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Year 2 LCRS 2 > Musculoskeletal > Flashcards

Musculoskeletal Flashcards

1
Q

What are the functions of bone?

A
  • Supporting the body’s shape (Mechanical)
  • Levers for muscle action
  • Protection of internal organs (Protective)
  • Site of blood cell formation
  • Mineral storage pool (Metabolic)
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2
Q

What are the two main properties of bone?

A
  • Cable-like flexibility (resistance to tension)

- Pillar-like stiffness (resistance to compression)

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3
Q

What makes bone resistant to tension?

A

The resistance to tension comes about because the osteoid is mostly a framework of collagen along with other bone proteins.

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4
Q

What makes bone resistant to compression?

A

Resistance to compression (stiffness) is a result of impregnation of collagen with a crystalline mineral called hydroxyapatite

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5
Q

What is hydroxyapatite?

A

a complex calcium hydroxyphosphate

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6
Q

What percentage of bone is organic and inorganic?

A

Bone is 65% inorganic and 35% organic.

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7
Q

What percentage of the body’s minerals are stored in bone?

A

99% of calcium
85% of phosphorus
65% of sodium and magnesium

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8
Q

What is osteoid?

A

The organic proportion of bone - composed of bone cells and matrix

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9
Q

How mineralised must bone be to be seen on an X-ray?

A

50%

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10
Q

What is the difference between woven and lamellar bone?

A
  • Immature bone is called woven bone and is characterised by haphazard organisation of collagen fibres, making it mechanically weak.
  • lamellar bone is mature bone which has a regular parallel alignment of collagen into lamellar sheets making it mechanically strong.
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11
Q

Where can woven bone be found?

A
  • Foetal bone
  • Woven bone is only found in adults at the site of repairing fractures
  • Paget’s disease
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12
Q

How can bones be classified anatomically?

A

Long, flat, sesamoid, irregular, short and stutural.

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13
Q

How can a long bone be divided anatomically?

A

epiphysis (ends) , metaphysics (before ends) and diaphysis (middle).

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14
Q

Lamellar bone has an outer and inner layer. What type of bone tissue makes these layers?

A
  • The outer layer is made of cortical/compact bone

- The inner layer is made of trabecular/spongey/cancellous bone

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15
Q

What percentage of skeletal mass is taken up by cortical/compact bone?

A

80%

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16
Q

How is cortical/compact bone organised?

A

Cortical bone is organised in osteons which are osteocytes arranged in concentric layers around a central canal, which contains one or more blood vessels.

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17
Q

What type of bone has mainly a metabolic function? And what type of bone has mainly a structural function?

A
  • Metabolic is trabecular/spongey/cancellous

- Structural is cortical/compact

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18
Q

What percentage of compact/cortical bone is calcified?

A

80-90%

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19
Q

How is trabecular/spongey/cancellous bone organised?

A

The matrix in spongey bone forms thin trabeculae branches, creating an open network. There are no capillaries in the matrix of the spongey bone.

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20
Q

How do nutrients reach the osteocytes in spongey bone?

A

Diffusion

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21
Q

What percentage of skeletal mass is taken up by trabecular bone?

A

20%

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22
Q

What percentage of cancellous bone is calcified?

A

10-15%

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23
Q

What is the name a main artery that supplies a bone?

A

A nutrient artery :)

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24
Q

Describe the features of the periosteum

A

Bone is covered by a periosteum which has a fibrous and cellular layer (outermost). The periosteum has key roles in bone growth and repair, is highly vascular and has a good sensory nerve supply (why we can feel our bones hurting)

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25
Q

What are the types of bone cells?

A
  • Osteoprogenitor cells
  • Osteocytes
  • Osteoblasts
  • Osteoclasts
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26
Q

What are the functions of an osteocyte?

A

The osteocytes have two major functions:

  • Maintaining the protein and mineral content of the surrounding matrix.
  • Participate in the repair of damaged bone, as they can convert to a less specialised type of cell, such as an osteoblast or an osteogenic cell.
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27
Q

What is the name of the process by which osteoblasts produce new bone matrix?

A

Osteogenesis

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28
Q

How are osteocytes formed?

A

Osteoprogenitor cells –> osteoblasts. Osteocytes are developed from osteoblasts that have become completely surrounded by bone matrix.

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29
Q

What is the function of an osteoblast?

