Exam 3 Flashcards
Where does the cord transmit information from the periphery?
-Brainstem
-Cerebellum
-Brain
What is an efferent pathway?
-The sending portion of the CNS (Motor primarily; travels down the cord)
What is an afferent pathway?
-Receiving portion of the cord (sensory; travels up the cord)
In the cord, sensory information is primarily transmitted in which general area?
-dorsal with some anterolateral
(Just in case he asks)
On the powerpoint slide regarding spinal cord, what color are the afferent vs efferent pathways? What do they mean?
-Afferent (receiving sensory) is blue; travels up the cord
-Efferent (sending primarily motor) is red; travels down the cord
What are some sensors for afferent sensory pathways mentioned in lecture?
-Temperature sensors in skin
-Vibration
-Pain
What type of matter is “decision making?”
Gray matter
What is located in gray matter?
-Cell bodies
-Lots of synapses
What is a tract?
A bundle of axons within the CNS
What is another name for a bundle of axons outside the PNS?
Nerves
What is another name for the main descending pathway?
Pyramidal Tract
What kind of actions can take place from the pyramidal tract, per lecture?
-Moving an arm around
-Moving a leg around
What is the Extrapyramidal Tract responsible for?
- Accessory motor pathways
-Coordinate complex tasks
-Help modulate, control, and give us feedback on instructions received from the pyramidal tract
Between the pyramidal tract and the extrapyramidal tract, which one is voluntary? Which one is involuntary?
Pyramidal tract - Primarily voluntary; aware of actions
Extrapyramidal tract - No realization or knowledge of functioning; helps fine tune motor commands
Where are the pyramidal tracts located? What are the names of the two pyramidal tracts? Which is bigger?
Lateral corticospinal tract - Posteriobilateral cord, superficial to the dorsal horn, deep to the outer edge of the cord where sensory information is; bigger
Anterior corticospinal tract - Also two areas immediately bilateral to the anterior median fissure
What are the four names of the sections within the extrapyramidal tracts?
-Rubrospinal tracts (4; immediately anterior to each lateral corticospinal tract)
-Reticulospinal tracts (2; deep anterior median fissure, bilateral to the start of the fissure)
-Olivospinal tract (2; lateral to Vestibulospinal tract)
-Vestibulospinal tract (2; lateral to the most anterior part of the anterior median fissure)
What is the main ascending (afferent pathway)?
The dorsal column pathway
What things do the Dorsal column pathways do as described in lecture?
-Pressure sensors in skin
-Are you holding anything in your hands?
-Are your hands in the air?
-Touch
-Perception
Which afferent pathway does pain follow?
The Anterolateral system
What are the two parts of the anterolateral system?
-Lateral spinothalamic tract (2; bilateral, immediately lateral to the Olivospinal tract)
-Anterior spinothalamic tract (2; bilateral; immediately deep to the Olivospinal tract)
What is another name for the anterolateral system?
-Spinothalamic tract/pathway
What path does the anterolateral system/spinothalamic tract follow?
-Pain enters cord and ascends via afferent pathway of the anterolateral system –> Pain relayed through the Thalamus –> Pain signal goes to parietal cortex to get sorted out (Where is the bad pain coming from; how severe is it?)
What is the collective name for the different parts of the gray matter of the cord?
-Rexed’s Laminae
-(Pronounced “rex-ed” or “rexed” per daddy Schmidt)
Where is lamina I located? What is another name for it?
-The most dorsal part of the dorsal horn.
-Lamina Marginalis
What is the Lamina Marginalis known for, and which # lamina is it?
-Sending fast pain signals to the brain
-Lamina I
Is lamina I myelinated? If so, what type of mylenation?
-Yes
-A-delta fibers (make sure to know what delta looks like in case he puts it on a test; can’t copy and paste; feel free to fix)
What is the path that fast pain takes to reach the final afferent pathway toward the brain?
Sensor –> Root –> Rootlet –> Cord –> Lamina I/laminate marginalis synapse cell bodies –> Crosses over via Lamina X –> Ascends in anterolateral cord
Collectively, lamina II & III are called
Substantia Gelatinosa
What goes through the Substantia Gelatinosa, and what lamina are they?
-Slow pain conduction
Lamina II & III
Are Lamina II & III myelinated?
-No
-Type C fibers (nonmyelinated)
Which lamina does the Substantia Gelatinosa synapse with sometimes in regards to slow pain?
Lamina V
What is the route that slow pain takes to reach the final ascending pathway?
Receptor –> Nerve –> Posterior Root –> Posterior rootlet –> Dorsal horn –> Lamina II & III; sometimes V –> Crossover through Lamina X –> Anterolateral spinothalamic pathway
What do laminae I-VI have in common?
Mechanoreceptors relay information to the gray matter in the cord
(Take physical pressure & turn it into electrical energy)
When Schmidt said we have quite a few mechanoreceptors, what two examples did he give in regard to location?
-Hands
-Skin
In the spinal cord, where is Lamina VI?
Directly lateral to the posterior portion of the lamina X crossover pathway
Which lamina group is sensory?
I-VI
Which lamina group is motor?
VII-IX
Which lamina is for crossover?
Lamina X
What are the two ways for the cell bodies in the anterior horn to be activated?
-Motor center in brain
-Reflex arcs
What is the white matter called that has crossover in the cord?
Anterior white commissure
What is another name for Lamina VII? Is it sensory or motor?
-Intermediolateral nucleus
-Motor
What is typical of Lamina VIII?
-Lots of large motor neurons
Both afferent and efferent signals can go through which two structures?
Anterior white commissure & Lamina X (grey)
Extrapyramidal tracts are
Primarily accessory motor pathways
Spinocerebellar tracts are
Sensory tracts that send information from the spinal cord to cerebellum
What is another name for the dorsal column pathway?
DCML (Dorsal-column medial lemniscal system
What signals do the DCML send? Where is it?
