then binds to an intracellular protein which is transported through the cell and into the interstitial space by either a Ca²⁺ATPase or a Ca exchanger

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22
Q

How does PTH induce bone resorption?

A

PTH activates osteoblasts/stromal cells to express RANKL on their surface.
RANKL binds to RANK receptors on macrophages which stimulates osteoclasts to initiate bone resorption

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23
Q

What age and gender is primary hyperparathyroidism most common in?

A

50s

Female 3:1 Male

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24
Q

What are the causes of primary hyperparathyroidism?

A 
Parathyroid adenoma 80%
Parathyroid hyperplasia 20%
Parathyroid CA <1%
Familial syndromes
MEN1 2%
MEN2A rare
HPT-IT rare
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25
Q

How is primary hyperparathyroidism diagnosed?

A

Elevated total/ionized calcium with PTH levels elevated or in the upper half of the normal range

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26
Q

What are the clinical features of primary HPT?

A

Thirst, polyuria, tiredness, fatigue and muscle weakness
Stones, moans and psychic groans
Renal colic, dyspepsia, pancreatitis, constipation, nausea, anorexia, depression, drowsy, coma

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27
Q

At what point is a calcium level a medical emergency? Why?

A

> 3mmol/L
Kidney will shut down
Transporter will shut down so the patient will get rapidly dehydrated

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28
Q

What effect does acute and chronic PTH elevation have on bone resorption?

A

Acute (pulsatile): anabolic- builds bone

Chronic: catabolic- resorption

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29
Q

What are the actions of vitamin D?

A

Intestine:
- 1,25(OH)₂ vitamin D activates Ca and phosphate absorption in duodenum
Bone:
- Synergises with PTH, acting on osteoblasts to increase formation of osteoclasts through RANKL
- Increases osteoblast differentiation and bone formation
Kidney:
- Facilitates PTH action to increase Ca reabsorption in distal tubule

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30
Q

What is Rickets? What are the signs and symptoms?

A 
Inadequate vitamin D activity leads to defective mineralisation of the cartilaginous growth plate
Symptoms:
- Bone pain and tenderness
- Muscle weakness
- Lack of play
Signs
- Age dependent deformity
- Myopathy
- Hypotonia
- Short stature
- Tenderness on percussion
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31
Q

What are the causes of Rickets/osteomalacia?

A 
Vitamin D related:
- Dietary
- Gastrointestinal
  • Small bowel malabsorption / bypass
  • Pancreatic insufficiency
  • Liver/biliary disturbance
  • Drugs (phenytoin, phenobarbitone)
- Renal
  • Chronic renal failure
- Rare hereditary
  • Vitamin D dependent rickets
    → Type I - deficiency of 1α-hydroxylase
    → Type II- defective VDR for calcitriol
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32
Q

What hormone also causes phosphate loss in the PCT, as well as PTH? What metabolic bone disorder does this cause?

A

FGF-23

Osteomalacia/Rickets

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33
Q

What two hormones control phosphate homeostasis? What is the duration of action of these hormones?

A

PTH: Fast-acting hormone

FGF-23: Slow, long lasting hormone

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34
Q

What is osteoporosis?

A

Low bone density

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35
Q

What are the causes of osteoporosis?

A

1) High bone turnover
Increased bone resorption greater than increased bone formation
2) Low bone turnover
Decreased bone formation more pronounced than decreased bone resorption
3) Increased bone resorption and decreased bone formation

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36
Q

Deficiency in what hormone causes menopausal bone loss? What effect does it have?

A

Oestrogen
- Increases number of remodelling units
- Causes remodelling imbalance with increased bone resorption (90%) compared to bone formation (45%)
- Remodelling errors- deeper and more resorption pits lead to:
• Trabecular perforation
• Cortical excess excavation
- Decreased osteocyte sensing

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37
Q

Why would high urine calcium not be diagnostic of osteoporosis?

A

Because urine calcium will be high when a woman is post-menopausal

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38
Q

How is osteoporosis diagnosed? Explain this.

A

DEXA (Dual energy X-ray absorptiometry)
Measures 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

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39
Q

What is a FRAX? What does it measure and why?

A

Fracture Risk Assessment Tool
Uses hip bone
The commonest fractures in osteoporosis are vertebral fractures followed by hip fractures.

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40
Q

What propeptides can be measured in the blood and used to indicate bone formation?

A

P1NP = Procollagen type I N-terminal propeptide

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41
Q

What markers indicate bone resorption?

A

Serum CTX

Urine NTX

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42
Q

What is the process of collagen synthesis involved in bone formation?

A

1) 2 ‘Alpha 1’ and 1 ‘Alpha 2’ chain of type 1 collagen is produced by the osteoblast join
2) Extension peptides are cut off
3) 3 hydroxylysine molecules on adjacent tropocollagen fibrils condense to form a pyridinium ring linkage

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43
Q

Following treatment with anti-resorptive drugs, how long would it take to see results in an osteoporosis patient?

A

Bone resorption markers fall in 4-6 weeks
Expect a 50% drop of urine NTX by 3 months
Bone mineral density change in 18 months

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44
Q

What is alkaline phosphatase used to diagnose and monitor?

A

Pagets
Osteomalacia
Boney metastases

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45
Q

What is Chronic Kidney Disease Mineral Bone Disorder?

A

Skeletal remodelling disorders caused by CKD which contributes directly to vascular calcification
Contributes to excess mortality in CKD
CKD impairs skeletal anabolism, decreasing osteoblast function and bone formation rates

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46
Q

What in renal osteodystrophy? What is the progression of this disease?

A

Increased serum phosphate and reduction in calcitriol
SO
Secondary Hyperparathyroidism develops to compensate
BUT
Unsuccessful and hypocalcaemia develops
LATER
Parathyroids autonomous (tertiary)

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47
Q

What happens to the parathyroid gland in secondary hyperparathyroidism?

A

Parathyroid hyperplasia causing huge increase in parathyroid hormone

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48
Q

What are the functions of bone?

A

1) Mechanical
- support and site for muscle attachment
2) Protective
- vital organs and bone marrow
3) Metabolic
- reserve of calcium

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49
Q

What is the composition of bone, and their proportions?

A

Inorganic - 65%

Organic - 35%

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50
Q

What is contained within the inorganic portion of bone?

A
  • Calcium hydroxyapatite
  • 99% of Ca in the body
  • 85% of phosphorous
  • 65% of Na and Mg
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51
Q

What is contained within the organic portion of bone?

A
  • Bone cells

- Protein matrix

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52
Q

What are cortical bones?

A
  • Long bones
  • 80% of the skeleton
  • Appendicular
  • 80-90% calcified
    Mainly mechanical and protective
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53
Q

What are cancellous bones?

A
  • Vertebrae and pelvis
  • 20% of skeleton
  • Axial
  • 15-25% calcified
  • Mainly metabolic- Large surface
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54
Q

What are the two types of bone biopsy?

A

Closed
- needle - core biopsy usually taken from ASIC (Jamshidi needle)
Open
- For sclerotic or inaccessible lesions perfored under general anaesthetic (e.g. inner aspect of the pelvis)

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55
Q

What are the different types of bone cells?

A

1) Osteoblasts
2) Osteoclasts
3) Osteocytes

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56
Q

What are osteoblasts?