A

Produce bone matrix. Before calcium salts are deposited, this organic matrix is called osteoid.

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30
Q

What is the function of an osteoprogenitor cell in an adult?

A

Osteoprogenitor cells are squamous stem cells that differentiate into osteoblasts. They are important in the repair of a fracture.

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31
Q

What is the function of an osteoclast?

A

Osteoclasts are cells that remove and recycle bone matrix

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32
Q

What is the name of the erosion process conducted by osteoclasts?

A

Osteolysis

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33
Q

What cells are osteoclasts derived from?

A

Osteoclasts are giant cells with 50 or more nuclei, and are descendent from macrophages.

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34
Q

What cells express RANK and RANKL

A
  • RANK (Receptor Activator for Nuclear Factor kB) is expressed on the cells of osteoclast precursor cells.
  • RANKL (RANK Ligand) is expressed on the multipotent stem cells of the osteoblast lineage, and also on B and T lymphocytes.
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35
Q

Describe the process of osteoclastogenesis

A

RANKL binding to RANK causes the differentiation to osteoclasts thus stimulating bone reabsorption.

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36
Q

How is osteoclastogenesis inhibited?

A

OPG (Osteoprotegerin) competes with RANK for RANK, thus inhibiting osteoclastogenesis. OPG is also expressed on multipotent stem cells and osteoblasts.

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37
Q

What cells express OPG

A

OPG is also expressed on multipotent stem cells and osteoblasts.

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38
Q

What are the types of ossification?

A
  • Intramembranous ossification occurs from existing vascular connective tissue
  • Endochondral ossification occurs within existing cartilage model
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39
Q

What percentage of the skeleton is undergoing remodelling?

A

5%

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40
Q

How is closed bone biopsy done?

A

A closed biopsy is done with a Jamshidi needle

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41
Q

Why would an open bone biopsy be done?

A

Alternatively, a bone biopsy can be open often for sclerotic or inaccessible legions.

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42
Q

Define metabolic bone disease

A

Metabolic Bone Disease is disordered bone turnover due to imbalance of various chemicals in the body leading to decrease in bone density and bone strength

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43
Q

How can bone strength be quantitatively measured?

A

Measuring cortical thickness, mineral density and size.

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44
Q

How can bone strength be qualitatively measured?

A

Looking at bone architecture, turnover, cortical porosity and trabecular connectivity.

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45
Q

What test/scans can assess bone structure and function?

A

Bone structure and function may be assessed in different ways: bone histology, biochemical tests, bone mineral densitometry, radiology.

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46
Q

What biochemical tests can be used to investigate metabolic bone diseases?

A 
SERUM:
•	Calcium
•	Corrected calcium
•	Albumin
•	Phosphate
•	PTH
•	25(OH)2D3

URINE
• NTX (molecules mobilised from bone by osteoclasts)
• Calcium
• Phosphate

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47
Q 
Describe the change(s) in:
- [calcium]
- [phosphate]
- [Alk Phosphate]
- Bone formation
- Bone reabsorption
seen in osteoporosis
A
  • Bone formation: normal/increased
  • Bone reabsorption: increased x2
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48
Q 
Describe the change(s) in:
- [calcium]
- [phosphate]
- [Alk Phosphate]
- Bone formation
- Bone reabsorption
seen in osteomalacia
A
  • Bone formation: n/a
  • Bone reabsorption: n/a
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49
Q 
Describe the change(s) in:
- [calcium]
- [phosphate]
- [Alk Phosphate]
- Bone formation
- Bone reabsorption
seen in Paget's disease
A
  • Bone formation: increase x3
  • Bone reabsorption: increase?
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50
Q 
Describe the change(s) in:
- [calcium]
- [phosphate]
- [Alk Phosphate]
- Bone formation
- Bone reabsorption
seen in Primary hyperparathyroidism
A
  • Bone formation
  • Bone reabsorption: increase x2
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51
Q 
Describe the change(s) in:
- [calcium]
- [phosphate]
- [Alk Phosphate]
- Bone formation
- Bone reabsorption
seen in PTH-like peptide secreting tumour
A
  • Bone formation
  • Bone reabsorption: increase
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52
Q

What should serum calcium concentration be?

A

2.15 - 2.56 mmol/l

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53
Q

What concentration of serum calcium is complexed, protein-bound, and free ionised?

