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
How is our CNS activity affected by pH?
Acidity decreases CNS activity
Alkalinity increases CNS activity
What is the CO2 buffering system equation?
Describe the relationship between Ca++, H+, and albumin and their affect on CNS activity?
Both Ca++ and H+ ions are attracted to albumin due to it’s negative charge. The more H+ ions present, the more that are bound to albumin, and the less Ca++ can bind - leading to an increased plasma concentration of Ca++. When ECF Ca++ is increased, more Na+ leak channels are blocked leading to hyperpolarization of cells, decreased excitability, and supression of the CNS activity.
The opposite is true when H+ are low. This means more Ca++ is bound to albumin means lower ECF Ca+, leading to increased CNS activity.
Explain hyperventilation and hypoventilation and their effect of CNS activity?
- Hyperventilation = decreased CO2 = decreased H+ = alkalosis = more bound Ca++ = increase Na+ entry = CNS overactivity and seizures
- Hypoventilation = increased CO2 = increased H+ = acidosis = less bound Ca++ = less Na+ entry = CNS supression
What structure is noted by 5 below?
What is the name of the fissure that this artery runs in?
What percent of blood flow to the spinal cord flows from here?
- Anterior Spinal Artery
- Anterior Median Fissure
- 75% of Blood Flow
What structure is noted by 1 below?
How many of these are there?
How much of the spinal cord is perfused by these?
- Posterior Spinal Artery
- Two
- 25%
What 4 arteries feed the posterior spinal arteries?
- Vertebral Arteries
- Anterior Inferior Cerebellar Artery
- Posterior Inferior Cerebellar Artery
- Posterior segmental medullary arteries
What arteries feed the radicular arteries in the spinal cord? How many source arteries are there?
- Branches of the intercostal arteries
- One ertery per each rib (12 sets)
What structures are noted by 3 & 4 below?
What is another name for these?
How do they typically branch off the intercostal arteries?
- Anterior/Posterior Segmental Medullary Arteries
- Radicular/medullary/segmental Arteries
- Usually goes either goes to the anterior cord OR posterior cord, not to both
Describe the pattern of insertion of the radicular arteries?
Very irregular
Usually will have one radicular artery every 5-6 levels and it is either posterior or anterior
Varies from person to person
What is the indicated structure?
Coronal arteries
Why would injury to an artery in the cord be more damaging than one in the brain?
There is no circle of willis type collateral flow in the spinal column which will lead to damage if the arteries become compromised
How are spinal veins arranged?
They are located near the arteries
He did not elaborate on the spinal veins
What structure is noted by 5 below?
Where does it branch from?
Posterior Intercostal Artery
The thoracic aorta
What is 1 and 2 in the picture?
What does 2 sit on top of?
What levels are these found at?
How do they connect?
- Dorsal Branch
- Spinal branch
-Sits on dorsal root ganglia
-Feeds front or back as radicular arteries, varies with each person and does not always go all the way to the cord
What are numbers 3 and four?
- Anterior Radicular artery
- Posterior Radicular artery
What are numbers 1 and 2?
- Intercostal arteries
- Renal arteries
What should we be concerned about with aortic cross clamping?
- Where the clamping is occuring
- What structures are being affected
-cross clamping of the aorta prevents flow to the radicular arteries and can cause ischemia to the cord
What is the indicated structure?
Anterior spinal artery
What are the indicated structures?
Left and right anterior segmental medullary arteries
What is the indicated structure?
Posterior spinal artery
What is the indicated structure?
Posterior segmental medullary artery
How many anterior radicular arteries per areas of the spine?
- C-spine: 2
- T-spine: 2-3
- L-spine: 1-2
What structure is noted below?
Where does it branch from?
How much of the spinal circulation does it account for?
What level can you find this artery?
- Great Radicular Artery of Adamkiewicz
- Posterior intercostal artery
- 2/3 of the lower spinal circulation
- T10
-T9-T12 most people
-T5-L5 absolute range
What can happen if the aorta is cross clamped above the great radicular artery?
The anterior spinal artery is not being perfused below the clamp, which leads to ischemia to the dorsal horn of the cord leading to paralysis
What structure is noted by 8 below?
Great Radicular Artery of Adamkiewicz
What can cause an increase in pressure surrounding the spinal cord? What can this cause?
- Increase in CSF pressure caused by aortic cross clamping (can increase pressure by ~10mmHg or more)
- Can inhibit spinal blood flow
How can we treat or prevent excess CSF pressure in the spine and the problems it creates?
- Insert a drain
- Drugs that reduce inflammation
- Drugs that slow metabolic rate in the cord
Describe how restoring blood flow can cause damage after cross clamping?
Can cause reperfusion injury.
Ischemic tissue cant handle the sudden increase in O2 flow.
Oxygen is used to destroy things in the body by oxidation, very powerful.
Describe the sections of the spinocerebellar tracts and the information that they relay?
- Helps coordinate complex motor movements
- Anterior/ventral
-Measures the amount of activity in the dorsal horn and sends information to the cerebellum. - Posterior/dorsal
-Tendon and muscle spindle confirmation.
What tract does the dorsal/posterior spinocerebellar tract take?
- Dorsal spinocerebellar tract to inferior cerebellar peduncle
What tract does the ventral/anterior spinocerebellar tract take?
Ventral spinocerebellar tract to superior cerebellar peduncle
Describe pain threshold?
The ease or difficulty of eliciting a painful feeling
May be related to membrane potential
- Some people have higher threshold potentials and more pain can be tolerated before AP is sent
What is visceral pain?
Organ pain sent by the autonomic nervous system
Causes referred pain, poorly localized
What is parietal pain?
Connective tissue pain, direct conduction to the cord
Highly localized
What organs do not have visceral pain sensors?
Liver, lungs, and brain
Describe the pain felt with the appendix?
Visceral and parietal pain
Visceral pain routed to T10 level or umbilicus
Visceral does not have lateral inhibition
Describe referred pain in the heart?
Referred to left shoulder and arm
Does not go to right because the right heart is much less prone to ischemia
Where does stomach pain refer?
Refers higher than the organ, can be mistaken as a heart attack
Where does kidney pain refer?
The lower back
What are the 3 areas in the limbic system?
- Amygdala
- Hypothalamus
- Cingulate gyrus
What are the circled areas?
Amygdala
Name the organ circled here involved in the limbic system?
Hypothalamus
What is the black circled region?
Cingulate gyrus
This affects slow pain and not fast pain because it is buried deep in the brain
What sensory functions are sent via A alpha fibers?
- Skeletal muscle
- Muscle spindle
- Muscle tendon
What type of fiber is involved in lateral inhibition?
A beta fibers
What type of sensory information is sent via C fibers?
Tickle, nausea, aching, cold, warmth
What is the name of the ACh receptor on the neuron that NDMR bind to?
Alpha-3-beta-2 ACh autoreceptor
