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
muscles most often affected in myasthenia gravis
eyes, mouth, pharynx, proximal limb, shoulder girdle muscles
considerations for pregnant pts with myasthenia gravis
33% have exacerbation
the bebe may have transitory symptoms
myasthenia gravis exacerbating factors
- infection
- stress
- surgery
- electrolyte imbalances
- some meds
myasthenia gravis exacerbating factors
- infection
- stress
- surgery
- electrolyte imbalances
- some meds
treatment of myasthenia gravis
- anticholinesterases (pyridostigmine)
- immunosuppressants
- plasmapheresis
- thymemectomy
IV equivalent of 60 mg TID pyridostigmine
2 mg
this is very confusing to me but i simply do not care enough to figure it out
2 complications of myasthenia gravis
what do they both present with?
cholinergic crisis
myasthenic crisis
both present with weakness and resp failure
what causes cholinergic crisis
what are the symptoms
giving too much anticholinesterase
excessive salivation & tearing, diarrhea, bradycardia, miosis, weakness, resp failure
what causes myasthenic crisis?
symptoms?
underdosing anticholinesterase
ptosis, weakness, resp failure
what should you expect if a pt with myasthenia gravis takes their meds DOS?
increased vagal reflex, interferes with NMBs, inhibits plasma cholinesterase
what should you expect if your myasthenia gravis pt doesn’t take their meds DOS?
possible deterioration with advanced disease
~whatever that means~
electrolyte imbalances especially important to correct preop for pt with myasthenia gravis
hypokalemia - can potentiate muscle weakness
induction conisderations for pt with myasthenia gravis
- may have pharyngeal or laryngeal weakness
- aspiration risk
- RSI
induction considerations for pt with myasthenia gravis
- may have pharyngeal or laryngeal weakness
- aspiration risk
- RSI
preferred anesthetic technique for pts with myasthenia gravis
regional or local
anesthetic technique if GA is used for myasthenia gravis
inhalation induction can decrease muscle tone enough for intubation & avoid need for NMBs
postop consideration for myasthenia gravis
muscle strength may seem adequate in early recovery but deteriorate a few hours later
predictors for postop ventilation in myasthenia gravis pt
- transsternal thymectomy
- having disease > 6 yrs
- daily pyridostigmine dose > 750 mg
- COPD
- preop VC < 2.9 L
NMB considerations in myasthenia gravis
- 10-100x more sensitive to NDNMBs
- treated MG: resistant to succs
- untreated MG: sensitive to succs
i thought it was untreated they are resistant and treated they are sensitive but idk which is up and which is down at this point
consulted TC via pharm I notes and she said if MG is untreated, they’re resistant to succs and sensitive to NDNMBs
treated = sensitive to succs, resistant to NDNMBs
where should TOF be assessed in pt with myasthenia gravis
orbicularis oculi
may overestimate degree of relaxation but best place to avoid undetected residual weakness
antiarrhythmics that worsen myasthenic weakness
- quinidine
- procainamide
- beta blockers (systemic and ocular)
- calcium channel blockers
antibiotics that worsen myasthenic weakness
- aminoglycosides (gentamicin)
- quinolones (cipro, levofloxacin)
- macrolides (erythromicin, azithromycin)
couldnt think of a way to ask this and combining it all was too damn long BUT
quinine, Mg salts, and iodine contrasts worsen myasthenic weakness
who cares
how do anticholinesterases affect LAs
may impair hydrolysis of ester LAs and cause prolonged block
amide class is ok
what causes Lambert-Eaton Myasthenic Syndrome
- autoimmune
- usually with small cell carcinoma of bronchi
age and gender Lambert-Eaton Myasthenic Syndrome is common in
men 50-70 yrs old
goal of Lambert-Eaton Myasthenic Syndrome treatment
improve strength, decrease ANS deficits (plasmapheresis, steroids, IVIG, immunosuppressants, ¾-diaminopyridine)
when should Lambert-Eaton Myasthenic Syndrome be suspected?