A
  • protein-bound = 46%
  • ionised = 47%
  • complexed = 7%
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54
Q

How can osteoclast activity be measured?

A
  • Urine hydoxyproline (proline residues are hydroxylated in formation of collagen)
  • Urine and serum collagen cross-links
  • Tartate resistant acid phosphatases
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55
Q

What are the specific serum collagen crosslinks that can be measured in the urine? What is a problem in this method?

A

Urine collagen crosslinks such as pyridinium, N-terminal telopeptide (NTx) and C-Terminal telopeptide (CTx).

The results are not very reproducible, and there is a natural positive association with age. There is also diruninal variation in urine markers.

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56
Q

How can osteoblast function be measured?

A

Osteoblast function can be measured by Alkaline Phosphate, both total and bone-specific. Bone specific alkaline phosphatase is essential for mineralisation, as it regulates concentrations of phosphocompounds.

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57
Q

What are the primary causes of osteoporosis?

A

The primary causes of osteoporosis are age and being post-menopausal.

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58
Q

From what age does bone mass steadily decrease from?

A

Bone mass steadily decreases with age, in both men and women, after the age of 40

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59
Q

What bone changes does oestrogen deficiency cause?

A
  • Increases activation frequency of remodelling units
  • Causes remodelling imbalance as increases osteoblast apoptosis and decreases osteoclast apoptosis.
  • More remodelling errors means greater trabecular perforation and excess cortical excavation
  • Decreased osteocyte sensing
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60
Q

What biochemistry changes would you see in osteoporosis?

A

Serum biochemistry should all be normal. However, it is important to check for secondary endocrine causes.

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61
Q

What is the best predictor of fracture risk?

A

Bone Mineral Density

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62
Q

How is BMD measured?

A

Dual Energy X-Ray Absorptiometry (DXA) on vertebral bone as it is more metabolically active making it quick to respond to treatment. Hip measurements are also common as this is the second commonest place for fractures.

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63
Q

What situations would interfere with a BMD measurement?

A

Certain situations interfere with interpretation, for example degenerative change, osteoarthritis, vertebral fractures, metal artefacts, osteomalacia, vascular calcification, scoliosis, and Paget’s disease

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64
Q

Define osteoporosis in terms of the T-score

A

T-score is below -2.5, this is osteoporosis, between -1 and -2.5 is osteopenia.

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65
Q

What is the T-Score?

A

(measure BMD - young adult mean BMD)/(young adult standard deviation)

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66
Q

Who are the groups more at risk for osteoporosis?

A

People with:

  • oestrogen deficiency
  • corticosteroid treatment
  • maternal history of hip fractures
  • low BMI
  • other endocrine diseases
  • malabsorption
  • previous fragility fractures.
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67
Q

How can we expect urine cross-link markers to change with treatment of osteoporosis, page’s disease or primary hypoparathyroidism?

A

NTx to drop by 50%

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68
Q

Define osteomalacia

A

Osteomalacia is a condition of defective bone mineralisation. In children, Osteomalacia is called Rickets.

69
Q

What causes osteomalacia?

A

a deficiency in Vitamin D, or PO4(2-).

70
Q

What is the most common cause of hypocalaemia?

A

Vitamin D deficiency

71
Q

How does Vitamin D deficiency cause osteomalacia?

A

Vitamin D deficiency is the most common cause of hypocalcaemia. Hypocalcaemia causes an increased secretion of PTH. This leads to increased bone absorption and decreased formation. Although calcium concentrations are eventually re-normalised, the reduction of phosphate (kidney excretion because of PTH) means that bone cannot be re-mineralised effectively.

72
Q

What are the signs and symptoms of osteomalacia?

A

Symptoms:

  • axial bone tenderness and pain
  • increased fracture risk
  • proximal muscle weakness
  • bone deformities such as bowing

Signs:

  • age-dependent deformity
  • myopathy
  • hypotonia
  • short stature
  • tenderness on percussion
73
Q

What are the causes of vitamin D deficiency?

A
  • Lack of dietary intake
  • GI issues such as malabsorption, bypass, pancreatic insufficiency, liver/biliary disturbance, certain drugs
  • Chronic renal failure (renal osteodystrophy)
  • Resistance due to Vitamin D receptor mutation
  • Renal hypophophataemia
  • Oncogenic osteomalacia (mesenchymal tumours produce FGF-23 causing phophaturia and stopping 1-alpha-hyroxylase activity)
74
Q

What are the causes of primary hyperparathyroidism?