A

Build bone by laying down osteoid.

Mononucleated

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57
Q

What are osteoclasts?

A

Multinucleate cells of macrophage family.

Reabsorb bone or chew bone

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58
Q

What are osteocytes?

A

Osteoblast-like cells, which sit in lacunae in bone

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59
Q

What is RANK?

A

Receptor Activator for Nuclear Factor κβ

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60
Q

What inhibits osteoclastogenesis? How?

A

OPG = Osteoprotegerin

Inhibits RANK/RANKL binding by competing with RANK for RANKL

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61
Q

What turns on the RANK/RANKL system causing osteoclast differentiation?

A
  • PTH
  • Cytokines
  • Mechanical influences
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62
Q

Anatomically, what are the different types of bones? Give examples of each.

A 
Flat (Intramembranous ossification)
- Shoulder blades
Long (Endochondral ossification)
- Femur
Cuboid
- Vertebrae
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63
Q

What are the different classifications of bones? Explain the function of each.

A

1) Trabecular bone (cancellous)
The ends of long bones; porous, contains bone marrow
2) Compact bone (cortical)
Thick, dense, white bone; protective. Forms the hard exterior of bone
3) Woven bone (immature)
Abnormal, except in the base of teeth
4) Lamellar bone (mature)
Forms in response to gravity; thickens/makes bone strong

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64
Q

What is osteopaenia?

A

Reduced bone mass

Often results in fractures with little of no trauma

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65
Q

What are the three main categories of metabolic bone disease?

A

1) Related to endocrine abnormality (↓ Vit D; ↑ PTH)
2) Non-endocrine (e.g. age-related osteoporosis)
3) Disuse osteopaenia (lack of gravity)

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66
Q

What do you reach your peak bone mass?

A

30

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67
Q

What are the different types of osteoporosis?

A

Primary: age, post-menopause
Secondary: drugs, systemic disease (long-term steroids, some chemotherapy, anti-epileptics, thyroid treatment)

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68
Q

What is osteomalacia? What are the different types?

A

Defective bone mineralisation

1) Deficiency of vitamin D
2) Deficiency of PO₄ - usually chronic renal disease. Can’t make calcium hydroxyapatite

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69
Q

What are the different causes of low vitamin D?

A

1) Skin (e.g. culture- veils etc, winter)
2) G.I. disease (small bowel malabsorption)
3) Liver disease
4) Renal disease

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70
Q

What are the sequelae from osteomalacia?

A
  • Bone pain/tenderness
  • Fracture
  • Proximal weakness
  • Bone deformity
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71
Q

What type of labelling is performed to investigate osteomalacia?

A

Tetracycline labelling
Tetracycline is taken up into bones so bone sample can be taken from ASIC to determine the amount of bone growth in ∼21 days

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72
Q

What skeletal changes are seen in hyperparathyroidism?

A

Osteitis fibrosa cystica

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73
Q

What organs are affected in hyperparathyroidism?

A
  • Parathyroid gland
  • Bones
  • Kidneys
  • Proximal small intestine
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74
Q

What are the different types of hyperparathyroidism?

A

Primary:
- Parathyroid adenoma (85-90%)
- Chief cell hyperplasia within the parathyroid (rare)
Secondary:
- Chronic renal deficiency
- Vitamin D deficiency (due to feedback mechanism)

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75
Q

What would be shown on a hand X-ray of a patient with hyperparathyroidism? Why?

A

Lesions within the phalanges (Brown cell tumours)

Bone is broken down and replaced by fibrous tissue

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76
Q

What are the skeletal changes associated with chronic renal disease?

A

Can have one or a mixture:

1) Increased bone resorption (osteitis fibrosa cystica)
2) Osteomalacia
3) Osteosclerosis (thick bone)
4) Growth retardation
5) Osteoporosis

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77
Q

What are the features of renal osteodystrophy?

A

1) PO₄ retention (hyperphosphataemia)
2) Hypocalcaemia as a result of ↓ vitamin D
3) Secondary hyperparathyroidism
4) Metabolic acidosis
5) Aluminium deposition

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78
Q

What is Paget’s disease? What are the stages of this disease?

A

A disorder of bone turnover
Divided into 3 stages:
1) Osteolytic (bone is broken down rapidly)
2) Osteolytic-osteosclerotic (bone built again-mixed)
3) Quiescent osteosclerotic (cycle of break down→reformed)

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79
Q

Who is typically affected by Paget’s disease?

A

Onset >40y (3% Caucasians >55y)
♀=♂
Rare in Asians and Africans
Mono-ostotic 15% - remainder polyostotic

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80
Q

What are the main sites affected by Paget’s disease?

A

Spine 76%
Skull 65%
Pelvis 43%

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81
Q

What are the clinical symptoms of Paget’s disease?

A
  • Pain
  • Microfractures
  • Nerve compression (including spinal nerve and cord)
  • Skull changes may put medulla at risk
  • Deafness
  • ± haemodynamic changes, cardiac failure (↑ cardiac output to bone)
  • Hypercalcaemia
  • Development of sarcoma in area of involvement (1%- usually young people <30)
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82
Q

What is the haversian canal?

A

Space in mature bone where vessels run

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83
Q

What is Howship’s lacunae?

A

The bite mark left by osteocytes

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84
Q

What is Rheumatoid Arthritis?

A

Chronic joint inflammation that can result in joint damage

  • Site of inflammation is the synovium
  • Associated with atuoantibodies
    • Rheumatoid factor
    • Anti-cyclic citrullinated peptide (CCP) antibodies
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85
Q

What is Ankylosing Spondylitis?

A

Chronic spinal inflammation that can result in spinal fusion and deformity

  • Site of inflammation is the enthesis
  • No autoantibodies (‘seronegative’)
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86
Q

What are the different types of seronegative Spondyloarthropathies?

A
  • Ankylosing spondylitis
  • Reiters syndrome and reactive arthritis
  • Arthritis associated with psoriasis (psoriatic arthritis)
  • Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
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87
Q

What is Systemic Lupus Erythematosus?

A

Chronic tissue inflammation in the presence of antibodies directed against self antigens

  • Multi-site inflammation but particularly the joints, skin and kidney
  • Associated with autoantibodies:
    • Antinuclear antibodies
    • Anti-double stranded DNA antibodies
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88
Q

What are the different types of connective tissue diseases?

A
  • Systemic lupus erythamatosus
  • Inflammatory muscle disease: polymyositis, dermatomyositis
  • Systemic sclerosis
  • Siogren’s syndrome
  • A mixture of the above: ‘Overlap syndromes’
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89
Q

What HLA is associated with Rheumatoid arthritis?

A

HLA-DR4

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90
Q

What HLA is associated with Systemic Lupus Erythematosus?

A

HLA-DR3

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91
Q

What HLA is associated with Ankylosing Spondylitis?

A

HLA-B27

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92
Q

Where are MHC class I and class II cells found?

A

Class I: All cells

Class II: APCs

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93
Q

What antigen is presented by MHC class I? Give examples

A

Endogenous (intracellular)

  • Viral peptides
  • Tumour antigens
  • Self-peptides
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94
Q

What T cell recognises antigen presented by MHC class I? What is the response?

