week 6 - ageing and degeneration

Question 1

functions of musculoskeletal system

Answer 1

enables an efficient means of limb movement
acts as an endoskeleton for protection and support
serves as a reserve for organic and inorganic molecules
provides an environment for marrow

Question 2

impact of ageing on body

Answer 2

affects the balance of mechanisms which ensure homeostasis within organs
alters tissue response to injury
associated with accumulation of genetic damage
elicits antagonistic or compensatory mechanisms - initially beneficial but chronicity leads to further damage resulting in phenotypic alterations
age related changes may overlap significantly with pathological syndromes

Question 3

generic processes with ageing

Answer 3

decreased amount of tissue
altered molecular disposition of the matrix
accumulation of degraded molecules
reduced efficiency of functional tissue elements
reduced synthetic capacity of differentiated cells
altered levels of trophic hormones, GFs and cytokines, or altered ability of cells to respond
alterations in the loading patterns of tissues or the tissues response to loading

Question 4

MSK ageing syndromes

Answer 4

osteoporosis - bones
osteoarthritis - joints
sarcopenia - muscle

Question 5

ageing within articular cartilage

Answer 5

very low rate of replication so vulnerable to ageing
50% of chondrocytes last between 40 and 80 years
ECM contains hydrophilic proteoglycans essential for maintaining internal swelling pressure
composition changes with age leading to reduction of water content with fragmentation of protein components and collagen leading to reduced tensile strength

Question 6

osteoarthritis pathogenesis

Answer 6

joint damage occurs (repeated loading and stress or injury) which triggers repair processes
these repair processes alter the structure of the joint over time causing features of:
localised loss of cartilage
remodelling of adjacent bone and foundation of osteophytes
mild synovitis

Question 7

bone ageing

Answer 7

reduction in number of osteoblasts and osteoblast proliferation
diminished ability of osteoblasts to sense and respond to mechanical forces
relative increase in numbers of osteoclasts
increase in bone turnover and a disruption of remodelling activity
gradual decline in secreted growth hormone with fall in levels of IGF-1

Question 8

hormonal changes in bone ageing

Answer 8

gradual decline in secreted growth hormone with fall in levels of IGF-1 along with decreased sensitivity to its effect (required for differentiation of osteoblasts)
oestrogen has an inhibitory effect on osteoclasts - increased bone resorption following menopause (decreased oestrogen levels after menopause)
increase in inflammatory cytokines from a lifetime exposure to antigens

Question 9

bone remodelling

Answer 9

activation - preosteoclasts are stimulated and differentiate under the influence of cytokines and GFs into mature active osteoclasts
resorption - osteoclasts digest mineral matrix
reversal - end of resorption
formation - osteoblasts synthesise new bone matrix
quiescence - osteoblasts become resting bone lining cells on the newly formed bone surface

Question 10

risk factors for osteoporosis

Answer 10

age, female, family, previous fracture, early menopause, long term glucocorticoid therapy, rheumatoid arthritis
alcohol, smoking, low BMI, poor nutrition, vitamin D deficiency, eating disorders, insufficient exercise, low dietary calcium intake

Question 11

diagnosis of osteoporosis

Answer 11

bone strength strongly related to its density
inverse relationship between BMD and fracture risk
to assess BMD use dual energy x-ray absorpsiometry (DXA) at hip and spine
reported in terms of t scores with t=0 as normal bone mass in young healthy women
t

Question 12

fragility fractures

Answer 12

from mechanical forces that would not normally result in fracture
force equivalent to a fall from standing height or less
most common in vertebrae, proximal femur and distal radius

Question 13

prevention of osteoporosis

Answer 13

maximise peak bone mass:
regular weight bearing exercise
healthy diet
sufficient vit D
avoid smoking
alcohol in moderation

Question 14

treatment of osteoporosis

Answer 14

antiresorptive - reduces bone turnover by inhibiting osteoclast activity:
bisphosphonates
denosumab
raloxifene
hormone replacement therapy
anabolic - stimulates bone formation:
teriparatide - stimulates osteoblast activity

Question 15

sarcopenia

Answer 15

progressive and generalised skeletal muscle disorder that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality

Question 16

severe sarcopenia

Answer 16

when all 3 criteria met:
low muscle strength
low muscle quality or quantity
low physical performance

Question 17

causes of primary and secondary sarcopenia

Answer 17

p - ageing
s - disease-related (advanced organ failure, malignancy, inflammatory or endocrine disease), activity-related (bed rest, deconditioning, sedentary lifestyle, zero gravity), nutrition-related (inadequate intake of energy and/or protein)

Question 18

diagnosis of sarcopenia

Answer 18

muscle function:
handgrip strength
chair stand strength
usual gait speed
timed up and go
muscle mass:
CT/MRI
DXA

Question 19

treatment of sarcopenia

Answer 19

no pharmacological therapies yet
resistance and aerobic exercise
attention to nutrition with increased protein intake - evidence less consistent
vitamin d supplementation in deficient patients