A

Primary hyperparathyroidism is caused by a parathyroid adenoma (80%), or chief cell hyperplasia (20%).

75
Q

What is usually the cause of secondary hyperparathyroidism?

A

to chronic renal deficiency, or vitamin D deficiency.

76
Q

What are the effects of PTH?

A
  • Increased serum calcium, by increased absorption from bone, kidney and gut.
  • Decreased serum phosphate, as renal excretion is greater than gut reabsorption.
  • Increased urine calcium as the increased renal absorption is overcome by the hugely increased filtered load due to increased serum calcium.
77
Q

What are the symptoms of hyperparathyroidism?

A

(due to hypercalcaemia):
• Stones: kidney stones
• Bones: Osteitis fibrosa cystica (increased bone absorption)
• Abdominal groans: acute pancreatitis, dyspepsia, constipation
• Psychic moans: psychosis, depression, impaired concentration.
• Polydipsia/Polyuria due to Ca/Na/K transporter
• Tiredness, Fatigue, Muscle Weakness

78
Q

Define renal osteodystrophy

A

Renal osteodystrophy is characterised by bone mineralisation deficiency, that is a direct result of the electrolyte and endocrine derangements that accompany chronic kidney disease.

79
Q

What are the sequelae of renal osteodystrophy?

A 
• Osteosclerosis
• Growth retardation
• Osteoporosis
• Hyperphosphataemia 
• Vitamin D deficiency: 
- Osteomalacia
• Hypocalcaemia (--> secondary hyperparathyroidism) Leading to:
- Osteitis fibrosa cystica
80
Q

What is the difference in the osteoporotic and osteomalacia bone?

A

Osteoporosis may be confused with osteomalacia, but in osteoporosis, the bones are porous and brittle, whereas in osteomalacia the bones are soft. This difference in bone consistency is related to the ratio of mineral to organic material. In osteoporosis, the mineral-to-collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic mineral content.

81
Q

Define Paget’s disease

A

Paget’s disease is a disorder of bone turnover whereby excessive breakdown and formation of bone is followed by disorganised bone remodelling

82
Q

What are the three stages of Paget’s Disease?

A
  1. Osteolytic: intense osteoclastic activity and bone resorption, with bone turnover as high as 20 times the normal rate.
  2. Osteolytic-osteosclerotic: osteoblasts begin to produce an abundance of woven bone, but mineralization is ineffective.
  3. Quiescent osteosclerotic: dense cortical and trabecular bone deposition dominates, but it is sclerotic, disorganized, and weaker than normal bone.
83
Q

What is the average age of onset of Paget’s disease?

A

40 years

84
Q

What percentage of caucasians have Paget’s disease?

A

3% of all Caucasians over 55 years of age.

85
Q

What percentage of Paget disease cases are mono-osmotic and poly-ostotic?

A

15% of cases are mono-ostotic (affecting one area), while the remainder are polyostotic.

86
Q

What virus has been linked with Pagetic bone?

A

Parvovirus

87
Q

What are the common sites of osteotic activity in Paget’s disease?

A

The primary sites affected include the skull (65%) and vertebral column (76%), followed by pelvis, femur, tibia, sternum and humerus.

88
Q

What are the symptoms of Paget’s disease?

A

. The clinical symptoms of Paget’s disease include pain, microfractures, nerve compression, skull changes, deafness, haemodynamic changes, hypercalcaemia, and development of a sarcoma in the effected area.

89
Q

What are the two main radiological signs of metabolic bone disease?

A

Osteopenia and Osteosclerosis

90
Q

What tools are used to identify osteopenia and osteosclerosis?

A
  • X-rays
  • Densitometry
  • MRI
  • CT
  • Radionucleotide bone scans
91
Q

What is osteopenia?

A

Osteopenia describes a state of bone poverty

92
Q

List the key radiological features of Osteoporosis

A
  • Osteopenia

- (decreased bone mass but normal microstructure)

93
Q

List the key radiological features of Osteomalacia

A
  • Osteopenia
  • (decreased bone mineralisation so soft bones)
  • Pseudofractures (Looser’s zones)
  • Codfish vertebrae (biconcave loss of height)
94
Q

List the key radiological features of Rickets

A
  • frayed metaphyseal margins
  • widened growth plates
  • bowing
  • rickety rosary
95
Q

List the key radiological features of hyperparathyroidism?