A

CD8 +ve T cell
(cytotoxic T cell)
Response: Cell killing

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95
Q

What antigen is presented by MHC class II? Give examples

A

Exogenous (extracellular)

  • Bacterial peptides
  • Self-peptides
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96
Q

What T cell recognises antigen presented by MHC class II? What is the response?

A

CD4 +ve T cell
(helper cell)
Response: Antibody response

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97
Q

What is the MHC peptide binding site made up of?

A

Walls: α-helical structures
Floor: β-pleated sheet

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98
Q

What is the pathological mechanism of Ankylosing Spondylitis?

A

Currently thought that the disease is due to abnormalities in both HLA-B27 and the interleukin-23 pathway.
HLA-B27 has a tendency to misfold and this causes cellular stress that trigger interleukin-23 release and triggers interleukin-17 production by
- Adaptive immune cells i.e. CD4 +ve Th17 cells
- Innate immune cells e.g. CD4 -ve CD8 -ve (‘double negative’) T cells

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99
Q

In what rheumatological conditions do you not see auto-antibodies?

A
  • Osteoarthritis
  • Reactive arthritis
  • Ankylosing spondylitis
  • Gout
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100
Q

What auto-antibodies are present in systemic vasculitis?

A

Antinuclear cytoplasmic antibodies

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101
Q

What auto-antibodies are present in rheumatoid arthritis?

A
  • Rheumatoid factor

- Anti-cyclic citrullinated peptide antibody

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102
Q

What auto-antibodies are present in systemic lupus erythematosus? What is the significance of each?

A
  • Antinuclear antibodies (ANA)
    All cases, non-specific
  • Anti-double stranded DNA antibodies (anti-dsDNA) (HIGH)
    Specific, serum level correlates with disease activity
  • Anti-cardiolipin antibodies (anti-phospholipid antibodies)
    Associated with risk of a/v thrombosis in SLE
  • Anti-Sm antibodies (ribonucleoprotein antigen)
    Specific for SLE

Patient will also have low complement levels

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103
Q

What auto-antibodies are present in diffuse systemic sclerosis?

A
  • Anti-Scl-70 antibody

also termed antibodies to topoisomerase-1

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104
Q

What auto-antibodies are present in limited systemic sclerosis?

A
  • Anti-centromere antibodies
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105
Q

What auto-antibodies are present in Dermato-/Polymyositis?

A
  • Anti-tRNA transferase antibodies

e. g. histidyl transferase (also termed anti-Jo-1 antibodies)

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106
Q

What auto-antibodies are present in Sjögren’s syndrome?

A

No unique antibodies but typically see:

  • Antinuclear antibodies -Anti-Ro and anti-La antibodies
  • Rheumatoid factor
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107
Q

What auto-antibodies are present in Mixed connective tissue disease?

A
  • Anti-U1-RNP antibodies
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108
Q

When would you see anti-Ro antibodies and anti-La antibodies in a patient?

A

Secondary Sjögren’s syndrome

Neonatal lupus syndrome (transient rash in neonate, permanent heart block)

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109
Q

When would you see anti-ribosomal P antibodies in a patient?

A

Cerebral lupus

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110
Q

If a patient has antinuclear antibodies when would further tests screen for?

A
  • Anti-Ro
  • Anti-La
  • Anti-centromere
  • Anti-Sm
  • Anti-RNP
  • Anti-ds-DNA antibodies
  • Anti-Scl-70

Cytoplasmic antibodies include:

  • Anti-tRNA synthetase antibodies
  • Anti-ribosomal P antibodies
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111
Q

What is the pathogenesis of systemic lupus erythematosus?

A

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

112
Q

What cytokines in rheumatology are released by T cells? What effect do they have?

A 
γ-IFN (Th1)
- Activates macrophages
IL-2 (Th1)
- Activates T and B cells
IL-6 (Th2)
- Activates B cells, acute phase response
113
Q

What cytokines in rheumatology are released by macrophages? What effect do they have?

A

IL-1
- Activates T cells, fever, pro-inflammatory
TNF-α
- Similar to IL-1: more destructive

114
Q

What is the dominant pro-inflammatory cytokine in the rheumatoid synovium?

A

TNF-α

115
Q

What are the actions of TNF-α released by an activated macrophage?

A
  • Proinflammatory cytokine release
  • Hepcidin induction
  • PGE₂ production
  • Osteoclast activation
  • Chondrocyte activation
  • Angiogenesis
  • Leukocyte accumulation
  • Endothelial cell activation
  • Chemokine release
116
Q

What treatments are available for rheumatoid arthritis in clinic?

A
  • Key treatment is anti-TNF-α
  • IL-6 and IL-1 blockade
  • Antibodies against B cell surface antigen CD20
117
Q

What is the role of RANKL in rheumatoid arthritis?

A

RANKL is produced by T cells and synovial fibroblasts in RA

  • Stimulates osteoclast formation (osteoclastogenesis)
  • Binds to ligand on osteoclast precursors (RANK)
  • Antagonised by decoy receptor- osteoprotegrin (OPG)
118
Q

What upregulates RANKL?

A
  • IL-1
  • TNF-α
  • IL-17
  • PTH-related peptide
119
Q

What monoclonal antibody acts against RANKL? What is this used to treat?

A

Denosumab

- Indicated for treatment of osteoporosis, bone metastases, multiple myeloma and Giant cell tumours

120
Q

What is the main treatment target of SLE? Give examples of drugs that use this target.

A

B cells

  • Rituximab → a chimeric anti-CD20 antibody used to deplete B cells
  • Belimumab → a monoclonal antibody against a B cell survival factor call BLYS
121
Q

What is Belimumab? How does it work?

A

Recombinant fully human IgG1 monoclonal antibody against BLYS
Inhibits activity of BAFF resulting in impaired B cell survival and reduced B cell numbers

122
Q

What do prostaglandins act on? What treatment inhibits them?

A

Lipid mediators of inflammation that act on platelets, endothelium, uterine tissues and mast cells

Glucocorticoids inhibit phospholipase A₂

  • Analgesia
  • Anti-pyretic
  • Anti-inflammatory
  • Anti-platelet
123
Q

What is rheumatoid arthritis?

A

Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints

124
Q

What are the key features of Rheumatoid arthritis?

A

Chronic arthritis
- Polyarthritis - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in and around joints
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Extra-articular disease can occur
- Rheumatoid nodules
- Others rare e.g. vasculitis, episcleritis
Rheumatoid factor may be detected in blood
- IgM autoantibody against IgG

125
Q

What joints are most commonly affected by rheumatoid arthritis?

A
  • Metacarpophalangeal joints
  • Proximal interphalangeal joints
  • Wrists
  • Knees
  • Ankles
  • Metatarsophalangeal joints
126
Q

What are sub-cutaneous nodules in rheumatoid arthritis?

A
  • Central area of fibrinoid necrosis surrounded by histocytes and peripheral layer of connective tissue
  • Occur in ≈30% of patients
  • Associated with:
    • Severe disease
    • Extra-articular manifestations
    • Rheumatoid factor
127
Q

What is rheumatoid factor? What is the significance of RF in rheumatoid arthritis?

A

Antibodies that recognise the Fc portion of IgG as their target antigen

  • Typically IgM antibodies (i.e. IgM anti-IgG antibody)
  • Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
128
Q

Why do citrullinated protein antigens develop in rheumatoid arthritis?