-Major pressure/sensory signals; major touch sensitive pathway
-Sits in the dorsal part of the cord
What structure does the dorsal column pathway pass through to get to the brainstem?
Medial lemniscal
What does the anterolateral/spinothalmic tract conduct?
Pain signals
What is another name for the pyramidal tract?
Corticospinal tract
What gives the corticospinal tract its name?
Signals originates in cerebral cortex & passes through the spine on the way to talk to the skeletal muscle
Is the corticospinal tract afferent or efferent? Where do the signal originate?
Efferent - originates in cerebral cortex/motor cortex
The DCML takes care or most kinds of signals except what?
Pain
What kind of nerve fibers are involved in the DCML pathway?
Type A fibers
What kind of A fibers does the DCML pathway have?
Alpha, beta, gamma, delta; varies - various sensations get sent through various fibers
Per Schmidt, what kind of sensations go through the DCML?
-Pressure
-Vibration
-“sensory stuff”
What part of the body does the left side of the CNS take care of?
Right; vice versa
Where does crossover occur in the DCML pathway? What is the path?
-Medulla
Sensation –> Posterior rootlet –> Cord –> Some sensation stays within gray matter; others go to the DCML to go to the medulla/brain
Why does some sensory information stay in the gray matter in the cord?
-Lateral inhibition
-Modulation of activity in the cord
What relationship exists between the cord and the DCML?
The higher you are on the cord, the larger the pathway. (i.e. T11 may only have legs and a few other things, while in the cervical cord you may have BUE)
What part of the DCML sends sensory information from the lower part of the body? What’s an easy way to remember this per Schmidt?
-Fasciculus Gracilis
-Gracilis muscle is in the leg**
What part of the DCML sends sensory information from the upper part of the body?
-Fasciculus Cuneatus
Where on the cord does the Fasciculus Gracilis start, per Schmidt?
-L1 or T10
-Information from BLE
What part of the DCML pathway is the Fasciculus cuneatus located?
The most lateral part
What part of the DCML pathway is the Fasciculus gracilis located?
The most medial part
Is the DCML sensitive? What kind of changes can it detect?
-It is very sensitive.
-It can pick up very small pressure changes, i.e. tickles
On the slide where someone was tickled, what color was each feather tickling the foot and the hand?
Foot - blue
Hand - red
What lobe of the brain would a tickle sensation be sent to?
Parietal
If you were tickled on your foot with a feather, what would be the path the signal would take through the DCML?
Tickle –> Dorsal root –> Dorsal root ganglia –> Dorsal column (lowest point; start of Fasciculus gracilis) –> up the cord (Fasciculus Cuneatus joins mid trunk—> Medulla –> Medial lemniscus —> Through the thalamus (ventrobasal complex)–> Internal capsule –> Parietal lobe
Per Schmidt, what area of the Thalamus do tickle sensations go through?
Ventrobasal complex
What is the ventrobasal complex in charge of?
Sending info to the parietal lobe (it’s like a sorting hat)
Where is the internal capsule?
Just outside the thalamus
What is another name for the sensory cortex of the parietal lobe?
Postcentral gyrus
What part of the parietal lobe receives information from the BLE
Top
What part of the parietal lobe receives information from the trunk?
Mid-high
What part of the parietal lobe receives information from the BUE?
Mid-low
What part of the parietal lobe receives information from the face?
Bottom
If you have a stroke in the mid-low area of the parietal lobe, what would be the result?
“messed up sensations”
What kind of picture is used to describe areas of the body that the parietal lobe affects?
Homunculus; slide 27 lecture 5
How does the size of the area on the parietal lobe controlling a specific body part correlate to that body parts size?
It will be proportional; i.e., many more neurons(larger area) working with BLE than the tongue
If a blind person had a stroke in the mid-high parietal lobe, what would be the result? Why?
-They wouldn’t be able to read braille.
-Pressure sensors are in abundance in the hands, but the mid-high area of the parietal controls them.
What two areas of the body did Schmidt stress that we have lots of sensors?
Face, hands, and feet, but he stressed face and hands
Does the trunk have more or less sensors than the arms or legs?
Less sensors than BUE/BLE
Why are pyramidal tracts (the main motor tract) called Pyramidal?
The signal passes through the pyramids in the brain stem
What passes through the internal capsule?
-afferent signals (sensory)
-efferent signals (motor)
What % of motor function is controlled via the Primary Pyramidal tract?
80% (4/5ths)
What path does the Primary Pyramidal Tract take to get to the cell bodies in the anterior horn of the cord?
Signal originates in the motor cortex of the frontal lobe –> Internal capsule (right outside the thalamus) –> Brainstem (Pyramids of medulla; crossover here; AKA pyramidal decussation) –> Lateral corticospinal tracts –> Activation of motor neuron in the anterior horn of the spinal cord
Where are the pyramids of medulla located on the medulla?
Anterior, medial
-“At the very end” - per Schmidt
How are the pyramids of medulla oriented?
-“Crosshatched”
-Horizontal
(Think, it has to get to the other side! so it goes to the…..side).
Tyler-ism™
What is another name for the pyramids of medulla?
Medullary pyramids
What is the area within the medullary pyramids where crossover happens?
Pyramidal decussation
What are the up and down ridges on the medulla?
Pyramids
On the medulla, what is the area of horizontal strands of neurons between pyramids?
Pyramidal decussation
Does the midbrain have pyramids?
-No. Only the medulla has pyramids.
How much motor information does NOT crossover at any point?
2-3% “third motor pathway”
What % of motor information is sent via the Secondary motor pathway?
17%
What is another name for the secondary motor pathway?
Anterior corticospinal tract
Where does crossover happen in the primary motor pathway?
Medullary pyramid
Where does the secondary motor pathway cross over?
At the level of the cord where it has to talk to motor neurons (i.e. travels down same side of the cord where input is until it gets to the level of action, then crosses over)
In which motor pathway does crossover happen superiorly?