A
  • Subperiosteal, Subchondral, Intracortical bone reabsorption
  • brown tumours
96
Q

Describe the difference in bone loss from osteoporosis and from hyperparathyroidism?

A
  • Bone loss from osteoporosis is slow, bone has time to remodel
  • Bone loss is too fast from hyperparathyroidism to allow mechanical compensation
97
Q

What are the HLA polymorphisms that are associated with:

  • Rheumatoid Arthritis
  • SLE
  • Ankylosing Spondylitis
A

RA: HLA-DR4
SLE: HLA-DR3
Ankylosing Spondylitis: HLA-B27

98
Q

What is the difference is function between MHC Class 1 and MHC Class 2 molecules?

A
  • MHC Class 1 molecules are expressed in all cells. They present endogenous antigen such as viral peptides, tumour antigens and self-peptides. They present antigen to cytotoxic T cells, resulting in the cell’s death.
  • MHC Class 2 molecules are expressed in antigen present cells, which present exogenous antigen such as bacterial and self peptides to T-helper cells. This ultimately leads to antibody production.
99
Q

Name seronegative spondyloarthropathies

A
  • Ankylosing Spondylitis
  • Reiter’s syndrome
  • Reactive arthritis
  • Psoriatic artritis
  • Enteropathic synovitis
100
Q

What is the pathophysiology of Ankylosing Spondylitis?

A

In Ankylosing Spondylitis, we see cortical spinal inflammation that can result in spinal fusion and deformity. The site of inflammation is specifically the enthesis (the connective tissue between tendon or ligament and bone).

101
Q

Why does enthesopathy occur in Ankylosing Spondylitis?

A

It is associated with HLA-B27 and IL-23 and IL-17 release. This release is done by the adaptive immune cells (CD4 +) and double negative innate immune cells (CD4- CD8- T-Cells). The double negative T-cells only exist in the enthesis.

102
Q

Briefly outline the pathophysiology of Rheumatoid Arthritis

A

Rheumatoid Arthritis is a condition that results in the chronic inflammation of joints that can result in joint damage. Specifically, the site of inflammation is the synovium.

103
Q

What connective tissue diseases arrise from production of:

  • anti-Scl-70 Ab
  • anti-centromere Ab
  • anti-tRNA transferase Ab
  • anti-U1-RNP Ab
A

• Diffuse systemic sclerosis - Anti-Scl-70 antibody
• Limited systemic sclerosis - Anti-centromere antibodies
• Polymyositis - Anti-tRNA transferase antibodies
Mixed connective tissue disease - Anti-U1-RNP antibodies

104
Q

What is the main cell that secretes IFN-γ and what are it’s main effects?

A

Th1

Activates macrophages

105
Q

What is the main cell that secretes IL-1 and what are it’s main effect?

A

Macrophages

Activates T-cells, fever and pro-inflammary

106
Q

What is the main cell that secretes IL-2 and what are it’s main effect?

A

Th1

Activates T and B cells

107
Q

What is the main cell that secretes IL-6 and what are it’s main effect?

A

Th2

Activates B cells and acute phase response

108
Q

What is the main cell that secretes TNF-a and what are it’s main effect?

A

Secreted mainly by macrophages

Activates more macrophages, but has a more destructive and inflammatory role.

109
Q

What is the dominant pro-inflammatory cytokine in Rheumatoid Arthritis?

A

TNF-a

110
Q

How can Rheumatoid Arthritis with antibodies?

A
  • Against TNF-a
  • Against IL-1 and IL-6
  • Against CD20 to deplete B-cells
  • Against RANKL
111
Q

Why is there bone destruction in Rheumatoid Arthritis?

A

RANKL (stimulates osteoclast formation) is important in bone destruction in rheumatoid arthritis. It is produced by T-cells and Synovial fibroblasts in rheumatoid arthritis.

112
Q

What is anti-RANKL Ab called?

A

Denosumab

113
Q

How can SLE with antibodies?

A
  • anti CD20

- anti BLYS

114
Q

What is anti-CD20 Ab called?

A

Rituximab

115
Q

What is anti-BLYS Ab called?