A

Peptidyl arginine deiminases (PADS) convert Arginine → Citrulline

  • PADs are present in high concentrations in neutrophils and monocytes and consequently there is increased citrullination of autologous peptides in the inflammed synovium
  • ACPA (Anti-cyclic citrullinated peptide antibody) is strongly associated with smoking and HLA ‘shared epitope’
  • Shared epitope preferentially binds citulline (non-polar) but not arginine (+ve charge) during inflammation- so ACPA more likely to develop among individuals with citrulinated autoantigens who have the shared epitope
129
Q

What are the extra-articular features of rheumatoid arthritis?

A

Common
- Fever, weight loss
- Subcutaneous nodules
Uncommon
- Vasculitis
- Ocular inflammation e.g. episcleritis
- Neuropathies
- Amyloidosis
- Lung disease - nodules, fibrosis, pleuritis
- Felty’s syndrome - triad of splenomegaly, leukopenia and rheumatoid arthritis

130
Q

What are the radiographic abnormalities in rheumatoid arthritis?

A 
Early
  - Juxta-articular osteopenia
Later
  - Joint erosions at margins of the joint
Later still
  - Joint deformity and destruction
131
Q

What are the pathological features of the synovium in rheumatoid arthritis?

A
  • Synovitis
  • Bone erosion
  • Pannus
  • Cartilage degradation (joint space narrowing)
132
Q

What is synovium? What type of collagen is it made of?

A

1-3 cell deep lining containing macrophhage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)

Type I collagen

133
Q

What is synovial fluid?

A

Hyaluronic acid-rich viscous fluid

134
Q

What is articular cartilage made of?

A

Type II collagen

Proteoglycan (aggrecan)

135
Q

What is the pathogenesis of rheumatoid arthritis?

A

Synovial membrane is abnormal in rheumatoid arthritis
The synovium becomes a proliferated mass of tissue (pannus) 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
- excess pro-inflammatory vs anti-inflammatory cytokines (‘cytokine imbalance’)

136
Q

What are the potential treatments for rheumatoid arthritis?

A
  • TNF-α inhibition: achieved through parenteral administration (most commonly subcutaneous injection) or antibodies or fusion proteins
  • IL-6 and IL-1 blockade available
  • B cell depletion by IV administration of antibody against B cell surface antigen, CD20
137
Q

How is joint damage prevented in rheumatoid arthritis?

A
  • Multidisciplinary approach e.g. physiotherapy, occupational therapy, hydrotherapy, surgery
  • Medication which includes:
    • Drugs that control the disease process (disease-modifying anti-rheumatic drugs: DMARDs)
    • Started early in the disease (joint destruction = inflammation x time)
  • Biological therapies offer potent and targeted treatment strategies
  • Important role of glucocorticoid therapy
    • preference to avoid long-term use (side effects)
    • useful as short-term treatment options in many settings e.g. to control flare of disease or control inflammation of single joint

DMARDs: steroid sparing agents (e.g. methotrexate)

138
Q

What are DMARDs? Give examples

A

Drugs that may induce remission and prevent joint damage
Achieve this by:
- reducing inflammation in the synovium
- slow or prevent structural joint damage e.g. bone erosions
Complex mechanisms of action and all have relatively slow onset of action (weeks)
E.g.
- Methotrexate - commonly used
- Sulphasalazine - commonly used
- Hydroxychloroquine - commonly used
- Leflunomide - uncommon
- Gold (rarely used now)
- Penicillamine (rarely used now)
All have significant adverse effects and therefore require regular blood test monitoring during therapy

139
Q

Give examples of chimeric antibody biological therapy used to treat rheumatoid arthritis?

A

(human/mouse)

  • Infliximab
  • Rituximab
140
Q

Give examples of full human antibody biological therapy used to treat rheumatoid arthritis?

A
  • Adalimuman

- Golimumab

141
Q

What is the main side effect of biological therapy treating rheumatoid arthritis?

A

Increased infection risk
- Can exacerbate TB
All treatments are expensive so in England their use follows NICE guidance

142
Q

What is reactive arthritis?

A

Sterile inflammation in the joints FOLLOWING infection especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter) infections

  • May be first manifestation of HIV or hepatitis C infection
  • Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
  • Symptoms follow 1-4 weeks after infection and this infection may be mild
  • Distinct from infection in joints (septic arthritis)
143
Q

What are the extra-articular manifestations of reactive arthritis?

A 
Ocular
- Sterile conjunctivitis
Genito-urinary
- Sterile urethritis
Skin
- Circinate balanitis
- Psoriasis-like rash on hands and feet 'keratoderma blennorrhagicum'
  • Enthesopathy
144
Q

What are the musculoskeletal symptoms of reactive arthritis?

A

Arthritis
- Asymmetrical
- Oligoarthritis (<5 joints)
- Lower limbs typically affected
Enthesitis
- Heel pain (Archilles tendonitis)
- Swollen fingers (Dactylitis)
- Painful feet (Metatarsalgia due to plantar fasciitis)
Spondylitis
- Sacroiliitis (inflammation of the sacro-iliac joints)
- Spondylitis (inflammation of the spine)

145
Q

What are the main differences between rheumatoid arthritis and reactive arthritis?

A 
Sex
  Rheumatoid: ♀>♂
  Reactive: ♂>♀
Age
  Rheumatoid: All ages
  Reactive: 20-40 years
Arthritis
  Rheumatoid: 
    - Symmetrical
    - Polyarticular
    - Small and large joints
  Reactive: 
    - Asymmetrical
    - Oligoarticular
    - Large joints
Enthesopathy
  Rheumatoid: NO
  Reactive: YES
Spondylitis
  Rheumatoid: NO (except atlanto-axial joint because synovial)
  Reactive: YES
Urethritis
  Rheumatoid: NO
  Reactive: YES
Skin Involvement
  Rheumatoid: Subcutaneous nodules
  Reactive: K. blennorhagicum; Circinate balanitis
Rheumatoid Factor
  Rheumatoid: YES
  Reactive: NO
HLA Association:
  Rheumatoid: HLA-DR4
  Reactive: HLA-B27
146
Q

How is Reactive Arthritis diagnosed?

A

Clinical diagnosis
Investigations to exclude other causes of arthritis e.g. septic arthritis:
- Microbiology
• Microbial cultures - blood, throat, urine, stool, urethral, cervical
• Serology (e.g. HIV, hepatitis C)
- Immunology
• Rheumatoid factor
• (HLA-B27)
- Synovial fluid examination
• Especially if only single joint affected

147
Q

How would you differentiate between septic arthritis and reactive arthritis?

A 
Synovial fluid culture
SA: Positive
RA: Sterile
Antibiotic therapy
SA: Yes 
RA: No
Joint Lavage
SA: Yes - for large joints 
RA: No
148
Q

How is reactive arthritis treated?

A

In majority of patients complete resolution occurs within 2-6 months. No role for antibiotics
Articular:
- NSAIDs
- Intra-articular corticosteroid therapy
Extra-articular:
- Typically self-limiting, hence symptomatic therapy
e.g. topical steroids and keratolytic agents in keratoderma
Refractory disease:
- Oral glucocorticoids
- Steroid-sparing agents e.g. sulphasalazine

149
Q

What is osteoarthritis?