Primary motor tract
How many paths does pain follow? What do they have in common?
-Two
-Both relayed through the Spinothalamic or anterolateral tract (interchangeable terminology)
Which pathway does Fast pain take?
Lateral spinothalamic pathway
Which pathway does Slow pain take?
Anterior spinothalamic pathway
What is the main neurotransmitter for Fast pain? and what effect does it have?
Glutamate ; excitatory (fast to release and act)
What type of fibers does fast pain travel on?
A delta fibers (myelinated)
What type of fibers does slow pain travel on?
C fibers (unmyelinated)
What are the pain receptors called?
Nociceptors (free nerve endings)
Where does fast pain get sent to?
Parietal lobe
What does fast pain run parallel to?
DCMLS
In terms of localization, which one is better at localizing, fast pain vs slow pain?
Fast pain –> can tell exactly where injury occurred
Slow pain –> have general idea but can not identify where pain is coming from
Which lamina do slow pain synapse upon in the grey horn?
Lamina II, III & sometimes V
Where do pain pathways cross over to the other side of the cord?
Anterior White Commissure
What is the prefix that can be added to fast pain pathway? (think age)
Neospinothalamic Tract (neo = new)
What is the prefix that can be added to slow pain pathway? (think age)
Paleospinothalamic Tract (paleo = old)
What are the neurotransmitters for slow pain?
- Substance P (Main neurotransmitter)
- CGRP
- Glutamate (slower to act and to release)
Where does slow pain get routed to?
Most slow pain gets routed up to the brainstem or thalamus & not much further
What are a couple of sensors slow pain can be associated to?
Thermoreceptors/heat & vibration sensors
what does slow pain get involved with? (messes with your head)
Emotional centers (are near brainstem)
What is the sloth of tissue at the top of the brain stem where slow pain ends called?
Reticular formation
What is the function of the Vestibulospinal tract? (extrapyramidal)
Maintains balance & eye muscle fixation
What does the reticulospinal tract maintain? (extrapyramidal)
Maintains muscle tone in skeletal muscle
What does the Rubrospinal tract aid in? (extrapyramidal)
Voluntary movement (similar to cerebellum)
The descending pain suppression system is __ in nature & responds to pain
inhibitory
What are the two initial neurons in the DIC? (1st order)
Periaqueductal Gray (near cerebral aqueduct) & Periventricular nucleus (near ventricle)
When the initial neurons are excited what do they release? (1st Order)
Enkephalin
Where does the Enkephalin from first order get released to?
Raphe Magnus Nucleus (RMN –> found in the middle of pons)
What does the RMN release? (2nd order)
Serotonin (5-HT)
Where does 5-HT release at?
Dorsal horn of spinal cord
What does 5-HT act on? and what is released?
Enkephalin neuron ; Enkephalin
What does enkephalin do once its released into the cord?
Binds to enkephalin receptors on the Nociceptor & on the ascending pain receptor pathway & inhibits both reducing pain sensation
In first order DIC is enkephalin inhibitory or excitatory?
Excitatory (excites RMN)
In the spinal cord is enkephalin inhibitory or excitatory?
Inhibitory (binds and shuts down pain receptors)
What is an Enkephalin?
Endogenous morphine analog (all opioid receptors are enkephalin receptors)
In patients with chronic pain, what happens with glutamate receptors?
They get up regulated & system gets more difficult to inhibit
What does a crush, cut, or stab do to a nociceptor?
Depolarizes
If someone is acidotic, what happens to K levels?
Increased
With increased K levels, what happens to nociceptors?
They can depolarize and cause pain
Are patients that are acidotic and need dialysis with high K pain seekers?
No - higher sensitivity to pain due to high K
Why does histamine cause pain?
Inflammation in tissue
What is the difference between serotonin at the cord and in the periphery?
Cord - inhibitory
Periphery - depolarizes nociceptors/painful
What neurotransmitter related to skeletal muscle movement also can result in pain if in the periphery?
ACh
Are prostaglandins painful?
Not by themselves, but they can augment other pain signals and make it worse.
What will inhibiting prostaglandin formation do?
Decrease pain sensitivity
What does the Vestibulospinal tract maintain?
Maintains balance & eye muscle fixation
What does the Reticulospinal tract maintain?
Maintenance of muscle tone skeletal muscle
What does the Rubrospinal tract aid in?
Modulation of voluntary movement (similar to Cerebellum)
What are opioid receptors?
Enkephalin receptors
How do opioid receptors work?
GCPRs, that are bound to K channels –> when activated increase permeability to K –> making them more difficult to excite –> reduced pain signal
Where are opioid receptors found?
on both nociceptor & ascending anterolateral pathway
How do alpha-2 receptor agonists in the nociceptor & ascending anterolater pathway?
Similar to opioid receptors, GCPRs, connected to K channel, activation increases permeability to K –> reduced pain signal
what are the benefits of alpha-2 receptors agonists?
Pain suppression & relaxation in CNS without the euphoria
What are the three alpha-2 agonist mentioned in class from least specific to most specific?
Xylazine, Clonidine & Dexmedetomidine
How do Volatile anesthetics work?
increase K conductance at pain receptors & in CNS –> reduces consciousness & pain
What effect does Nitric Oxide Synthase (NOS) have at the nociceptor?
Increases sensitivity of pain at synapse
How does OTC magnesium help reduce chronic pain?
Magnesium reduces NDMA-R activity by keeping channel from being opened
How does Cox2 affect the pain pathway?
it is expressed in the nociceptor in response to pain & produces prostaglandins –> increasing the sensitivity to painful stimuli on both nociceptor & ascending pain pathway
When we are born, what type of nACh-Rs do we have?
Immature (fetal) nACh-R
If the muscle is not contracting or confirmation of contraction does not get back to the brain, what is the compensation mechanism?