A

Belimumab

116
Q

How are prostaglandins and leukotrienes made?

A

Phospholipase A2 generates arachidonic acid from diacylglycerol in cell membranes. Arachidonic acid enters two pathways:
• Cyclooxygenase pathway: arachidonic acid –> prostaglandins.
• Lipooxygenase pathway: arachidonic acid –> leukotrienes.

117
Q

What are the key features of Rheumatoid Arthritis?

A

• Chronic arthritis
- Polyarthritis where swelling of the small joints in the hand and wrist are common. Causes pain.
- Symmetrical sites of inflammation
- Early morning stiffness in and around joints
- May lead to joint damage and erosion
• Extra-articular disease can occur such as:
- Rheumatoid nodules
- Rarer ones such as vasculitis and episcleritis
• Rheumatoid factor (IgM antibody against the Fc part of IgG)

118
Q

Describe the epigenetic of Rheumatoid Arthritis

A

Roughly 1% of the population is affected. It is a significant cause of disability in young people. It has a 3:1 female:male incidence ratio.

119
Q

What DR chains are strongly associated with the shared RA epitope?

A

DR4 and DR1 have a shared epitope, which contributes to risk in producing anti-IgG antibodies

120
Q

What are the commonest affected joints in RA?

A
  • Metacarpophalyngeal joints
  • Proximal interphalangeal joints
  • wrists
  • knees
  • ankles
  • Metatarsophalangeal joints.
121
Q

What are Rheumatoid nodules?

A

This is where a central area of fibrinoid necrosis is surrounded by histiocytes and a peripheral layer of connective tissue.

122
Q

What are Rheumatoid nodules associated with?

A

Rheumatoid nodules are associated with severe disease, other extra-articular manifestations, and high levels of rheumatoid factor.

123
Q

What auto antibodies are associated with RA?

A
  • Rheumatoid Factor (Anti-IgG)

- Anti-Citrullinated proteins (ACPA = antibodies to citrullinated protein antigens)

124
Q

How does smoking increase the risk of RA?

A
  • Smoking enhances citrullination in lungs as it upregulates PAD ( Peptidyl Arginine Deaminases) which convert argentine to citrulline
  • The shared epitope preferentially binds to non-polar amino acids like citrulline rather than arginine.
  • ACPA (antibodies to citrullinated protein antigens) are generated because of this
125
Q

What are the common and rarer extra-articular features of Rheumatoid Arthritis?

A 
Common:
- Fever and weight loss
- Subcutaneous nodules (Rheumatoid nodules)
Rarer:
- Vasculitis
- Occular inflammation
- Neuropathies
- Amyloidosis
- Lung disease
- Felty's syndrome (splenomegaly, leukopenia and RA)
126
Q

What are the radiographic abnormalities present in Rheumatoid Arthritis?

A

In the early state of the disease, this would be seen as juxta-articular osteopenia. Later this would develop into joint erosions at margins of the joint before finally joint erosion and deformity.

127
Q

Describe the synovial changes in Rheumatoid Arthritis

A
  • The synovium has become a proliferated mass of tissue due to invasion of inflammatory cells, neovascularisation and lymphangiogeneisis.
  • The excess of pro-inflammatory cytokines such as TNFa contributes to this
128
Q

What is the role of TNFa in Rheumatoid Arthritis?

A
  • further pro-inflammatory cytokine release
  • leukocyte accumulation
  • angiogenesis
  • osteoclast activation
129
Q

What are the type of drugs used to treat Rheumatoid Arthritis?

A
  • DMARDs (Disease-modifying Anti-Rheumatic Drugs) which control the disease process, inducing remission
  • Biologic therapies (such as anti-TNF)
  • Glucocorticoid therapy to control flares
130
Q

Define Reactive Arthritis

A

Reactive arthritis is sterile inflammation in the joints following infection especially urogenital and gastrointestinal infections

131
Q

What genetic factor contributes to Reactive Arthritis risk?

A

HLA-B27 polymorphism

132
Q

What may Reactive Arthritis be an early manifestation of?

A

HIV or Hepatitis C infection

133
Q

List the musculoskeletal symptoms of reactive arthritis

A
  • Arthritis (Asymmetrical, oligoarthrtitis that especially affects lower limbs)
  • Enthesis presents as Achilles tendonitis, swollen fingers, painful feet
  • Spondylitis presents can present as sacroiliitis
134
Q

What are the non-musculoskeletal symptoms of reactive arthritis?