A

Chronic, slowly progressive disorder due to failure of articular cartilage that typically affecting joints of the hand (especially those involved in pinch grip), spine and weight-bearing joints (hips and knees)

150
Q

What is typically affected by osteoarthritis?

A 
Joints of the hand
- Distal interphalangeal joints
- Proximal interphalangeal joints
- First carpometacarpal joint
Spine
Weight-bearing joints of lower limbs
- Especially knees and hips
- First metatarsophalangeal joint so common it's not reported as a problem
151
Q

What are Heberden’s nodes?

A

Osteophytes at the distal interphalangeal joints

152
Q

What are Bouchard’s nodes?

A

Osteophytes at the proximal interphalangeal joints

153
Q

What symptoms is osteoarthritis associated with?

A 
Joint pain
- Worse with activity, better with rest
Joint crepitus
- Creaking, cracking, grinding sound on moving affected joint
Joint instability
Joint enlargement
- e.g. Heberden's nodes
Joint stiffness after immobility ('gelling')
Limitation of motion
154
Q

What are the radiographic features of osteoarthritis?

A
  • Joint space narrowing
  • Subchondral bony sclerosis
  • Osteophytes
  • Subchondral cysts
155
Q

What are the differences between the radiographic changes in rheumatoid arthritis and osteoarthritis?

A 
Joint space narrowing
  RA: Yes
  OA: Yes
Subchondral sclerosis
  RA: No
  OA: Yes
Osteophytes
  RA: No
  OA: Yes
Osteopenia
  RA: Yes
  OA: No
Bony Erosions
  RA: Yes
  OA: No
156
Q

What are the features of a joint in osteoarthritis? Why does it develop?

A 
There is defective and irreversible articular cartilage and damage to underlying bone
- Worn away cartilage
- Cartilage fragments in fluid
Develops due to:
- Excessive loading on joints
AND/OR
- Abnormal joint components
157
Q

Describe the pathway in osteoarthritis

A 
Abnormal Abnormal
stress       cartilage
  ↓                   ↓
Normal     Normal
cartilage   cartilage
      Chondrocyte
        apoptosis
       ⤢             ⤡
Loss of       ⟷     Collagen
proteoglycans fibril damage
               ↓
      Cartilage fibrillation
      Osteophyte formation
      Subchondral bone sclerosis
158
Q

What are the properties of articular cartilage supporting it’s function?

A

Weight-bearing properties of articular cartilage depend on intact collagen scaffold and high aggrecan content
- Avascular and aneural structure
- Collagen >90% is type II
- Chondrocytes
- Proteoglycan monomers (aggrecan)
Central hyaluronic acid and non-covalently linked aggrecan
Negatively charged chemical groups of GAGs attract water

159
Q

What are proteoglycans? Give examples

A

Glycoproteins containing one or more sulphates glycosaminoglycan (GAG) chain
GAGs are repeating polymers of disaccharides and include:
- Chondroitin sulphate (glucuronic acid and N-aceyl galactosamine)
- Heparan sulphate
- Keratan sulphate (galactose and N-acetyl glucosamine)
- Dermatan sulphate
- Heparin
Proteoglycan examples:
Intracellular: Serglycin
Cell surface-associated: Betaglycan, Syndecan
Secreted into ECM: Aggrecan, Decorin, Fibromodulin, Lumican, Biglycan

160
Q

What is the major proteoglycan in articular cartilage?

A

Aggrecan

161
Q

What is the major component of synovial fluid? What are the disaccharides

A

Hyaluronic acid
The only-non-sulphated GAG
Maintains synovial fluid viscosity
Disaccharides are: Glucuronic acid and N-acetyl glucosamine

162
Q

What are the cartilage changes in osteoarthritis?

A
  • Reduces proteoglycan
  • Reduced collagen
  • Chondrocyte changes e.g. apoptosis
163
Q

What are the bone changes in osteoarthritis?

A

Changes in denuded sub-articular bone
- Proliferation of superficial osteoblasts result 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 joints margins (osteophytes)
- Heberden’s nodes (DIP joint)
- Bouchard’s nodes (PIP joint)

164
Q

What is the management procedure for osteoarthritis?

A
  • Education
  • Physical therapy: physiotherapy, hydrotherapy
  • Occupational therapy
  • Weight loss where appropriate
  • Exercise
  • Analgesia
    • Paracetamol
    • NSAIDs
    • Intra-articular corticosteroid injection
  • Joint replacement
165
Q

What autoimmune diseases affect connective tissue?

A
  • Rheumatoid arthritis
  • Sjögren’s syndrome
  • Systemic lupus erythematosus
  • Dermatomyositis
  • Polymyositis
  • Systemic sclerosis
166
Q

Who has increased risk of SLE? What is the prevalence?

A

M:F 1:9
Presentation 15-40 years
Increased in Afro-Caribbean, Asian and Chinese
Prevalence: 4-280/100,000

167
Q

What is affected by SLE?

A

Principally affects joints and skin

In severe cases affects lungs, kidneys and haematology

168
Q

What is the presentation of SLE?

A
  • Malaise
  • Fatigue
  • Fever
  • Weight loss
  • Lymphadenopathy
169
Q

What are the specific features of SLE? What other features are associated?

A
  • Butterfly rash
  • Alopecia
  • Arthralgia
  • Raynaud’s phenomenon

Other features:

  • Kidney inflammation
  • CNS inflammation
  • Heart inflammation
  • Lung inflammation
  • Accelerated atherosclerosis
  • Vasculitis
170
Q

What skin condition is associated with SLE? Why is this important?

A

Malar rash

Depth of rash is important. It can penetrate into the dermis. This is irreversible and must then be treated cosmetically

171
Q

What is the pathogenesis of SLE?

A 
Genetic predisposition
    ↓
Environmental triggers (apoptosis)
    ↓
Innate immune system activation (macrophages→APC)
    ↓
Adaptive immune system activation (APC→T cell→B cell→plasma cell=Ab)
   ↓
Immune complexes (Ab+tissue)
    ↓←Clinical disease onset
Aberrant amplification pathways
    ↓
Irreversible tissue damage
172
Q

What cellular alterations are seen in SLE?

A

Increased rate:
- Epigenetic deregulation of pro-apoptotic genes
↓ Release of nuclear material
Recognition of autoantigens
- Release of nuclear material with specific epigenetic patterns
- Epigenetic deregulation of genes involved in immune response

173
Q

What is the pathophysiology of autoantibody formation?

A

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…

174
Q

What are the laboratory tests for SLE? What is their significance?

A 
Antinuclear antibodies:
  ANA relatively non-specific, pattern important
  - Homogenous - Abs to DNA
  - Speckled - Abs to Ro, La, Sm, RNP
  - Nucleolar - topoisomerase - scleroderma
  - Centromere - limited cutaneous scleroderma
Anti-dsDNA and Sm
  - More specific but less sensitive
Anti-Ro and/or La
  - Common in subacute cutaneous LE
  - Neonatal lupus syndrome &amp; Sjögren's
Other tests
  - Increased complement consumption
  - Anti-cardiolipin antibodies
  - Lupus anticoagulant
  - β1 glycoprotein
Haematology
  - Lymphopaemia, normochromic anaemia
  - Leukopaenia, AIHA, thrombocytopaenia
Renal
  - Proteinuria, haematuria
  - Active urinary sediment
175
Q

How do you assess disease severity in SLE?