The skeletal muscle will increase nACh-Rs, but they are mostly fetal nACh-Rs and are placed all over the skeletal muscle not just NMJ
What is the difference between a immature nACh-R and an Adult nACh-R?
- fetal nACh-R: slow ion conductance & stay open for a longer period of time
adult nACh-R: high conductance, active for a short period of time
What are the binding sites in a neuronal nACh-R?
it has 5 a7 binding sites, found in neuronal muscle
What affect does succs have on immature nACh-Rs?
it has even greater affect –> really long period of time they stay open
What is the junctional area?
Area where nACh-R are found, NMJ
What is the Peri-junctional area?
area right outside junction
What is the post-junctional area?
area away from junctional area
Where do you place electrodes to see what affects paralytics are having?
Motor neurons
What do the electrodes produce when a current is applied?
Action Potential (depolarization)
If you run a current on a motor neuron and see a big contraction, what does that tell you in regards to your paralytic?
The block is NOT deep enough
If you run a current on a motor neuron and dont see a contraction, what does that tell you in regards to your paralytic?
The block is deep
What kind of current runs through electrodes? and what affect does this have on the cell membrane?
Electrons runs through the current & generate an action potential by making outside of cell negative & eliminating charge difference (no more polarity)
What is the term for a stimulus strong enough to recruit all underlying motor neurons?
Supramaximal Stimuli
What is a single twitch setting on a nerve stimulator?
One impulse & see what happens
What is the train of four?
repetitive stimulation - 2Hz at 2secs –> two impulses at 1 second x2 = 4 total switches
In which NMB agent would we see differences in magnitude of responses on a chart?
NDMR
In which NMB agent would we see similar magnitude of responses on a chart?
Depolarizing muscle relaxant
Describe tetanic stimulation
high frequency stimulation for a short period of time
Describe Post-tetanic count (PTC)
impulses muscle generates after a period of tetanic contraction
Describe Double Burst Stimulation
high frequency stimulation for a couple seconds, take a break, high frequency stimulation for a couple seconds
Where is the most common place to place electrodes to test NMB agents?
Ulnar nerve
The Ulnar nerve stimulates which muscle?
Adductor Pollicis
Where are other places to place electrodes to test NMB agents?
peroneal nerve, Ophthalmic branch of facial nerve, & posterior tibial nerve
What is the typical onset for NDMR & Succs?
NDMR - a few minutes
Succs - fast onset
Why is Succs popular in use?
Fast onset, cheap & short acting
If we were to graph the recovery from a NDMR, what would the graph look like?
difference in amplitude, with the first twitch amplitude being the highest and gradually declining in an exponential manner
If we were to graph the recovery from a Depolarizing muscle relaxant, what would the graph look like?
Equal amplitude in each twitch gradually increasing until recovery
What is the TOF ratio for NDMR?
a fraction (B/A)
- B = strength of contraction of last twitch
- A = strength of contraction of first twitch
Early on in the recovery from a NDMR, what would the TOF ratio look like
<1, very small
Near full recovery from a NDMR, what would the TOF ratio look like?
gets close to 1
What would you expect the depolarizing muscular blocker TOF ratio to look like?
very close to 1
What are ACh-R found on the motor neuron called?
Aphla3-Beta2 ACh-R
What is another name for ACh-Rs found on the motor neuron?
Autoreceptors
how do alpha-3 Beta-2 ACh-R (autoreceptors) get activated?
ACh dumped into synapse feeds back & binds to autoreceptors
What is the current that comes in through autoreceptors?
Na & some Ca
What purpose does the current that comes in through the autoreceptors serve?
move forward VP-1 ACh into VP-2 ready position
What affect do NDMR have on autoreceptors?
They bind to ACh autoreceptors and block it, preventing influx current –> leading to less VP-1 moving into the VP-2 ready position –> weaker contraction with repeated stimulation in TOF
What affect do depolarizing muscle relaxant have on autoreceptors?
They bind to ACh autoreceptors & elict depolarization –> influx of current –> VP-1 gets moved into VP-2 –> equal amplitude of contraction in repeated stimulation in TOF
How is succs degraded?
by plasma cholinesterase
How many ACh are required to activate autoreceptors on motor neuron?
3 must bind
What is the Artery located in the Anterior median fissure?
Anterior Spinal Artery
How many Posterior spinal arteries do we have? & why?
2 ; posterior median fissure not deep enough house a large artery
Where do the Posterior spinal arteries obtain their blood from?
Vetebral arteries (found in neck), Cerebellar Arteries (anterior inferior & posterior inferior cerebellar arteries) & Radicular arteries
Where do Radicular arteries branch from? and what do they feed into?
Intercostal Arteries –> anterior & posterior spinal arteries
What is the feeding pattern look like for Radicular arteries?
Irregular, normally have one radicular artery feeding into front or back & can come from either side
What are other terms for Radicular arteries?
Medullary arteries, Segmental arteries & a combination of both –> Segmental medullary artery
What are the arteries on the outer surface of the cord?
Coronal arteries
Do the spinal cord arteries have collaboration?
No, loss of an artery will induce damage
How does the vein setup differ from the artery set up?
A posterior spinal vein is found in the middle
At every level we should have __ coming off the dorsal branch of the intercostal arteries
Spinal branch
What are the intercostal arteries responsible for?
keeping the rib cage perfused
What supplies the small intestines with blood?
Mesenteric artery
What are we concerned about when it comes to having to repair Triple As?
Clamping Aorta & preventing perfusion to spinal cord
What is the main source of blood supply for Radicular arteries?
Aorta
How much blood is supplied by the Anterior spinal artery & the posterior spinal artery?
Anterior spinal artery - 75%
Posterior spinal arteries combined - 25%
- about 12.5% each
Loss of which spinal artery would be detrimental?
Anterior spinal artery (supplies 75% of the blood to spinal cord)
In a typical patient, how many Anterior Feed arteries come in from the neck, thorax, & lumbar?