pts with muscle weakness and suspected diagnosis of lung carcinoma
diagnosis to suspect in pts with muscle weakness and possible lung carcinoma
Lambert-Eaton Myasthenic Syndrome
patho of Lambert-Eaton Myasthenic Syndrome
- presynaptic calcium channels damaged by autoantibodies
- reduced calcium-mediated exocytosis of ACh at NMJ
patho difference in myasthenia gravis vs lambert eaton myasthenic syndrome
LEMS - postjunctinoal AChRs unaffected
MG - postjunctional AChRs decreased
what disease is simular to botulism or mag tocxicity
Lambert-Eaton Myasthenic Syndrome
main symptoms of Lambert-Eaton Myasthenic Syndrome
- muscle weakness
- fatigue
- hyporeflexia
- proximal limb muscle aches
s/s ANS dysfunction with Lambert-Eaton Myasthenic Syndrome
orthostatic hypotension
impaired gastric motility
urinary retention
NMB considerations with Lambert-Eaton Myasthenic Syndrome
very sensitive to both succs and non-depolarizers
can use volatiles alone for tracheal relaxation
important pre-op discussion to have with a pt with Lambert-Eaton Myasthenic Syndrome
may need postop ventilation
and also prob all these damn diseases
what is true about all “myotonias”
all have inability of skeletal muscles to relax after stimulation (chemical or physical)
typical age of myotonic dystrophy onset
20-30 yrs
patho of myotonic dystrophy
skeletal muscles are hypotonic, dystrophic, and weak yet persistently contract
what is myotonia?
persistent contracture of muscle after stimulation
meds used to treat myotonic contractures
phenytoin, procainamide, tocainamide
how is muscle weakness assoc. with myotonic dystrophy treated?
it isnt :(
T/F - NDNMBs help with myotonic dystrophy symptoms
nope
s/s myotonic dystrophy
- hypoplastic, weak skeletal muscles of neck and face
- sleep apnea
- v sleepy (aka hypersomnolence)
- conduction defects
- intestinal hypomotility
conduction defects seen in myotonic dystrophy
- 1st degree AV block common
- bradycardia
- A fib/flutter
respiratory complications of myotonic dystrophy
pharyngeal/respiratory muscle weakness
restrictive-type disease
what general complication of anesthesia/surgery should def be avoided in pts with myotonic dystrophy
hypothermia - makes contractions worse
pre-op intervention for myotonic dystrophy
EKG
NMB use in myotonic dystrophy
avoid succs
NDNMBs are ok but recognize muscle wasting
what is duchenne’s muscular dystrophy (DMD)?
X-linked recessive progressive, painless degeneration and necrosis of muscle fibers
infiltration of fat and fibrous tissue in muscle
muscles affected first in DMD
pelvic girdle and muscles of thigh or calf depending on which slide you look at
:)
common age of presentation for DMD
2-6 yrs old
cardiac complications of DMD
cardiomyopathy
mitral regurg
ventricular dysrhythmias
EKG changes you might see in pt with DMD
tall R waves
deep Q waves
ideal anesthetic plan for DMD pt
local or regional
consider TIVA over GA
chronic med use in DMD that may need to be addressed intra op
plz reword my brain hurts
steroids
why is it v important to carefully titrate fluids in pts with DMD
CHF risk
why might you consider an NG tube in a pt with DMD
aspiration risk
what is the most chronic inflammatory disease in adults
rheumatoid arthritis
possible etiologies of RA
genetic
environmental
autoimmune (circulating autoantibodies in 70-80%)
joints typically affected in RA
PIP/MCP joints of hands and feet
when might an RA pt be on TNF inhibitors
systemic involvement
what is Felty’s syndrome
RA, splenomegaly, neutropenia
CV complications of RA
aortic or mitral valve regurg
pericardial effusion/inflammation
most common peripheral neuropathy in RA pts
carpal tunnel
musculoskeletal symptoms in RA pts
- dislocation and dissolution of skeletal structures
- deformed joints with no stability and minimal or no ROM
- severe pain
- crippling joint deformities
random s/s in RA pts
- constant low-grade fever
- photosensitivity
- muscle aches
- mucosal ulcers
- poor circulation
- pleural inflammation
- fatigue
- loss of appetite
most important joints involved in RA
TMJ
cricoarytenoids
atlantoaxial joint
what should you suspect in RA pt with hoarse voice?
swollen/inflamed cricoarytenoids
s/s c spine involvement in RA
limited neck movement
severe laryngeal deviation
most common site of c spine involvement in RA pts
C1-C2
20-40% have atlantoaxial subluxation
things about RA pts that makes careful positioning super important
osteopenic
steroid use
common med hx in RA pts
NSAIDs
steroids
methotrexate
TNF inhibitors
post-extubation complications to watch for in RA pts
laryngeal edema
stridor
pre-op consideration for RA pts with advanced disease
c-spine xray
RA + dry eyes =
sjogren’s syndrome
who gives a single shit*
*not me