A
  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 - renal disease
    - Anti-cardiolipin antibodies
176
Q

What clinical features and laboratory markers are used to pre-empt severe attacks in SLE?

A 
Clinical Features:
- Weight loss
- Fatigue
- Malaise
- Hair loss
Laboratory Markers:
- ESR
- Increased complement consumption
- Increased anti-dsDNA
- Other Abs e.g. ANA and CRP poor indicators
177
Q

What is characteristic of mild SLE?

A

Joint ± skin involvement

178
Q

What is characteristic of moderate SLE?

A

Inflammation of other organs; pleuritis, pericarditis, mild nephritis

179
Q

What is characteristic of severe SLE?

A

Severe inflammation in vital organs:

  • Severe nephritis
  • CNS disease
  • Pulmonary disease
  • Cardiac involvement
  • AIHA, thrombocytopaenia, TTP
180
Q

What is the treatment for mild SLE?

A
  1. Paracetamol ± NSAIDs
    - Monitor renal function
  2. Hydroxychloroquine
    - Arthropathy
    - Cutaneous manifestations
    - Mild disease activity
  3. Topical corticosteroids
181
Q

What is the treatment for moderate SLE?

A 
Indication:
- Failure of hydroxychloroquine/NSAIDs
- Organ/life threatening disease
Corticosteroids:
- High initial dose to suppress disease activity
182
Q

What is the treatment for severe SLE?

A

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
183
Q

What novel treatments are available for treatment of severe SLE?

A

Mycophenolate Mofetil

  • Reversible inhibitor of inosine monophosphate dehydrogenase
  • Rate-limiting enzyme in de novo purine synthesis
  • Lymphocytes - dependent upon de novo purine synthesis

Rituximab

  • Anti-CD20 mAB therapy
  • Leads to depletion or B cells - Effective in lupus nephritis
184
Q

What is the prognosis in SLE?

A

15 year survival:

  • No nephritis 85%
  • Nephritis

Prognosis also worse if black male, low socio-economic status

185
Q

What is the bimodal mortality pattern of SLE?

A 
Early:
  - Renal failure
  - CNS disease
  - Infection
Late:
  - Myocardial infarction
186
Q

How do you assess gait in a GALS examination? What are you looking for?

A

Observe patient walking, turning and walking back
Look for:
- Smoothness and symmetry of leg, pelvis and arm movements
- Normal stride length
- Ability to turn quickly

187
Q

What does stiffness of joints in the morning indicate?

A

An inflammatory condition

188
Q

What does stiffness of joints after exercise indicate?

A

A mechanical joint problem

189
Q

How do you assess spine in a GALS examination?

A
  • Lateral cervical spine movement: try to place ear on the shoulder each side
  • Normal spine curves
    (cervical lordosis, thoracic kyphosis, lumbar lordosis)
  • Fibromyalgia: does mild pressure over either mid-point of each supraspinatus or gentle squeezing on skinfold over trapezius muscles elicit tenderness?
  • Lumbar and hip flexion: ask patient to bend forward and touch their toes with straight knees
190
Q

How do you assess arms in a GALS examination?

A
  • Pronation with elbows flexed
  • Supination with elbows flexed
  • Grip
  • Place tip of each finger on to the tip of the thumb to assess normal dexterity and precision grip
  • MCP squeeze test: squeeze across 2nd to 5th MCP joints. Discomfort suggests synovitis
  • Shoulder movement: Place both hands behind the head, then push elbows back
191
Q

How do you assess legs in a GALS examination?

A
  • Assess flexion of the hip and knee, whilst supporting the knee, passively internally rotate each hip, in flexion
  • Examine each knee for presence of fluid using ‘bulge’ sign and ‘patella tap’ sign
  • MTP squeeze test: squeeze across the MTP joints. Discomfort suggests synovitis
  • Inspect soles of the feet for rashes and/or callosites
192
Q

What is involved in a locomotor examination?

A 
- Inspection
Swelling, redness, deformity
- Palpation
Warmth, crepitus, tenderness
- Movement
Active, passive, against  resistance
- Function
Loss of function
193
Q

What is arthritis?

A

Refers to definite inflammation of a joint(s) i.e. swelling, tenderness and warmth of affected joints

194
Q

What is arthralgia?

A

Refers to pain within a joint(s) without demonstrable inflammation by physical examination

195
Q

What is dislocation?

A

Articulating surfaces are displaced and no longer in contact

196
Q

What is subluxation?

A

Partial dislocation

197
Q

What is a varus deformity?

A

Lower limb deformity whereby distal part is directed towards the midline e.g. varus knee with medial compartment osteoarthritis

198
Q

What is valgus deformity?

A

Lower limb deformity whereby distal part is directed away from the midline e.g. hallux valgus

199
Q

What is gout? What are the signs and symptoms?

A

Acute gout = arthritis
A disease in which tissue deposition of monosodium urate (MSU) crystals occurs as a result of hyperuricaemia and leads to one or more of the following:
- Gouty arthritis
- Tophi (aggregated deposits of MSU in tissue)
Gouty arthritis commonly affects the metatarsophalangeal joint of the bog toe
- Abrupt onset
- Extremely painful
- Joint red, warm, swollen and tender
- Resolves spontaneously over 3-10 days

200
Q

If you have swelling of articular soft tissue what tissue is involved and what is this indicative of?

A

Tissue: joint synovium or effusion
Indicates: Inflammatory joint disease

201
Q

If you have swelling of periarticular soft tissue what tissue is involved and what is this indicative of?

A

Tissue: subcutaneous tissue
Indicates: inflammatory joint disease

202
Q

If you have swelling of non-articular synovial what tissue is involved and what is this indicative of?

A

Tissue: bursa/tendon sheath
Indicates: inflammation of structure

203
Q

If you have swelling of bony areas what tissue is involved and what is this indicative of?

A

Tissue: articular ends of bone
Indicates: osteoarthritis

204
Q

What is enthesopathy? Give examples

A

Pathology at the enthesis i.e. the site where ligament or tendon inserts into bone
Examples include:
- Plantar fasciitis
- Achilles tendinitis

205
Q

What are the signs of irreversible joint damage from a locomotor examination?

A

Joint deformity
- Malalignment of two articulating bones
Crepitus
- Audible and palpable sensation resulting from movement of one roughened surface on another
- Classic features of osteoarthritis e.g. patello-femoral crepitus on flexing the knee
Loss of joint range or abnormal movement

206
Q

What is a swan-neck deformity?

A

Affect the ring finger- there is hyper-extension at the PIP joint and hyper-flexion at the DIP joint

207
Q

What is Boutonniére deformity?

A

Affects the little finger- there is hyper-flexion at the PIP joint

208
Q

What is Ankylosing Spondylitis?

