Musculoskeletal Disease Flashcards
skeletal muscle has what type of control and what type of characteristics?
- voluntary control
- striated
smooth muscle has what type of control and what type of characteristics?
where is it located?
- involuntary autonomic control
- nonstriated
- located in most internal organs (not heart)
cardiac muscle has what type of control and what type of characteristics?
- autonomic nervous system - its the intrinsic pacemaker
- striated
the generation of muscular force is dependent on what two things?
- intracellular Ca
- activation of actin and myosin filaments
where is skeletal muscle found?
- tongue and soft palate
- extrinsic eye muscles
- muscles that move the scalp
- all muscles attached to the skeleton
- pharynx
- upper 1/3 of esophagus
- lips *
- anus*
**serve as sphincters
what innervates skeletal muscles?
myelinated efferent motor nerve fibers
“alpha motor neurons”
muscle divides into branches and ends on individual muscle cells called what?
“muscle fibers”
what is one “motor unit” composed of?
1 motor neuron + all fibers in it
T/F: when a motor nerve fires, all fibers in the motor unit contract at the same time
true
normal neuromuscular transmission begins with what?
an action potential
the action potential reaches the nerve terminal and activates what?
the calcium channel
as an action potential comes down and activates the ion channels, what NT is released into the synaptic cleft?
acetylcholine
ACh that is released into the synaptic cleft bind to what receptors?
where are these located?
- bind to ACh receptors - obvi
- muscle plasma membrane
after ACh receptors are activated, what two things happen?
- ACh receptors open and allow Na+ to enter into the muscle
- rapid decline in ACh levels
what is the sequence of events after the ACh receptors open?
- Na+ into muscle generating action potential
- voltage-gated Na+ channels open and allow more Na+ into cell
- action potential leads to muscle contraction
what are the two causes of the rapid decline in ACh levels?
- ACh diffusion
- ACh deactivation by AChE within the synaptic cleft
~this prevents multiple reactivation of ACh receptors
how many ACh vesicles are released with each nerve impluse?
150-200
each ACh vessicle (quanta) has how many molecules of ACh?
10,000
what two types of antibiotics inhibit ACh release?
aminoglycosides
polymixin
how does Lambert Eaton Syndrome, associated with small cell carcinoma in the lungs, impact ACh release?
what other impact does it have regarding muscle action potential?
- decreases ACh release
- autoimmune derangement in presynaptic Ca2+ channels
how does botulinum toxin impact ACh?
decreases release
how does Mg impact ACh?
- Mg competes with Ca2+ at the voltage-gated channels
- decrease ACh release
how do calcium channel blockers impact ACh release?
block Ca2+ conductance through “slow” (L) channels in heart
decreased calcium = decreased ACh release
each neuromuscular junction has how many nicotinic ACh receptor sites?
estimated 50 million
where are ACh receptors located?
where are they made?
- located at crests of motor endplate junctional folds
- made in the muscle cells → pushed to the endplate membrane, junctional face protrudes a bit
T/F: activation of postjunctional receptors requires ACh binding at both of the alpha subunits
true
~must be simultaneous binding~
what happens once both alpha-subunits are occupied?
- cation channel opens →
- increased conductance to cations (especially Na+) =
- a net depolarizing potential (EPP)
what happens to the ACh receptor after an ACh molecule leaves?
channel closes →
current stops →
membrane resets or repolarizes
what determines whether ACh or our muscle relaxants has an effect?
~pls reword
dependent on concentration of ACh and concentration/binding properties of the antagonist
examples of drugs that block the ACh receptors
curare-like muscle relaxants
- vecuronim
- pancuronium
- cisatracurium
- rocuronium
and like all the other muscle relaxants…
examples of drugs that inactivate acetylcholinesterase
muscle relaxant reversal agents - compete with ACh for a subunit binding sites
- neostigmine
- edrophonium
- pyridostigmine
how do ACh reversal agents work?
- muscle relaxant reversal agents - compete with ACh for a subunit binding sites
- ACh not hydrolyzed so it increases quantity of ACh at synapse
what type of receptors are the prejunctional receptors?
cholinergic
what is thought to be the function of prejunctional receptors?
enhance neurotransmitter movement and release
what is seen from antagonist effects at the prejunctional area?
decrease in release of ACh
- can see a FADE on train-of-four*
- **Fade (with tetany and train of four) may be reflecting the blockade of prejunctional receptors by the NDMR and ACh release is not fast enough to keep up with rapid stimulation
MOA of AChE
- rapidly hydrolyzes ACh to choline + acetate in the junctional cleft
- choline goes back into prejunctional nerve terminal to make new Ach
cause God was the first recycler :)
how do muscle relaxant reversal agents - anticholinesterases (neostigmine) work?
- inhibits breakdown of ACh
- thus increasing the amount of ACh at the NMJ
- ACh antagonizes muscle relaxant
- transmission restored
what enzyme hydrolyzes ACh, metabolizes ester LAs, and SCh?
pseudocholinesterase
tell me about muscles in little uterus babies?
- no muscle innervation in utero
- muscle cells have extrajunctional receptors over the whole muscle cell
(yAChR and alpha7 subunits)
what age do muscle nerves become fully mature?
what receptors are seen/not seen at this point?
- 2 years
- ACh receptors only in neuromuscular junction
- extrajunctional receptors disappear from peripheral part of muscle
what occurs to muscle receptors if neural activity is decreased or removed?
- extrajunctional receptors formed
- muscle goes back to fetal like synthesis of yAChR and alpha 7 receptors
- can develop within 48 hrs post injury
- can later return to normal
(stroke, spinal cord transection, burn, direct muscle damage, prolonged immobility)
how do extrajunctional receptors respond to non-depolarizing muscle relaxants?
- resistant to NDMR
- large doses required
how do extrajunctional receptors respond to succs?
considerations?
- more sensitive to SCh (and ACh)
- channel stays open - Na+ into cell and K+ out
***no Sux (even small doses) —dangerous hyper-K+
***hyper-K+ bc prolonged depolarization and too much K+ out
examples of patients with increased extrajunctional receptors
med considerations?
stroke, spinal cord transection, burn, direct muscle damage, prolonged immobility
no succs ever (potential hyperkalemia/death)
what is myasthenia gravis?
chronic disease
decreased number of working postsynaptic ACh receptors
causes of myasthenia gravis
- autoimmune: 80-85% have IgE antibodies
- thymus seems to play a role
what organ might be removed in a pt with myasthenia gravis
thymus (improves symptoms but not curative)
lol remember how isla got a freaking thymus transplant
T/F - pts with myasthenia gravis have cognitive dysfunction
false - only a motor disease
:(
hallmark of myasthenia gravis
generalized weakness that improves with rest
severity of myasthenia gravis symptoms
range from slight ptosis to resp failure