A
  • Skin inflammation (psoriasis like)
  • Eye inflammation (sterile conjunctivitis)
  • Genito-urinary inflammation (sterile urethritis)
135
Q

Compare the epidemiology of reactive arthritis to rheumatoid arthritis

A
  • reactive affects males more than females, compared to RA which affects females more.
  • RA affects all ages, while reactive arthritis tends to affect 20-40 year olds
136
Q

How is reactive arthritis diagnosed?

A
  • Microbiological investigations can be carried out to determine if there is infection to point to septic arthritis.
  • Serology can show the presence of HIV or Hepatitis C virus, which may be the cause of the reactive arthritis.
  • Immunological investigations can test for the presence of rheumatoid factor, or discover the HLA-B27 genotype.
  • Synovial fluid examinations may be conducted particularly when only one joint is affected.
137
Q

How is Reactive Arthritis treated?

A

In the majority of patients, their reactive arthritis completely resolves within 2-6 months. As it a sterile inflammation, there is no role for antibiotics. Articular symptoms are treated by NSAIDs or intra-articular corticosteroid therapy. Extra-articular symptoms are typically self-limiting and only require symptomatic treatment.

138
Q

Define osteoarthritis

A

Osteoarthritis is a chronic slowly progressive disorder due to failure of articular cartilage.

139
Q

What joints are typically associated with osteoarthritis?

A
  • hands (distal interphalangeal joint, proximal interphalangeal joints and first carpometacarpal joint)
  • spinal
  • weight-bearing joints such as knees and hips)
140
Q

What are the symptoms of osteoarthritis?

A
  • Joint pain
  • Joint crepitus
  • Joint instability
  • Joint enlargement
  • Joint stiffness
141
Q

What are the radiographic features of osteoarthritis?

A

joint space narrowing, subchondral bony sclerosis, osteophytes (nodes), and subcondral cysts.

142
Q

What radiographic features can be used to distinguish osteoarthritis from Rheumatoid arthritis

A

Subchondral cysts and osteophytes are not features of rheumatoid arthritis, so can be used as distinguishing features.

143
Q

What is the cause of osteoarthritis?

A

Osteoarthritis develops because of excessive loading on joints and/or due to abnormal joint components.

144
Q

What are the cartilaginous changes seen in osteoarthritis?

A
  • Reduced proteoglycans
  • Reduced collagen
  • Chondrocyte apoptosis
145
Q

What are the bone changes seen in osteoarthritis?

A

This leads to bone changes such as proliferation of osteoblasts resulting in sclerotic bone. Focal stress on the sclerotic bone can lead to focal necrosis. New bone formation at joint margins are called osteophytes.

146
Q

How is osteoarthritis managed?

A

Management of osteoarthritis is accomplished by education, physical therapy, occupational therapy, weight loss where appropriate, exercise, analgesia and finally joint replacement.

147
Q

What are the autoimmune connective diseases?

A
  • Rheumatoid Arthritis
  • Sjogren’s syndrome
  • SLE
  • Dermatomyositis
  • Polymyositis
  • Systemic sclerosis
148
Q

What is it called when an autoimmune connective disease transitions, and may cover parts of another connective disease?

A

Overlap syndrome

149
Q

Describe the epidemiology of SLE

A

Lupus is a chronic autoimmune disease affecting females more, to a ratio of 9:1. Being of afro-carribean, or Asian descent also increases your risk of developing lupus. It is a disease that usually presents at 15-40 years, but can even present in neonates.

150
Q

What organs does Lupus affect?

A

Principally the joints and skin, although also the lungs, kidneys and haematology.

151
Q

What is the severity of Lupus disease influenced by?

A

Genetic makeup of the disease

152
Q

What are the symptoms of lupus?

A

Early symptoms tend to be non-specific such as malaise, fatigue, fever and weight loss coupled with lymphadenopathy.
Specific features include:
- butterfly rash
- alopecia
- arthralgia
- Raynaud’s phenomenon
- Inflammation of the kidneys, CNS, heart and lungs

153
Q

What is the symptomatic criteria requirements for the diagnosis of SLE?

A

SLE is diagnosed using a range of criteria, with only 4 matched needed out of 11 symptoms for a positive diagnosis.

