Week 2 Flashcards
1
Q
what is inflammatory muscle disease
A
- Idiopathic Inflammatory Myopathies (IIM) are a heterogeneous group of inflammatory myopathies characterised by immune-mediated muscle injury
2
Q
Epidemiology of inflammatory muscle disease
A
- Severely different types, it is relatively rare
- IIM is the most common group of inflammatory myopathies, and includes dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM)
3
Q
Aetiology and Pathogen of Inflammatory muscle disease
A
– the exact cause is unknown, but it is believed to be an autoimmune-mediated process
4
Q
clinical features and diagnosis of inflammatory muscle disease
A
DM: Characterised by skin manifestations (e.g., heliotrope rash, Gottron’s papules) and muscle weakness. It seen more commonly in females, with peak prevalence occurring in children at about 7 years of age, and in adults between 30 and 50 years of age
PM: Defined by proximal muscle weakness and elevated muscle enzymes but lacks specific autoantibodies. It is predominantly seen in females, and commonly diagnosed at about 20 years of age
IBM: Presents with both proximal and distal muscle weakness, often with rimmed vacuoles on muscle biopsy. Inclusion body myositis is more common in men over 50 years of age with a slow onset
5
Q
what is infectious myositis
A
infection in the muscle
6
Q
aetiology and pathogen of myositis
A
caused by bacterial, viral, parasitic or fungal infections
occur through haematogeneous spread or direct muscle invasion
7
Q
what is Fibromyalgia Syndrome (FNS)
A
- Most common cause of chronic widespread musculoskeletal pain, often accompained by fatigue, cognitive disturbance (memory problems), psychiatric symptoms and multiple somatic symptoms
8
Q
Aetiology of Fibromyalgia Syndrome
A
- Unknown
- FMS is thought be the result of genetic (inherited) and environmental factors (such as exposure to a virus or illness)
- Fibromyalgia is more common in people with lupus or rheumatoid arthritis, an illness such as a virus (or a recent illness or infection), irritable bowel syndrome (IBS), tension headache, and migraine, pain from an injury or trauma, emotional stress and depression, family history of fibromyalgia, obstructive sleep apnea, restless legs syndrome, previous pain syndromes and mood disorders
9
Q
Pathophysiology of Fibromyalgia
A
- uncertain
- develop as a result of maladaptive biological response to physical/psycho stresses in genetically predisposed people
- pain processing problems
- ## elevated excitatory neurotransmitters and decrease in serotinoin and norepionphrine in spinal cord at level of descending pathways
10
Q
classification of Fibromyalgia
A
- chronic widespread pain
- diffuse pain in at least 4 of 5 body regions and is associated with signifcant emotional distress or functional disability
11
Q
Epidemiology of Fibromyalgia
A
est 1 mill experience chronic pain condtion.
12
Q
clinical manifestations of Fibromyalgia
A
- anxiety, depression, PTSD
- Cognition imapirment
- Insomnia
- neurpathic pain
- headache, stomach ache,
- chemical sensitivity
- morning stiffness not exceeding 60 mins
13
Q
Myasthenia Gravis (MG)
what is it
A
autoimmune disorder affecting neuromusclar junction
fluctuating motor weakness
14
Q
Aetiology of Myasthenia Gravis
A
genetically susceptible individuals
Infection, immunisation, surgery can be precipitating factors
15
Q
Myasthenia Gravis Epidemiology
A
any age
24.9% per 1 mil
higher in women age 16-64
higher in men 65+
16
Q
Myasthenia Gravis Pathophysiology
A
- neuromusclar junction
- weakness due to pathogenic autoantibodies against against the functionally important proteins in the post-synaptic membrane
- predominately the Ach receptors
17
Q
Myasthenia Gravis clinical manifestations
A
cannot be cured
detectable autoantibodies, muscle weakness fluctuates but worsens w time
occurs in eyes, bulbar, trunk, extermities
more in prox limbs then dist (arms more then legs)
exertion-induced muscle weakness
18
Q
what is Osteogenesis Imperfecta
A
rare, hereditary connective tissue disease characterised by extreme fragility leading to fractures and other complications (BRITTLE BONE)
19
Q
what is Osteochondrosis
A
- group of conditions related to interrupted blood supply to bone, affecting children
(Scheuermann, Legg-Clave-Perthes, Osgood-Schlatter) - disease of joint in children
- interruption of blood supply to bone, particular epiphysis
20
Q
what is Scoliosis
A
lateral deviation of spinal column that can idiopathic, congenital or neuromuscular
21
Q
Osteogenesis Imperfecta manifestations and info
A
- characterised by defective synthesis of type 1 collagen