Neck - 2
Thorax - 2-3
Lumbar - 1-2
Which vessel supplies 2/3 of arterial blood to lower part of spinal circulation?
The Great Radicular Artery (GRA)
- Artery of Adamkiewicz
Where does the GRA typically enter from?
Left side
Where can the GRA typically be located, what are the ranges & what is the Absolute rage?
Normally Located T-10
- Can range between T-9 to T-12
- Absolute range is T-5 to L-5
Cross clamping below GRA, what is the concern?
There is no concern as GRA is still being supplied
Cross clamping above GRA, what is the concern?
Concern for paralysis or loss of motor function of lower body due to no blood supply from GRA
- may see some sensory dysfunction but main concern is motor
How is cross clamping above GRA avoided?
Using imaging
- that is if time permits, may have to clamp in an emergency
What is the ideal origin of the GRA, for to originate high or low?
High –> more room to clamp below –> safer
(if it originates low it is much easier to obstruct)
What is the top way that leads to an increase in CSF pressure in the spinal cord?
Cross clamping in Aorta
On average aortic cross clamping increases CSF pressure by how much?
10mmHg
What is normal ICP?
10mmHg
How can you get around an increase in CSF pressure caused by aortic cross clamping?
use a drain to decrease CSF & decrease perfusion pressure
Prolonged ischemia (cross clamping) can lead to cell death, what are somethings that can be done to slow this process?
Anything that reduces inflammation & drugs that slow down metabolic rate
Sudden restoration of blood flow in a vessel can cause what?
Ischemic Re-perfusion
What happens in Ischemic Re-perfusion?
massive return of blood to which tissue can not handle at once (overloaded with oxygen)
What defends against oxygen induced damage?
Antioxidants
What can you do to prevent ischemic re-perfusion?
slowly return blood flow
What does the body use to destroy stuff?
Oxygen (oxidation)
What are the tracts that send information to Cerebellum that aid in complicated movements?
Spinocerebellar Tracts
What are the two Spinocerebellar tracts?
Anterior Spinocerebellar tract & Posterior Spinocerebellar tract
What kind of information does the Anterior spinocerebellar tract send & where does it send it to?
information regarding activity in anterior horn & gets sent to
- Superior Cerebellar Peduncle (bundle of axons) - aids in motor movement
What kind of information does the Posterior spinocerebellar tract send & where does it send it to?
Information about tendons & muscle spindles & gets sent to
- Inferior Cerebellar Peduncle (aids in movement)
Differentiate Parietal and Visceral pain. Which is localizable?
Parietal - Parietal is localizable. Tissue pain; more tactile receptors.
Visceral - Deep organ interior. Not localizable. Less tactile receptors.
Would parietal or visceral pain have referred pain?
Visceral
What nervous system is visceral pain sent through?
Autonomic
What is pain threshold?
Ease or difficulty of giving someone pain
What happens after you’re in pain for a long time?
Upregulation of nociceptors, makes things more sensitive/painful. Also can impact emotions
What happens to the pain threshold in individuals that have a pain tolerance?
Threshold is raised
Where is the parietal pain from the appendix felt?
LRQ
In general, sharp/fast/localized pain will be ____ pain that is carried in ___ fibers
Parietal; A fibers
What kind of sensations are associated with visceral pain? What kind of fibers are they likely transmitted through?
Dull, achy, poorly localized
C-fibers
In regards to visceral referred pain, where would the kidneys hurt?
Back
What two organs don’t have visceral pain sensors?
Liver & lungs (wouldn’t feel pain after drinking or smoking for 30 years)
Can organs have both parietal and visceral pain? What organ is an example?
Yes; it can change the pain pathway depending on what is activated.
Appendix
Can appendix pain be relieved with lateral inhibition?
Yes
When releasing lateral inhibition pressure on the appendix, what happens?
Daddy says hurts like hell
Where is visceral appendix pain felt? Is it affected by lateral inhibition?
T10; cannot be suppressed
Where is referred pain from the heart? Why is this?
Left chest/left arm
Right side of the heart is not as prone to ischemia, left is though therefore referred pain to the left
(If pressures were equal on both sides, would have pain on both sides of chest)
Where is visceral referred pain of the stomach? What is it often confused with?
Maybe a heart worm per Schmidt, feel it little higher than umbilical
MI
“Ouch! My back hurts.” - patient
Where is this persons pain coming from?
Either kidneys or back injury
Where does the limbic system sit? What feeds into this?
Right on top of the brain stem
Slow pain; messes with your emotions and amplifies pain
Does fast pain mess with emotional state?
No
What are the three areas of the brain associated with the limbic system?
Amygdala, hypothalamus, cingulate gyrus
Where is the cingulate gyrus located? Is it still considered to be part of the cerebral cortex?
Deeper structure/gyrus located just outside the corpus collosum.
Yes
What does the cingulate gyrus do?
Processes some of the slow pain information
Where is fast pain processed?
Periphery of parietal lobe
What type of nerve fiber does the ANS use? Do we perceive this?
Type C; No
Which nerve fiber is considered to be well developed, more efficient, and faster? What neuron is it typically associated with?
Type A; motor
What type of nerve fiber does the muscle spindle feedback receptor use?
Type A; large
What type of nerve fiber do the muscle tendons use? What are they?
Type A; safety mechanism to make sure the tendon does not rip out of a bone
What type of nerve fiber do the various pressure sensors use around the body?
It varies depending on function
Where do pressure sensors get fed into? What fibers does this consist of?
DCML; variety of A-alpha, beta, gamma, delta
Generally, what kind of neurons make up the DCML pathway?
Large myelinated neurons (type A)
What kind of nerve fiber makes up the lateral inhibition fiber? Where does this ascend to the brain?
A-Beta fiber; DCML
What type of nerve fiber makes up the crude senses? i.e. ache, dull, nausea pain, cold, warm. Is this information “slow?”
