Skeletal muscle function: Ageing and Disease (DMD) pt. 1&2 Flashcards
what are 3 main motor unit types?
Fast fatigueable (fast glycolytic), fast fatigue resistant (fast glycolytic oxidixing), and slow (slow oxidizing)
larger, faster muscle fibres fatigue more/less easily? smaller, slower muscle fibres?
larger faster fatigue easily smaller, slower are fatigue resistant
a diverse compisition of muscle fibres within a single muscles would suggest the function of that muscle to be….
Diverse! performing several different functions. Best example is extraocular muscles.
how does muscle wasting contribute to reduced QOL and survival
sarcopenia —> age related muscle wasting –>muscle atrophy/loss of muscle mass
same mechanism for cachexia (muscle wasting due to pathology, AIDS, sepsis, cancer, etc)
what is sarcopenia? who is most at risk? clinical signs? diagnostic approach?
age-associated loss of skeletal muscle mass and function due to multiple causes (endocrine, systemic inflammation, etc)
especially elderly patients with observed declines in physcial function or overall health.
Clinically, patients may be those who are bedridden, cannot independantly rise from a chair, or a gait speed less than 1m/s.
Follow up DEXA scan confirms diagnosis if appendicular lean/fat ratio is <2SD from young adult.
Diagnosis can be made if patient has demonstrated low muscle mass + either low muscle strength or low physical perofrmance.
muscle wasting is inevitable, what is the process driving this at the motor unit level?
age-related motor unit remodelling.
progressive denervation of Type II motor units (fast) and reinnervation with Type I motor units (slow)
as muscle mass decreases, there is an increase in [….] and […]
fat and connective tissue
which muscle fibre type are most succeptible to age-related degeneration/change?
Type II. (fast twitch fibres)
which processes precede muscle wasting?
- slowing of contraction, with impaired release and reuptake of calcium
- loss/death of motor neurons and decreased number/diameter of axons from motor neurons in ventral roots.
Type 2 fibres most susceptible –> prolonging contraction time
3.progressive demyelination of axons, slowing down nerve transmission with NMJ modification (wider end plate, longer nerve terminals but fewer side branches )
muscle wasting is inevitable, what can be done?
strength training has muscle strengthening benefits all the way up to death. Importantly, it can rebuild type II fibres!
which circulating hormones are implicated with changes in muscle strength and size with ageing?
decreases in IGF-1, GH and testosterone—>compromises effieicience of muscle regeneration/repair
what is the current consensus on IGF-1, GH, and testosterone for ageing men wishing to preserve strength and size of muscle?
Strategies unsuccesful. No evidence for positive, sustained impact on muscles function.
what are the features of duchenne muscular dystrophy? presentation? inheritence? outcome?
most common inherited (x linked recessive) childhood lethal disorder.
1 in 3 cases is result of new mutation.
typically not detectable at birth, begins around 3-6 yrs of age. gait becomes lordotic and waddling.
presents with proximal lower girdle weakness, calf hypertrophy (pseudo hypertrophy) and elevated creatine kinase.
typically succumb to cardiorespiratory failure by 20yrs unlress artificially ventilated.
what is the molecular cause of DMD?
mutation in dystrophin gene on Xp21—> deficiency in dystrophin expression
what are the features of Becker’s muscular dystrophy? presentation? inheritence? outcome?
very similar to DMD, but less severe. those afflicted may survive well into adulthood.
disease progresses slowly and affects all voluntary muscles. Limb and trunk muscles affected first.
what is the molecular basis for BMD?
abnormal dystrophin is partially effective, as opposed to DMD where frameshift mutation causes small unstable fragments of protein are made.
what is the physiological role of dystrophin?
found on cytoplasmic surface of plasma membrane.
structural role in stabilizing sarcolemma during muscular contraction., esp lengthening actions.
what is a good indication of contraction-induced injury in mechanism of muscle damage in MD?
force deficit
NB: serum CK levels are elevated in MD mice after running downhill. enormous amount of muscle breakdown going on (very gragile muscles).
what is one of the primary mediations for many of the effects of dystrophin on muscle tissue?
intracellular calcium.
increases
what is the seqence of tissue phases after skeletal muscle injury?
degeneration, inflammation, regeneration, fibrosis
what are potential treatment targets for DMD
what is the current gold standard for tx of DMD?
corticosteroids
but many adverse events associatied.
VB15 is an antiinflammatory and membrane stabilizer that could improve symtopms without sig side effects.