- fragility, thin poorly developed bones, defective connective tissue
22
Q
Osteogenesis imperfecta treatment
A
- Bisphosphonates can increase cortical bone width and increase bone strength (MEDS)
- physio to increase strength of muscles
- (hydro therapy, change positions)
23
Q
General info on Scheuermann’s Disease
A
Spinal
- vertebrae grow unevenly with respect to sagittal plane
- wedging shape of vertebrae causing kyphosis
- apex of curve, located in thoracic
- back pain, hunchback, roundback, lordosis in lumbar, tight hamstrings
24
Q
What is Legg-Calve-Perthes Disease
A
- Syndrome of idiopathic avascular necrosis of the femoral epiphysis, possibly due to repeated multiple vascular occlusive episodes that involve the femoral head
25
general info on Osgood Schlatters
- Non Artiuclar
- microfractures in patella tendon area insets into tib tub
- pain in front of knee, inflam and thickening of patella tendon, swelling, tenderness, increase prominance of tib tub
treatment = limit activity, tibial bands, cold, anti-inflam,
26
Scoliosis types
congenital (from birth), neuromuscular, adult de novo, adolescent idiopathic (unknown)
27
Scoliosis Aetiology
- idiopathic, congenital, neuromuscular, intraspinal, compensation for leg length
CHILDREN
- unclear (idiopathic)
- genetic contribution
- congenital = failure of segmentation or vert
- neuromuscular = cerebral palsy, polio
- or collagen/metabolic disorders
ADULTS
- de novo = degenerative changes with no previous history
- progression of adolescent idiopathic/congenital or early onset
- can be secondary to other conditions such as parkinsons
28
Scoliosis Epidemiology
- common paediatric
- 2-10 yr olds rare
- adolescent idiopathic is more common in females
29
Scoliosis Pathophysiology
CHILDREN/ADOLESCENTS
- vertebral bodies grow faster than the posterior elements, resulting primarily in lordosis
- lack of posterior growth affects vertebral bodies from increasing in height, forcing them to be distorted, leaving them to rotate to make space causing rotational lordosis
ADULTS
- degenerative = asymmetric degeneration of intervertebral discs and joints, leading to unbalanced loading
- asymmetric disc angulation can cause asymmetric loading, which throughout adult leads to ongoing curve
30
congenital scoliosis
- Failure of formation
Absence of a portion of the vertebra – hemivertebra and wedge vertebra
- Failure of segmentation
Absence of normal separation between vertebrae
31
neuromuscular scoliosis
- Neuropathic or myopathic diseases
Cerebral palsy, myelodysplasia
Duchenne muscular dystrophy
32
idiopathic scoliosis
- 3 groups (structural curve, no cause)
Infantile – birth – 3 yrs
Juvenile – 4/10 yrs
Adolescent – 11+ yrs
33
manifestations of scoliosis
- High shoulder, prominent hip or projecting scapula
- Usually painless although pain may be associated with severe cases
- Shortness of breath and GIT disturbance
- back pain, postural imbalance and/or neurologic deficits e.g., weakness, numbness
- Congenital and AIS have onsets during the growing years and may progress and become symptomatic during adulthood
- Untreated, progressive AIS is associated with restrictive lung disease, pain, and severe deformity later in life
34
osteogenesis imperfecta aetiology
- Occurs secondary to mutations in the COL1A1 and COL1A2 genes
34
osteogenesis imperfecta Epidemiology
- Between 1 in 10,000 to 1 in 20,000 live births
35
osteogenesis imperfecta pathogenesis
- due to defects in genes involved in production, folding, stability, processing, and secretion of type 1 collagen, osteoblast function, or bone matrix mineralisation
-
36
Osteogenesis Imperfecta clinical manifestations
- Short stature, bone deformities, and recurrent fractures
- The goals of therapy for patients with OI are to reduce fracture rates, prevent long-bone deformities and scoliosis and minimise chronic pain
37
Legg-Calve-Perthes Disease Epidemiology
- LCP usually occurs between the ages of 3 to 12
- Highest rate if occurrence at 5-7 years
- Affects 1 in 1200 children under the age of 15 and occurs most commonly in male patients with male to female ratio 4:1
38
Legg-Calve-Perthes Disease Aetiology
- unknown
has to do with distruption of blood supply to femoral epiphysis , such as repetitive trauma etc
39
LCP pathophysiology
- femoral head to collapse and regrow
1. Necrosis – disruption of the blood supply leads to infarction of the femoral capital epiphysis, particularly the subchondral cortical bone. Subsequently, this leads to a cessation of the growth of the ossific nucleus. The infarcted bone softens and dies.