Type C
While slower than type A, it’s still a fraction of a second because it is an action potential. It’s just slower than myelinated
Sharp/stab pains consist of what kind of nerve fiber? Can these be localized?
A-delta fibers
Yes
If you hit yourself in the hand with a hammer, what would be the order of sensations?
Pressure of hammer –> Very shortly after, sharp pain –> Shortly after that, dull achy pain that would mess with your emotions if it hurt for a long time
Do you have pain receptors on the cerebral cortex?
No
Do you have pain receptors on the dura? What happens with a CSF leak?
Yes; very sensitive. If you have a CSF leak it will lead to a terrible headache
What is the % of body mass attributed to skeletal muscle?
40%
What is the form of energy skeletal muscle stores?
Glycogen
What is glycogen?
Glucose molecules in a chain
what is a ligament?
Connective tissue that attachs one bone to another bone
What is a tendon?
Connective tissue that Attachs muscle to an insertion point on bone
What is an individual muscle cell also called?
Muscle fiber
What is a grouping of multiple skeletal muscle cells
Fasciculous
What is many Fasciculi?
Muscle
what is the cylinder found within the muscle fiber that contain actin & myosin called?
Myofibril
How many myofibrils can found in typical muscle fiber?
200 (up to the thousands in stronger muscle cells)
Muscle cells with fewer myofibrils can be used for what?
Fine motor movement
What is the contractile unit of the myofibril called?
Sarcomere
What occurs in the sarcomere?
Actin & myosin over lap (contraction)
What is a motor unit?
one of more muscle fibers controlled by a single motor neuron
Which motor neurons are easy to excite?
Small motor neurons
Which motor neurons are harder to excite?
Larger motor neurons
What is a type 1 skeletal muscle & what is the benefit of type 1?
Contains lots of mitochondria for ATP production & myoglobin
- it is darker in color (red)
- allows for slow contractions that have the ability to sustained
What is a type 2 skeletal muscle & what is the benefit of type 2?
Allow for quick movement, but can not be sustain
- fast twitch muscles
- do not contain a lot of mitochondria & myoglobin
- lighter in color (white)
What is myoglobin?
It is a large protein similar to hemoglobin, help unload oxygen from the blood to the skeletal muscle & has a higher affinity to O2 the Hgb
What produces the red color in myoglobin?
The iron
What is the soleus muscle? and what type of skeletal muscle is it?
Calf muscle & type 1
What type of skeletal muscle is the ocular muscle?
type 2 (fast twitch)
Where is the gastrocnemius located and how does this muscle differ?
Located next to the soleus muscle & is a combination of a fast contraction & sustained
what is the cell wall of the muscle cell called?
Sarcolemma
What is the fluid inside a cell called?
Sarcoplasm
What is the endoplasmic reticulum in a muscle cell called?
Sarcoplasmic reticulum
The alterations in colors in muscle cells are called?
Striations (found in cardiac & skeletal muscle)
What allows for deep penetration into muscle fibers?
Transverse Tubule (T-tubule)
The thicker filaments in the sarcomere are called?
Myosin
What are long strings of myosin molecules with tails wrapped around each other called?
Myosin filaments
The two ends of the sarcomere are called?
Z-disc
How many myosin molecules are in a myosin filament?
200 myosin molecules
The place where you would only find thick filaments is called?
H-Band (darker in color)
The place where you would only find thin filaments is called?
I-Band (lighter in color)
The place where you would find both thick & thin filaments is called?
A-Band
How many “chains” do myosin molecules have?
Six
what is the elastic connective tissue that fastens the sarcomere together?
Titin (large protein)
How many heavy chains make up the bulk of a myosin molecule?
Two
What shape do the two myosin heavy chains make?
Spiral
What does a heavy chain allow myosin molecules to do?
Fasten to other myosin molecules
What are the four additional chains at the head of a myosin molecule called?
Light chains
What are the two types of light chains? How many of each do we have?
Essential & Regulatory light chains
Two of each
Where is the essential light chain located? What does it do?
Furthest light chain on the periphery
Gives myosin head ATPase activity; essential for normal functioning of the myosin head
Where is the regulatory light chain located? What does it do?
The two proximal heads
Augments activity of a muscle
The overall contraction of the myofibril is referred to as?
Sliding Filament Mechanism
Do regulatory light chains have much effect on skeletal muscle? What about smooth muscle?
They do not do much for skeletal muscle; regulatory light chains are useful in muscle that requires phosphorylation of myosin heads.
Smooth muscle has phosphorylation of myosin heads, and has more use for regulatory light chains.
Takeaway point: Smooth muscle regulatory light chains are important
What kind of contraction would warrant the use of a regulatory light chain?
A very fast/strong contraction
What do myosin heads have an affinity for?
Binding sites on the actin filament
What is the other name for the binding site on actin?
The active site
What is special about the myosin head?
Has ATPase activity; can burn ATP and has an active site for binding.
What happens over all in the Sliding Filament Mechanism?
Actin gets pulled towards myosin, z discs get closer together & I bands disappear but myosin doesnt move as it has a fix position
The striations of actin filaments can be thought of as alternating strands. What are the names of the two strands?
F-Actin
Tropomyosin
Describe the differences in protein production and transport system in a motor neuron vs skeletal muscle
Motor Neuron - takes proteins produced and essentially transports them down axon using cart and tracks
Skeletal muscle - multi-nucleated, no transport system
What is the function of F-Actin?
Has binding sites for myosin heads
What is the function of tropomyosin?
Functions as a shield.
i.e. if a muscle is not contracting, tropomyosin is oriented in a way where the myosin head can’t see the binding sites of actin. It just blocks it.
What has to happen to tropomyosin to get skeletal muscle contraction?
It has to be moved out of the way of actin/myosin head.
What moves tropomyosin out of the way to allow for the myosin head to bind to actin?
Troponin complex
What is the troponin complex?
3 proteins stuck to one another.