A

A chronic condition which may cause joint deformity
A chronic inflammatory disease affecting:
- Sacroiliac joints (sacroiliitis) and deformity: may lead to spinal fusion (ankylosis) and deformity
- Entheses resulting in chronic enthesopathy
- Non-axial joints - hips and shoulders (common), others less frequently involved
- Strong association with HLA-B27
- Rheumatoid factor is negative

209
Q

What conditions are included in ‘sero-negative spondyloarthropathies’?

A
  • Ankylosing spondylitis
  • Reiter’s syndrome and reactive arthritis
  • Arthritis associated with psoriasis (psoriatic arthritis)
  • Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
210
Q

What are the signs of irreversible joint damage from a locomotor examination?

A

May be due to inflammation, degenerative arthritis or trauma and identified by:

  • painful restriction of motion in absence of features of inflammation
    e. g. knee ‘locking’ due to meniscal tear or bone fragment
  • instability
    e. g. side-to-side movement of tibia on femur due to ruptured collateral knee ligaments
211
Q

What are the different patterns of arthritis?

A

Determine by the number of joints involved:

  • Polyarthritis (>4 joints involved)
  • Oligoarthritis (2-4 joints involved)
  • Monoarthritis ( single joint affected)
212
Q

What joints are commonly affected in Rheumatoid arthritis?

A
  • PIP
  • MCP
  • Wrist
  • Elbow
  • Shoulder
  • Cervical spine
  • Hip
  • Knee
  • Ankle
  • Tarsal
  • MTP
213
Q

What joints are commonly affected in osteoarthritis?

A
  • 1st CMC
  • DIP
  • PIP
  • Cervical spine
  • Thoracolumbar spine
  • Hip
  • Knee
  • 1st MTP
  • Toe IP
214
Q

What joints are commonly affected by polyarticular gout?

A
  • 1st MTP
  • Ankle
  • Knee
215
Q

In what condition do you get subcutaneous nodules?

A

Rheumatoid arthritis

216
Q

In what condition do you get tophi?

A

Gout

217
Q

What is the term for an abnormal increase in synovial fluid volume?

A

Synovial effusion

218
Q

What is diathroses?

A

The term for a synovial joint (viscous fluid present in joint space)

219
Q

What are the different types of synovial lining cells?

A

Type A: macrophage-like

Type B: fibroblast-like

220
Q

What cells secrete hyaluronic acid?

A

Type B cells

221
Q

What is the composition of a synovial joint in synovitis?

A

Effusion is inflammatory exudate

- Inflammatory cells and mediators; reduced hyaluronic acid

222
Q

What is atherocentesis?

A

Synovial fluid examination using needle aspiration

223
Q

What crystal is seen in gout? Describe it.

A

Crystal: Urate
Shape: Needle
Birefringence: Negative

224
Q

What crystal is seen in pseudogout? Describe it.

A

Crystal: Calcium pyrophosphate dihydrate (‘CPPD’)
Shape: Brick-shaped
Birefringence: Positive

225
Q

What makes synovial fluid viscous?

A

Hyaluronic acid

226
Q

What is Sjögren’s syndrome? Who is commonly affected? What are the symptoms?

A 
Autoimmune exocrinopathy
- lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
Typically diagnosed in middle-age females (F:M = 9:1)
Exocrine gland pathology results in:
- Dry eyes (xerophthalmia)
- Dry mouth (xerostomia)
- Parotid gland enlargement
Extraglandular manifestations:
- Non-erosive arthritis
- Raynaud's phenomenon
Associated with autoantibodies:
- Anti-nuclear antibody - Anti-Ro and Anti-La antibodies
- Rheumatoid factor
227
Q

What is Inflammatory Muscle Disease? What are the associated symptoms?

A

Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
Associated with autoantibodies:
- Antinuclear antibody - Anti-tRNA synthetase antibodies (e.g. anti-Jo-1 = histidyl)
Elevated CPK, abnormal electromyography, abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells + B cells)
Associated with malignancy (10-15%) and pulmonary fibrosis

228
Q

What is systemic sclerosis?

A 
Thickened skin with Raynaud's phenomenon
- Dermal fibrosis, cutaneous calcinosis and telangiectasia
Skin changes may be limited or diffuse
- Diffuse systemic sclerosis
- Limited systemic sclerosis
229
Q

What are the skin changes associated with dermatomyositis?

A
  • Lilac coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
  • Red or purple flat or raised lesions on knuckles (Gottron’s papules)
  • Subcutaneous calcinosis
  • Mechanic’s hands (fissuring and cracking of skin over finger pads
230
Q

What is metabolic bone disease?

A

Systemic disorder of the skeleton resulting from s metabolic disturbance

231
Q

What are the different types of metabolic bone disease?

A
  • Osteoporosis
  • Osteomalacia and Rickets
  • Hyperparathyroidism: primary
  • Hyperparathyroidism: Secondary / Renal osteodystrophy
  • Paget’s disease
232
Q

What are the radiographic signs of metabolic bone disease?

A
  • Osteopenia

- Osteosclerosis

233
Q

What are the different scans used to detect metabolic bone disease? What do these scans show? What are the main scan that are used?

A
  • X-rays (density)*
  • CT scans (density/attenuation)
  • MRI scans (chemical/water content)
  • Radionuclide Bone Scans (Bone turnover NOT density
  • Bone Densitometry (density/attenuation)*
  • main scans used
234
Q

What is osteopenia? What conditions is it observed in?

A 
"Poverty" of bone
- a sign not a disease
Seen in:
- Osteoporosis
- Osteomalacia
235
Q

What is osteoporosis?

A

Decreased quantity of bone overall (bone mass), microstructure normal

  • Normal biochemistry
  • Fragility fractures / deformity / pain
  • Loss of cortical bone
  • Loss of trabeculae
  • Insufficiency fractures
236
Q

What is osteomalacia?

A
  • Vitamin D deficiency
  • Biochemistry: Vit D deficiency, Calcium normal/low, parathyroid hormone high, inadequate/delayed mineralisation
  • Radiology (age/growth plate closure)
  • Too little mineral: osteopenic and soft bone bends and deforms
  • Too much osteoid (Looser’s zones/pseudofracture)
  • If Ca stays low secondary hyperparathyroidism may be superimposed
  • ‘Codfish’ vertebra
237
Q

What areas of the body are at risk of Looser’s zones in osteomalacia?

A

Narrow lucency, perpendicular to bone cortex

  • pubic rami
  • proximal femer, scapula
  • lower ribs
238
Q

What are Codfish vertebrae?

A
  • Biconcave loss of height
  • Osteopenic
  • Pencilled-in margin
239
Q

What is the difference between osteomalacia and osteoporosis?

A 
Osteomalacia: less mineral
  - osteopenia
  - bend and bow before break
  - Codfish vertebrae: uniform spine deformity
Osteoporosis: less bone
  - osteopenia
  - break
  - anterior wedging
240
Q

What is the difference between osteomalacia and rickets?

A 
Osteomalacia: changes in mature bone
  - Osteopenia
  - Looser's zone's
  - Codfish vertebrae
  - Bending deformities
Rickets: before growth plate closure
  - changes related to growth plates dominate
  - changes of osteomalacia coexist
241
Q

What is Rickets?

A

Metaphysis most rapid growth = most obvious change

  • indistinct frayed matephyseal margin
  • widens growth plate (no calcifiction)
  • metaphysis indistict / frayed margin
  • cupping / splaying metaphyses - due to weight bearing
  • Rickety rosary
  • osteopenia
242
Q

What is Rickety Rosary?