2. Fragmentation: The body reabsorbs the infarcted bone.
3. Reossification: Osteoblastic activity takes over, and the femoral epiphysis re-establishes.
4. Remodelling: The new femoral head may be enlarged or flattened. It reshapes during growth. Those that respond to conservative treatment will usually show healing in 2 to 4 years
40
LCP clinical man and physio treatment
- trendelenburg gait
- MRI
- Restricted movement
- strengthen adbuctor and stabilisers of gait
41
Osteomalacia and rickets
deficit in calcium and phosphate
OM only occurs when the growth plate is fused
42
Osteomalacia Aetiology
- Osteomalacia involves impaired mineralisation of the bone matrix
- results from decreased or defective mineralisation of newly osteoids (newly formed bone matrix) at sites of bone turnover
- Development occurs through mechanisms that cause hypocalcaemia, hypophosphatemia or directly inhibit the mineralisation process
- Nutritional deficiency: Vitamin D and calcium deficiency are primary causes;
- Genetic disorders: X-linked hypophosphatemia: A rare hereditary disorder causing phosphate wasting and low calcitriol levels
- Tumour-Induced Osteomalacia: certain tumours secrete FGF23, leading to phosphate loss and bone weakening
- Drug-Induced Osteomalacia: Caused by prolonged use of medications like anticonvulsants, bisphosphonates,
43
Rickets aetiology
- Commonly caused by vitamin D deficiency due to severe maternal vitamin D deficiency during pregnancy
- Can occur despite adequate vitamin D levels if there is insufficient intake or absorption of calcium by the child
44
Epidemiology of osteomalacia
In adults
- vitamin D deficency
45
Rickets epidemiology
not common in aus
- 4.9% per 100,000 children under 15
- most in children with dark skin pigment partially girls
46
pathophysiology of osteomalacia
- hypocalcaemia, phosphate reabsoption decreases
- parathyroid glands secrete parathyroid hormone to release calcium from bone to increase calcium
- phosphorus excreted from kidneys
47
rickets pathophysiology
- Occurs when the mineralisation of growth plate cartilage is disrupted due to a deficiency of calcium or phosphorus
- prevents hypertrophic chondrocytes in the primary spongiosa of the growth plate from undergoing apoptosis—an essential process for normal bone development
- - As a result, cartilage accumulates, causing the growth plate to expand and become structurally disorganised
- In addition to the widening of the growth plate, excessive unmineralized osteoid tissue builds up in the metaphysis (the region below the growth plate), leading to abnormal bone growth and deformation
- These changes alter the overall shape of the affected bones, increasing the diameter of both the growth plate and metaphysis
- If the deficiency is not corrected, the weakened bones can develop characteristic structural deformities
- The diagnostic gold standard for rickets is imaging, where plain radiographs or CT scans reveal widened and eroded growth plates, reflecting the disruption in normal bone formation
48
clinical manofestations of Rickets and OM
- bone pain, altered mobility, muscle weakness, pathological fractures, dorsal kyphosis,
49
osteopenia what is it
decrease in bone mineral density (BMD)
not low enough to meet oesteoporsis standard tho
50
Osteopenia aetiology
- genetic factors influence up to 80% of bone mineralisation
- non-modifiable (age related bone loss, genetics, sex, ethnicity)
- Modifiable (diet, physical inactivity, lifestyle, chronic illness)
51
Osteopenia epidemiology
- 4 fold higher for women then men
- males more likely to demonstrate secondary causes of decreased bone mass
52
Osteopenia Pathophysiology
- occurs secondary to uncoupling of osteoclast-osteoblast activity, resulting in a decrease in bone mass
53
Osteopenia Clinical Manifestation
- through scans and undetectable
- increased fracture risk
53
Osteoporosis what is it
- low bone mass, micro-architectural disruption and skeletal fragility resulting in decreased bone strength and increased risk of fracture
- aspects that impact BMD can be bone formation and reabsorption, bone geometry
54
Osteoporosis aetiology
- Age-associated osteoporosis (AAOP) results in reduced bone mass and increased fracture risk due to various intrinsic and extrinsic factors, such as mechanical unloading, hormonal imbalances, metabolic changes, cognitive decline, inflammation, and circadian rhythm disruptions
- Other causes of reduced BMD in both sexes include osteomalacia, malignancy (eg, multiple myeloma), Paget disease of bone, significant weight loss, reduced skeletal loading such as occurs with spinal cord injury, tobacco use and/or excessive alcohol intake, hyperthyroidism, and hyperparathyroidism
55
Osteoporosis Epidemiology
2022, 3.4% of people in AUS have osteoporosis
56
osteoporosis pathophysiology
- Osteoporosis is characterised by an imbalance in bone remodelling, where bone resorption exceeds bone formation, leading to a net loss in bone mass and deterioration of microarchitecture
osteoblast = build new bone
osteoclast = break down bone
- with age osteoclasts increase in activity whilst blasts decrease, leading to progressive decline in bone density