Troponin-I
Troponin-T
Troponin-C
Where is Troponin-I bound?
To the actin strand
Where is Troponin-T bound to?
To tropomyosin
Where is Troponin-C bound?
Troponin-I & Troponin-T
What process does the troponin complex undergo to remove tropomyosin?
Troponin-C has 4 binding sites for Ca++. When Ca++ binds to Troponin C, it twists the other two proteins (Myosin/tropomyosin).
This twisting moves tropomyosin out of the way, unravels the strands just a bit, and allows for binding of the myosin head to actin.
Troponin-C can alter how strong muscle contraction will be.
What are the steps of cross-bridge cycling in skeletal muscle?
1) Calcium binds to Troponin C
2) Tropomyosin unblocks myosin binding site
3) Myosin head binds to active site on actin
4) Phosphate leaves myosin head, stored tension from P pulls on actin molecule, thus pulling ends of sarcomere closer to one another
5) Head is now bent, it has “walked actin backwards” to produce force.
6) To release the myosin head, ATP use used, ADP is remaining
In the cocked state, what position does the myosin head have in relation to actin? What is attached to the myosin head?
Perpendicular; P & ADP
In the released state, what is the shape of the myosin head and what is attached to it?
Bent; ATP
What is attached to the myosin head in the weak cross bridge state? Is myosin attached to actin?
P & ADP
Yes
What is attached to the myosin head in the strong cross bridge state? Is it attached to actin?
ADP; yes
What is attached to the myosin head in the post power stroke state? What is happening here?
ADP; contraction. Myosin pulls on actin, pulling the sarcomeres closer to one another.
What is bound to the myosin head in the attached state?
Nothing
What is attached to the myosin head in the released state?
ATP
If you are out of ATP, can you reset myosin heads?
No
If you’re out of ATP and can’t release the myosin head from actin, will there be sustained contraction?
No, only tension
What is the pathophysiology of rigor mortis?
Deficiency in ATP, leading to myosin heads being stuck to actin. This results in stiffness.
The majority of motor neurons innervate how many muscle cells?
More than one
In a microscopic image of a muscle, the purple dots represent _____
NMJ
Order of excitation-contraction coupling?
Initial electrical event -> Force
End plate potential –> AP –> Liberation of Ca though DHP/ryanodine receptors –> Bind to troponin-C –> Myosin head binds to actin –> Myosin head pulls on actin to bring sarcomeres closer to one another, producing force
What are the two things that determine strength of contraction?
-Surface area involved
-Interaction between thin and thick filaments (actin/myosin)
A sarcomere is stretched to the extent that actin and myosin do not cross bridge Does this happen in the body?
No; also no
A sarcomere is not stretched fully, whereas another is stretched a little more. Myosin and actin are overlapping in both scenarios. Which one is stronger?
The slightly more stretched one
What other part of an important organ is similar to the skeletal muscle sarcomere? How does it apply?
Left ventricle; as heart walls get thinner and more stretched over time due to overstress, force of contraction reduces.
The less you over stress a muscle, does force increase or decrease?
Increase
Why would a non-optimally stretched muscle not have as much force as an optimally stretched one?
Less room for the sarcomeres to stretch when pulled
Normal placement of _____ gives good tension/optimal stretch to skeletal muscle.
Tendons
If you have more bulky muscle, or are playing football etc., what should you do?
Stretch to make sure you are optimally stretched for better performance
What does the achilles tendon fasten?
Fastens the gastric and soleus muscle to the calcaneous heel bone
If we rip the achilles tendon and fix it surgically, what normally happens?
The muscle is slightly more stretched because they stitch the ends together so it’s not quite as long anymore. In normal people this usually isn’t a big deal, but in athletes it can be a major change.
How can we avoid elite athletes being bothered my achilles tendon repairs?
Having their coach spend lots of $$$ to get a cadaver tendon and hire an expensive skilled surgeon
How does the heart relate to the sarcomere? What law does this demonstrate?
Increased filling pressure/venous return = greater contraction to pump out additional blood. Pumping is augmented by the sarcomeres of the heart. Normally, they are under stretched to accommodate for extra stretch.
This is known as the frank starling law. Greater stretch = greater contraction/pumping (within reason)
What name describes increased stretch = increased contraction other than frank starlings?
Length-tension relationship
What is the force called to achieve stretch?
Passive tension
What is the name of the force that’s produced in the contracting muscle as a result of an action potential?
Active tension
Do prostaglandins cause pain? If not, what do they do?
No, not by themselves. They can augment pain and make it worse.
Why does ischemia cause pain?
Build up of metabolic waste (lactic acid can’t get cleared because perfusion is bad)
How do you elicit the stretch reflex? What happens?
Whacking someone with a mallet on the ligament right below the patella.
Leg kicks forward (antagonistic muscle [hamstring] relaxes, quads contract)
What is the pathway/order of the stretch reflex? Start with stimulus, end with leg kicking out.
1) Stimulus –> Muscle spindle receptor senses stretch
2) Sensory neuron sends AP to through afferent (rear) of cord
3) Within integrating center (spinal cord) sensory neuron activates the motor neuron.
4) Efferent signal sent to quad resulting in contraction, while interneuron sends signal to relax hamstring
What is the goal of the stretch reflex?
To keep muscles a constant length.
What kind of sensor does the stretch reflex use?
Muscle spindle
What kind of body part is the stretch reflex applicable in?
Weight bearing portions of the body, such as the legs
What is the purpose of having the stretch reflex engaged while standing?
To keep constant posture
If you pushed on someones forehead and they continue to stand after adjusting themselves, what is this from?
Stretch reflex
If you pushed someone on the forehead who lacked the stretch reflex, what would happen?
They would fall
Does the stretch reflex require an interneuron to elicit a response?
No, one AP from the stretch sensor can reach to the motor neuron
Why does the stretch reflex use an inhibitory interneuron?
Hamstring relaxation (looser than baseline tone)
Does the stretch reflex stay on one side of the cord?
