Exam 3 - NMJ cont'd/Spinal Circulation Flashcards
Describe the normal adult nACh receptors?
- Have 5 domains: alpha and alpha 1 (binding); delta, beta, and epsilon
- High conductance: ions move through very quickly
- Activation is very brief
- Only at the NMJ
Describe the fetal or immature nACh receptors?
- Have a gamma domain instead of an epsilon domain
- Can be expressed on the muscle cell away from the NMJ
- Have a slower ion conductance and small strength of depolarization
- Stay open for a longer period of time
Describe the structure and location of alpha 7 nACh receptors?
- Have 5 alpha 7 binding domains
- Found within the CNS
Describe the effect of succinylcholine on immature nACh receptors?
The immature nACh are already open much longer at baseline, with the addition of succinylcholine the receptors are open for a very prolonged amount of time leading to hemorrhage of potassium.
Describe how the body responds with someone who has dysfunction of skeletal muscles?
The brain sends a signal to the muscle to contract, but it does not reciveve a confirmation that the muscle did contract (because it can’t or the signal is interrupted).
The body responds by expressing more nACh receptors, specifically the fetal nACh receptor.
This causes fetal nACh receptors to populate along the length of the muscle instead of just at the NMJ.
Why should we be concerned when giving succinylcholine to a person who has a skeletal muscle disorder?
Because they express more fetal nACh receptors and they are not contained at the NMJ, administration of succinylcholine will cause hemmorhaging of K+ which could lead to V fib.
What are the Junctional, Perijunctional, and Postjunctional areas?
- Junctional - the part of the muscle directly intact with the neuromuscular junction
- Perijunctional - the part of the muscle outside/around the junctional area
- Postjunctional - the area away from the junctional area, down the muscle fiber
Describe how electrodes can generate an action potential in a muscle?
Electrodes send electrons along the outside of the motor neuron making the outside of cell negative. If both the outside and inside of the neuron are the same charge, the cell is depolarized and an action potential is produced.
Fast Na+ channels are voltage gated, they dont care how the voltage is changed. When polarity is removed, the channels are triggered to open.
What is a supramaximal stimulus?
A stimulus that causes a stong enough depolarization to activate all of the motor neurons in a skeletal muscle.
Important to have a baseline supramaximal stimulus to accurately detect changes in motor response/function of a paralytic.
What is the frequency of stimulus during a TOF?
2 Hz over 2 seconds (4 twitches)
Hz= per second
What muscle group does the ulnar nerve inneravate? What does stimulation of these muscles cause?
- Adductor Pollicis
- Thumb moves forward, pinky moves in
Where are the alternatives for neuromuscular monitoring besides the ulnar nerve?
- Opthalmic branch of the facial nerve (innervates orbicularis oculi)
- Peroneal nerve
- Posterior tibal nerve
Describe the onset and duration of non-depolarizing muscle relaxants?
- Onset: 2-3 minutes
- Duration: Can be minutes to hours
Describe the onset and duration of depolarizing muscle relaxants?
- Onset: very fast, less than 1 minute
- Duration: Only a few minutes
Used because it is cheap, can be given IM
How is the TOF ratio derived? What does the ratio mean?
B/A, where B is the strength of the fourth twitch and A is the strength of the first twitch
When there is a large difference between B/A = smaller number = more paralyzed
When there is a smaller difference between B/A = larger number = closer to baseline
As the patient become less paralyzed, the TOF approaches 1.0
Why do NDMR cause return of twitches in stages with the first being the stongest?
They bind to nACh receptors as well as Alpha-3-Beta-2 ACh autoreceptors on the presynaptic neuron. The neuronal ACh autoreceptors allow Na+ and Ca++ influx which leads to replacement of VP-2 vesicles by VP-1 vesicles. NDMR inhibit this process which causes less ACh to be released with each stimulus which makes each muscle contraction weaker with every stimulus.
Why do DMR result in equal contractions with every stimulus?
Succinycholine does not inhibit the neuronal ACh autoreceptors, so there is plenty of ACh to respond to each stimulus resulting in equal strength of each stimulus.
Describe L-type Ca++ function on the neuron?
They a supplementary to p-type calcium channels
They function faster the cardiac L type calcium channels
They are not required for normal muscle function
A L-type antagonist can calm down the neuron
Describe the sensitivity to paralytics in different muscle groups? How does this effect return of muscle function?
- Less important muscles are more sensitive to paralytics because they have fewer NMJ
- More important muscles like the diaphragm are less sensitve because they have many NMJ and a robust number or receptors
- The more important muscles with more receptors will have return of function first
What type of muscle is the diaphragm? What nerve controls this? Where is this nerve originating from?
- Skeletal muscle
- Phrenic nerve
- C3, C4, C5
“C3 C4 C5 keep the diaphragm alive”
What number of receptors are needed to block each twitch in a TOF?
When does head lift rerurn?
- 4th twitch disappears when ~80% of nACh-R are blocked
- 3rd twitch disappears when ~85% of nACh-R are blocked
- 2nd twitch disappears when ~90% of nACh-R are blocked
- All twitches disappear when ~95% of nACh-R are blocked
- Head lift returns when ~70% nACh-R blocked
How much voltage should the nerve stimulator be set to? What is voltage and current?
50-80 mA
Voltage is the amount of force needed to push current (electrons)
The current is the rate of flow of the electrons measured in mA
What may occur with succinylcholine administration in patients with severe muscular disease?
- Hemmorhaging of K+
- Contraction of muscle due to the influx of Ca++ via nACh-R that are overexpressed on the muscle
What is the side effect on the eyes with depolarizing muscle relaxants?
Increased occular pressure
Occular muscles are innervated by multiple neurons which can lead to contraction of the occular muscles which increases the pressure. This is due to Ca++ influx in the nACh-R
Describe the role of GABA and Glycine in the spinal cord?
They are both inhibitory
GABA works by controlling Cl- permeability
Supresses the CNS
Inhibition of GABA or glycine = CNS overactivity
Describe ACh role in the CNS? Describe how it can be inhibited?
- Increases awareness
- Primarily controlled by mACh-R
- Can be inhibited by antimuscarincs like benadryl
Describe how we can increase ACh to increase someones awareness? What disease can this be used in?
By giving acetylcholinesterase inhibitors we can increase the amount of ACh and increase awareness if they cross the BBB
Used for treatment of Alzheimers
What are side effects of acetylcholinesterase inhibitors?
- Increased awareness
- Decrease in HR
- Increase in mucous production from glands
Describe histamine and glutamate as neurotransmitters in the CNS?
- Histamine - increases alertness (very similar to mACh-R)
- Glutamate - Increases CNS activity
-In meth, they have too much glutamate and can “burn out” and damage brain tissue
Describe dopamine as a neurotransmitter in the CNS? What disease displays a disorder in dopamine function?
- Pleasure chemical
- Potent motor inhibitor
- Parkinson’s cause decrease in dopamine = overactive nervous system (shaking)
Describe norepinephrine’s role as a neurotransmitter in the CNS? What drugs increase the amount of norepinephrine?
- Increases awareness
- SNRI increase NE and increase awareness and can aid in pain control