- oestrogen deficiency accelerates bone loss by increasing osteoclasts survival and decreasing osteoblasts
-
57
osteoporosis clinical manifestations
none until there is fractures
- vertebral fracture is most common
- height loss
- women get more hip fractures but it impacts men worse
58
Osteoarthritis what is it
Osteoarthritis (OA) is a complex, multifactorial disease that results from an imbalance between the breakdown and repair of joint tissues. Traditionally considered a "wear and tear" disease, it is now understood to have a strong inflammatory component, metabolic influences, and mechanical stress factors
59
Osteoarthritis aetiology
1. Ageing - cellular senescence, mitochondrial dysfunction and accumulation of advanced glycation end-products contribute to cartilage breakdown
2. Genetics - mutations in collagen types II, IX, and XI linked to early-onset OA
3. Obesity and Metabolic factors - being fat increases loading and contributes to systemic pro-inflammatory state through adipokines which exacerbate cartilage
4. inflammation and immune activation - Chronic low-grade inflammation, driven by cytokines, leads to increased production of matrix-degrading enzymes and synovial inflammation
5. Hormonal - Oestrogen deficiency in postmenopausal women has been implicated in OA development, particularly in the hands and knees
6. Anatomical - Joint shape, alignment, and congenital abnormalities
60
Osteoarthritis Epidemiology
most common joint disorder
- increases w age
- sex (women more likely)
- obesity
- occupational fcators
IN AUS
- higher in females then males age 25-34
- 49% of people over 75 have it
- high inner regional and low income
61
Osteoarthritis pathophysiology
1. Cartilage degradation
- The earliest changes occur in the articular cartilage, where the collagen network loosens, allowing proteoglycans to attract water and expand
- Chondrocytes become hypertrophic and overproduce matrix metalloproteinases and aggrecanases, leading to cartilage breakdown.
- Cartilage has limited repair capacity, so once collagen is lost, it is not replaced effectively
2. Bone changes
- Subchondral bone undergoes sclerosis (thickening), and osteophytes (bone spurs) form in response to mechanical stress
- Bone marrow lesions and cysts develop in advanced disease, contributing to pain
3. Synovial inflammation
- Synovitis, driven by proinflammatory cytokines (IL-1, IL-6, TNF-alpha), macrophages, and matrix fragments, leads to joint swelling and pain.
- Damage-associated molecular patterns activate the innate immune response, perpetuating inflammation
4. Soft tissue and neuromuscular involvement
- Ligaments, menisci, and joint capsules show degenerative changes
- Periarticular muscle weakness contributes to joint instability and altered biomechanics.
- Nerve sensitisation leads to chronic pain and altered proprioception
62
Osteoarthritis Clinical Manifestations
- pain increase w activity and improve w rest
- joint stiffness in morning for 30mins
- crepitus '
- reduced ROM
- joint deformities
- swlling
- disability
63
Rheumatoid Arthritis what is it
- RA is a chronic, systemic, autoimmune, inflammatory disorder
64
Rheumatoid Arthritis Aetiology
- unknown
- could be genetics and environmental, immune system
65
RA Epidemiology
approx 2% of AUS
66
RA Pathophysiology
- synovial inflammation and joint destruction
1. Initiation: Genetic and Environmental Factors
- Genetic Predisposition: Some people inherit genes that make them more likely to develop RA, especially a gene called HLA-DRB1 (part of the immune system). Other genes related to immune cell function also play a role as they affect immune regulation
- Environmental Triggers: Tobacco smoking is an established risk factor causing changes in proteins that the immune system mistakenly attacks (leading to autoantibody production).
2. Preclinical RA: Autoantibody Production and Immune Activation
- RA starts developing years before symptoms appear. The immune system begins making antibodies against the body's own proteins, such as:
Anti-citrullinated protein antibodies (ACPAs)
Rheumatoid factors (RFs)
- These antibodies attack modified proteins (citrullinated proteins), leading to inflammation. The increased levels of inflammatory chemicals (cytokines) circulate in the blood, preparing the body for disease
3. Synovial Inflammation: Transition to Clinical RA
- Once RA fully develops, the immune system attacks the lining of the joints (synovium), causing:
Swelling and pain due to inflammation
Thickened synovial membrane
Destruction of cartilage and bone over time
- Key players in joint inflammation
T cells – activate other immune cells at attack the joints
B cells – produce harmful antibodies (ACPA’s, RF)
Macrophages – release inflammatory substances (TNF, IL-6, IL-1) worsening joint damage
Fibroblast-like synoviocytes (FLS) – these behave like cancer cells, spreading inflammation and invading cartilage and bone
Osteoclasts – bone destroying cells activated in RA, leading to bone erosion
4. What causes the damage
- Cytokines (inflammatory messengers) worsen inflammation and joint destruction
67
RA clinical manifestations
gradual, symmetrical polyarthritis
- morning stiffness
- joint pain and swelling
- symmetrical arthritis
- decreased grip
- joint deformities