Question 20

consequences of MSK ageing

Answer 20

altered gait and balance leading to falls and fear of falls
increased risk of injury, particularly fracture
chronic pain
social isolation if living independently
loss of independence and admission to care home

Question 21

factors influencing birth rate

Answer 21

availability of contraception
women working
financial burden
abortion - availability and religious views
sexual health education
level of education
type of work - lower birth rates in urban areas

Question 22

factors affecting death rate

Answer 22

war
accessibility and quality of healthcare
droughts
famine
natural disasters
vaccinations
screening

Question 23

epidemiology

Answer 23

the science and practice which describes and explains disease patterns in populations

Question 24

difference between incidence and prevalence

Answer 24

i - number of new events occurring in a specific time period in a defined population - excluding prevalent cases
p - number of cases of disease or other health outcome present in a specific time period in a defined population

Question 25

functional ability

Answer 25

``` about having the capabilities that enable all people to be and do what they have reason to value includes a persons ability to: meet their basic needs learn, grow and make decisions be mobile build and maintain relationships contribute to society ```

Question 26

chronic musculoskeletal impact on quality of life

Answer 26

``` leading cause of chronic disease morbidity severe long-term pain long term activity limitation sleep disturbance exacerbate symptoms of anxiety and depression accessibility problems social interactions drug side effects ```

Question 27

affect of freefall conditions in space

Answer 27

zero gravity mimics some of the effects of ageing

Question 28

main cause of preventable falls in elderly

Answer 28

low muscle strength | falls are the main cause of accidental death in elderly

Question 29

describe the components of body mass in a young person

Answer 29

in a young adult: bone ~15% of body mass muscle ~30% in women and ~40% in men muscle and bone turnover is ~20% each year this falls with age - ~2% turnover in elderly

Question 30

factors impacting muscle and bone mass

Answer 30

complex interaction of mechanical demands, dietary, genetic and endocrine factors peak muscle and bone mass reached in early adult life progressive decline in muscle and bone mass after their early 30s muscle degeneration will be accompanied by bone degeneration

Question 31

function of inorganic and organic component of bone

Answer 31

i - hydroxyapatite crystals resist compression | o - collagen resists stretching

Question 32

role of PTH, vitamin D and calcitonin in bone remodelling

Answer 32

PTH - increases plasma Ca++ concentration by releasing it from bone vit d - increases Ca++ concentration and phosphate absorption from the gut and recovery from renal filtrate calcitonin lowers plasma Ca++ by reducing osteoclast activity

Question 33

what can disturb the balance of growth/breakdown of bone remodelling

Answer 33

endocrine factors eg menopause diet and lifestyle mechanical loading - exercise to promote

Question 34

physical consequences of prolonged space flight

Answer 34

fluid shifts, fluid and electrolyte loss - change in urine composition - drop in blood volume negative energy balance - not enough calories bone loss skeletal and cardiac muscle atrophy - leads to reduction in peak oxygen uptake radiation exposure

Question 35

impact of zero gravity on bone mass

Answer 35

spaceflight induces loss of bone due to increased bone resorption and decreased bone formation

Question 36

solutions for reduced bone mass after spaceflight

Answer 36

reduce resorption with alendronate - adsorbed onto hydroxyapatite crystals to slow the rate of bone turnover - slows growth and resorption maintain formation with heavy resistance exercise maintain nutrients - vitamin d supplementation other vitamins and minerals

Question 37

restricting body mass loss in space

Answer 37

limit extra vehicular activity exercise (bone and muscle) restrict energy expenditure increase food intake - difficult with lack of apetite increase calorie content - difficult with motion sickness

Question 38

effects of returnign to earth

Answer 38

hypotension - due to reduced blood volume weakness - sarcopenia bone demineralisation - osteopenia

Question 39

impact of exercise on muscle fibres

Answer 39

increase in size - hypertrophy increase in strength increase in endurance not the number of muscle fibres which increases but their size following increase in size, number of myofibrils, sarcomeres and nuclei also increase alongside number of blood vessels, mitochondria and connective tissue in relation the fibres themselves gives greater contractile strength and better O2 supply accelerates post exercise recovery and healing

Question 40

when do number of muscle fibres decrease

Answer 40

severe atrophy due to inactivity or paralysis

Question 41

affect of ageing on NMJs

Answer 41

surface area of NMJs decreases and so APs in the neurons stimulate APs in the fibre at slower rate and so less APs are generated

Question 42

affect of ageing on motorneurons

Answer 42

number of motorneurons present decreases so some fibres lose their innervation as the neuron has died - leads to another branch taking the role of innervating those muscle fibres - more muscle fibres being innervated by less nerve branches - overall decrease in motor units and decreased ability to generate specific and precise muscle movements if fibres lose their nerve supply, fibres become unused and the muscle will atropy