154
Q

Describe the malar rash in SLE

A

The butterfly rash can be very subtle, covering the cheeks and bridging the nose. The rash is made of blots (not pustules) due to localised inflammation, and so should not be itchy

155
Q

Apart from the butterfly rash, what skin changes can occur in SLE?

A

Depigmentation can occur when the inflammation reaches the dermis. Localised alopecia can occur for similar reasons.

156
Q

Describe the pathogenesis of SLE

A
  • Generic predisposition
  • Increased rate of apoptosis with a failure to clear nuclear material
  • Combined with B-cell hyperactivity leads to the generation of antinuclear antibodies (type III hypersensitivity)
  • Most damage is done by complement activation at sites of immune complex deposition
157
Q

How is SLE diagnosed?

A
  • 4 out of 11 diagnostic criteria
  • antinuclear antibody (ANA) test
  • pattern of fluorescent antibody test (homogenous)
  • Anti-dsDNA
  • Increased complement consumption
  • presence of anti-cardiolipin antibodies, lupus anticoagulant, and β1 glycoprotein also points towards SLE.
158
Q

How can antibodies be used to detect SLE?

A

The first thing to do is test for antinuclear antibodies (ANA) detected by immunoflourescent antibodies (indirectly). Although this is useful, it is not diagnostic. The pattern of fluorescence is important, as a homogenous pattern points towards antibodies to DNA (SLE), while a speckled pattern points to Ro, La, Sm, RNP telling a story of overlap syndrome.

Anti-dsDNA antibody test is extremely specific to SLE, but is less sensitive.

159
Q

How does a lupus patient’s haematology look?

A

A lupus patient’s haematology would show lymphopaenia, leukopeania, thrombocytopaenia, normocytic anaemia and AIHA (autoimmune haemolytic anaemia).

160
Q

What would a urine test from a lupus patient show?

A

Urine tests would show proteinuria, haematuria and an active urinary sediment.

161
Q

How is the severity of lupus assessed?

A
  1. Pattern of organ involvement
  2. Function of affected organs – using specific organ function tests such as protein:creatine ratio (kidneys), echocardiography, etc.
  3. Pattern of antibodies expressed - Anti-dsDNA, anti-Sm antibodies may indicate renal disease, and there may also be anti-cardiolipin antibodies to indicate CVS damage.
162
Q

How can a clinician pre-empt a severe lupus attack

A

A clinician can pre-empt a severe attack as there is usually warning that the disease is about to flair. Signs such as weight loss, alopecia, fatigue, malaise and a rash can prompt the doctor to do further tests to look at (mainly) complement consumption, but also ESR, increased anti-dsDNA and other anitbodies.

163
Q

How can SLE disease severity be divided?

A
  • Mild – joint and/or skin involvement
  • Moderate – inflammation of other organs presenting as nephritis, pleuritis, pericarditis etc.
  • Severe – severe inflammation in vital organs causing severe nephritis, CNS disease, pulmonary and cardiac involvement and haematological issues.
164
Q

How is mild SLE treated?

A

Mild disease is treated using NSAIDs or paracetamol for pain management. Hydroxycloroquine is usually quite effective in treating the skin, but topical steroids may need to be employed.

165
Q

How is moderate SLE treated?

A
  • To supress disease activity, IV methylprednisolone is given every 24 hours, with an initial oral dose for 4 weeks. This is reduced slowly over two or three months to 10mg daily, and then reduced slowly at 1mg per month.
  • Azathioprine
  • Mycophenolate mofetil
  • Rituximab
166
Q

How can Azathioprine be used to treat SLE?

A

Azathioprine is a very useful drug for treating moderate to severe disease (2.5mg/kg/day), and is an effective steroid sparing agent. It needs to be accompanied by regular FBC and biochemistry monitoring as it can cause bone marrow suppression.

167
Q

How can Rituximab be used to treat SLE?

A

Rituximab is used in anti-CD20 mAb therapy, and it leads to the depletion of B cells. It is effective in lupus nephritis.

168
Q

What is the prognosis a SLE?

A

Prognosis is usually a 15-year survival. With no nephritis, this is 85%, and with nephritis this is 60%. Prognosis is also worse if black, male, or of low socio-economic status.

Year 2 LCRS 2 (3 decks)

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