week 6 - ageing and degeneration Flashcards
functions of musculoskeletal system
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
impact of ageing on body
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
generic processes with ageing
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
MSK ageing syndromes
osteoporosis - bones
osteoarthritis - joints
sarcopenia - muscle
ageing within articular cartilage
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
osteoarthritis pathogenesis
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
bone ageing
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
hormonal changes in bone ageing
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
bone remodelling
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
risk factors for osteoporosis
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
diagnosis of osteoporosis
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
fragility fractures
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
prevention of osteoporosis
maximise peak bone mass: regular weight bearing exercise healthy diet sufficient vit D avoid smoking alcohol in moderation
treatment of osteoporosis
antiresorptive - reduces bone turnover by inhibiting osteoclast activity:
bisphosphonates
denosumab
raloxifene
hormone replacement therapy
anabolic - stimulates bone formation:
teriparatide - stimulates osteoblast activity
sarcopenia
progressive and generalised skeletal muscle disorder that is associated with increased likelihood of adverse outcomes including falls, fractures, physical disability and mortality
severe sarcopenia
when all 3 criteria met:
low muscle strength
low muscle quality or quantity
low physical performance
causes of primary and secondary sarcopenia
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)
diagnosis of sarcopenia
muscle function: handgrip strength chair stand strength usual gait speed timed up and go muscle mass: CT/MRI DXA
treatment of sarcopenia
no pharmacological therapies yet
resistance and aerobic exercise
attention to nutrition with increased protein intake - evidence less consistent
vitamin d supplementation in deficient patients
consequences of MSK ageing
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
factors influencing birth rate
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
factors affecting death rate
war accessibility and quality of healthcare droughts famine natural disasters vaccinations screening
epidemiology
the science and practice which describes and explains disease patterns in populations
difference between incidence and prevalence
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
functional ability
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
chronic musculoskeletal impact on quality of life
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
affect of freefall conditions in space
zero gravity mimics some of the effects of ageing
main cause of preventable falls in elderly
low muscle strength
falls are the main cause of accidental death in elderly
describe the components of body mass in a young person
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
factors impacting muscle and bone mass
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
function of inorganic and organic component of bone
i - hydroxyapatite crystals resist compression
o - collagen resists stretching
role of PTH, vitamin D and calcitonin in bone remodelling
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
what can disturb the balance of growth/breakdown of bone remodelling
endocrine factors eg menopause
diet and lifestyle
mechanical loading - exercise to promote
physical consequences of prolonged space flight
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
impact of zero gravity on bone mass
spaceflight induces loss of bone due to increased bone resorption and decreased bone formation
solutions for reduced bone mass after spaceflight
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
restricting body mass loss in space
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
effects of returnign to earth
hypotension - due to reduced blood volume
weakness - sarcopenia
bone demineralisation - osteopenia
impact of exercise on muscle fibres
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
when do number of muscle fibres decrease
severe atrophy due to inactivity or paralysis
affect of ageing on NMJs
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
affect of ageing on motorneurons
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