A

Splayed and cupped anterior ends of ribs

243
Q

What are the PTH, Ca and phosphate changes in primary, secondary and tertiary hyperparathyroidism?

A

Primary HPT: ↑PTH ↑Ca ↓P
Secondary HPT: ↑PTH ↓Ca N/↓P
Tertiary HPT: ↑PTH ↑Ca ↓P

244
Q

What are the radiological changes in primary hyperparathyroidism?

A

Bone resorption

245
Q

What are the radiological changes in secondary hyperparathyroidism?

A

Renal osteodystophy

Resorption and increased density (anabolic and resorptive features of PTH)

246
Q

What bone resorption occurs in hyperparathyroidism? Describe each

A 
- Subperiosteal
  Radial aspect of middle and ring finger phalanges
- Subchondral (distal clavical, pubis
- Intracortical
- Brown tumours (osteoclastic activity

e.g. pepper-pot skull

247
Q

What causes slow bone loss?

A

Involutional osteoporosis

Bone has time to remodel/bone loss occurs according to mechanical needs

248
Q

What causes fast bone loss?

A

Hyperparathyroidism/disuse osteoporosis

Bone loss is too rapid. Loss does not cater to mechanical needs

249
Q

What radiological changes occur in renal osteodystrophy (chronic renal failure)?

A
  • Osteomalacia and osteoporosis
  • Secondary HPTH (sub-periosteal erosions, brown tumours, sclerosis-axial skeleton/vertebral end plates, rugger jersey spine, soft tissue calcification (arteries/cartilage)
  • Bone resorption
  • Bone sclerosis
250
Q

What are the mediators of bone metabolism?

A
  • Ca / P / vitamin D / Calcitonin
  • Other hormones: Tyroxine, growth hormone, glucocorticoids, oestrogens, androgens, insulin
  • Other factors: vitamin C and other nutrients, cytokines, prostaglandins, several growth factors
251
Q

What are the functions of collagen and mineral in bone?

A

Collagen provides the flexibility

Mineral provides the strength

252
Q

How often is skeletal tissue replaced?

A

Every 120 days

253
Q

What is the process of normal bone turnover?

A

Resorption- Ruffle border on osteoclasts releases enzymes to break down bone
Reversal- Osteoclasts apoptose and preosteoblasts form where bone must be formed
Formation- Osteoblasts build more osteoid tissue than osteoclasts broke down. Mineralisation of the bone
Resting

254
Q

What are bisphosphonates? What is the half life of bisphosphonates?

A

They destroy the cytoskeleton of osteoclasts, causing the ruffle border to break down so they can’t release enzymes and destroy bone
Half life is 10 years so even if the patient is taken off the drug it is still active in the body for 10 years

255
Q

What is the main side effect of bisphosphonates?

A

Drug actually causes fractures as bone ages and becomes more brittle
Microcracks form due to load on the bone, which are normally repaired. If they are not they build up and lead to a fracture
People taking bisphosphoates

256
Q

What is Denosumab? How does it work?

A

Monoclonal antibody
RANK-RANKL determines the osteoclast response that occurs
Denosumab is an antiresorpative, stronger than bisphosphonates which interferes with RANK-RANKL

257
Q

What is the mortality rate 30 days after a hip fracture?

A

10%

258
Q

What is Wolff’s Law?

A

Bone remodels according to the stress applied to it

Means that during child development you need to load the bones properly for them to develop correctly
If patients are not active the bone will start to resorb

259
Q

What is the process of fracture healing?

A

Week 1- Haematoma (or inflammation)
- Macrophages, leukocytes, IL-6, BMP etc
- Granulation tissue forms
- Progenitor cells invade
Weeks 2-3- Soft callus
- Chondroblasts and fibroblasts differentiate and form collagen (II) and fibrous tissue
- Proteoglycans produced → prevent mineralisation
- Chondrocytes release calcium into ECM and degrading enzymes to break down proteoglycans → allows mineralisation
Weeks 4-16- Hard callus
- soft callus invaded by blood vessels
- chondroclasts break down calcified callus
- replaced by osteoid (Type I collagen) from osteoblasts
- Osteoid calcifies → woven bone)
Weeks 17+- Remodelling
- Woven bone to lamella bone
- Shape relative to stress = Wolff’s law
- Medullary canal reforms

260
Q

What happens to the bone healing process in children?

A

It is much faster

Woven bone produced in 2 weeks

261
Q

What is a fracture?

A

A soft tissue injury with an underlying break in the bone

262
Q

What is a bone infection called?

A

Osteomyelitis

Difficult to get antibiotics to penetrate bone

263
Q

What are the different type of fracture?

A
  • Spiral fracture
  • Oblique fracture
  • Butterfly fragment
  • Transverse fracture
264
Q

What is a spiral fracture?

A

Fracture that goes diagonally across the bone, and occurs as a result of rotating the bone in the opposite direction to muscle force

265
Q

What causes an oblique fracture?

A

Normally a result of compressive forces

266
Q

What causes a butterfly fragment fracture?

A

Caused by a direct blow on the opposite side to the fragment

267
Q

What causes a transverse fracture?

A

Usually caused by a traction injury

268
Q

What is a Greenstick fracture? Who does it commonly occur in?

A

Occurs when the bone breaks but one side stays intact with the membrane. Much easier to treat as it is still quite stable
Occurs most commonly in children as their bones are more bendy

269
Q

What effect does exercise have on arthritis?

A

Sport makes you more likely to injure yourself and therefore more likely to get arthritis
Exercise is the most effective treatment for arthritis

270
Q

What did Hueter-Volkmann discover about growing bones?

A

Increased compression at the growth plate slows down longitudinal growth
Increased tension at the growth plate speeds up longitudinal growth

271
Q

What are the different types of varus alignment?

A

Neutral alignment: weight is passed straight through the middle of the knee joint so the load is spread evenly
Varus deformity: Weight is loaded onto the medial part of the knee joint resulting in a bowlegged appearance
Valgus deformity: Weight is loaded onto the lateral part of the knee joint resulting in a “knock-kneed” appearance

272
Q

Who is more likely to get varus deformity?

A

Football (and rugby) player

People who do a lot of sport

273
Q

Who is more likely to get a valgus deformity?

A

Tall thin women

274
Q

What effect does varus deformity have on arthritis?

A

More likely to develop arthritis

275
Q

What treatment is there for a varus deformity?

A

Osteotomy
X-ray to look at alignment and joint space
Straighten leg to get neutral alignment
Make a cut in the bone (so it remains attached laterally) and gently hinge it open then fix with a plate

Corrects alignment

276
Q

What causes developmental dysplasia of the hip? What is the treatment?

A

In utero the hip becomes malformed
- Steep slope on the acetabulum on one side compared to the other

Currently perform surgery after birth; if it is picked up really early the hips can be kept very abducted and the problem will resolve

277
Q

What are Cam and Pincer hips?

A

Cam impingement: (pistol grip deformity) extra bone forming a bump on the head of the femur
Pincer impingement: extra bone on the socket of the pelvis- hip socket is too deep

Both deformities prevent flexion of the thigh

LCRS Year 2 (6 decks)

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