Yes
In the stretch reflex, what is the quad considered?
The extensor muscle
What is the hamstring considered in the stretch reflex?
Antagonist muscle
What is the primary goal of the tendon reflex?
To prevent our tendons from pulling out of our bones
What kind of sensor is involved with the tendon reflex?
Golgi tendon sensors
What two things happen during the tendon reflex?
-Cease contraction under heavy load to prevent tendon tears.
-Contract antagonistic muscles to speed retraction from load source.
If someone fell out of a tree, would they break bones? How about muscles? Why?
Bones are likely to break.
Given the massive pressure/strain on muscles, the tendon reflex would be activated, leading to decreased tension on the muscles carrying load. Muscles would not be torn from insertion points.
How can we get around the tendon reflex? (i.e., lifting a car off a child)
Daddy Schmidt says he doesn’t know
What does the inhibitory interneuron do in the tendon reflex?
Inhibits motor neuron of extensor muscle (quad)
What does the excitatory interneuron do in the tendon reflex?
Reflex activation of antagonistic muscle (hamstring)
How many interneurons does the tendon reflex use?
Two
Other than the legs, where is the tendon reflex also found as mentioned in the powerpoint?
Biceps/triceps
How many sides of the cord does the tendon reflex involve?
One
What is another name for the flexor reflex?
Withdrawal reflex
What kind of general receptor does the flexor reflex involve? Given this, what is the goal of this reflex?
Pain receptors; pull away from pain
Is the flexor reflex on one or both sides of the cord?
One
What kind of muscle sets are activated with the flexor reflex? Why?
Flexor muscle sets. Pulls body part away from what is causing the pain
Sometimes in the flexor reflex, the antagonist muscle set would activate. Why would this happen, and which muscle is which?
Pull away from pain faster.
Flexor - hamstring would contract
Antagonist - quad would relax
Typically, if a reflex is more urgent, it will activate ____ muscle.
More/larger
In the cord, what is special about the flexor reflex?
It works a few levels below and above the site of stimulus.
Specifically in class, “two levels above and two levels below the stimulus.”
What is the interneuron responsible for transmitting pain signal up/down the cord in the flexor reflex called?
Tract of Lissaur
Where is the Tract of Lissaur located? What kind of matter is the cell body located in?
Just posterior to the dorsal border of the dorsal gray horn.
White matter
What would happen to reflex pathways in a patient with a spinal block? What else can do this?
They may be inhibited with a deep block. Sedation can do this as well.
What does a deep block imply in regard to pain?
Not a guarantee that pain will be blocked, but if reflexes are blocked it’s a decent rule of thumb that pain will be blocked.
What is the pathway from stimulus to action of the tendon reflex?
1) Increased tension of muscle (quad) picked up by Golgi tendon sensors
2) afferent pathway activated to cord
3) Sensory neuron activates inhibitory interneuron within cord
4) Motor neuron inhibited (quad)
4a) Excitatory neuron contracts antagonistic muscle (hamstring)
5) Effector muscle (quad) relaxes and relieves excess tension
5a) antagonistic muscles also contract via excitatory interneuron
What is the pathway from stimulus to action of the Flexor reflex
1) Kick a nail/door/etc
2) Sensory neuron excited, enters cord via afferent pathway
3) Within integrating center (cord), sensory neuron activates interneurons 2 levels above, 2 levels below signal (through tract of lissaur)
4) Motor neurons excited, exit efferent pathways of cord
5) effector muscle (flexor muscles) contract and withdraw leg
What is the difference between the flexor reflex and the crossed extensor reflex?
The crossed extensor reflex is on both sides of the cord, and happens mid-stride.
What is the order of the four reflexed talked about in class, simple to complicated?
Stretch –> Tendon –> Flexor –> Crossed extensor reflex
What does the crossed extensor reflex do if you are walking and stub your right foot?
Your right foot withdraws while your left leg extends to get a solid base to stand on/push away from the painful stimulus
The crossed extensor reflex involves multiple levels on both sides of the cord. These levels are activated by the _____
Tract of lissaur
Does the crossed extensor reflex use interneurons other than those in the tract of lissaur?
Yes; interneurons help the AP reach the other side of the cord.
Can we have the crossed extensor reflex in our arms?
Yes
What is the pathway from stimulus to response of the crossed extensor reflex?
1) Kicking a painful object stimulates dendrites of pain sensitive neuron in right foot
2) afferent neuron excited, sends AP to cord
3) Within integrating center (cord), sensory neuron activates several interneurons.
3a) Tract of lissaur
3b) Interneuron to cross to other side of cord
4) Motor neurons excited, AP sent through efferent pathway
5) Flexor muscles contract and withdraw right leg (quad)
5a) Inhibitory interneuron relax right antagonistic muscle group
5b) Extensor muscles contract and extend left leg to push away from the stimulus and get a solid base to stand on
5c) Inhibitory interneuron relaxes antagonistic muscle group in left leg
What is the other name for the other side of the cord?
Contralateral cord
Where are nACh-R normally located?
At the NMJ
What type of nACh-R is at the NMJ in a healthy adult?
High-Conductance channel (mature)
What type of channel is a nACh-R?
Ionotropic
How many domains are on a high conductance channel (mature)?
Considering a clock, where is each domain located?
Which domains do ACh bind to?
5 domains
11 - Alpha 1
2 - Beta 1
4 - delta (g)
6 - alpha
8 - Epsilon (reverse 3; looks like E)
ACh binds to alpha 1/alpha
What is the unique characteristic of a high-conductance channel (Mature)?
Ion channel stays open for a very short period of time
What kind of nACh-R does an infant have?
Low-conductance channel (immature) (fetal)
What domains does the low-conductance channel (immature) have? Where are they in relation a clocks hands?
5 total
11 - alpha 1
2 - beta 1
4 - delta (g)
6 - alpha
8 - gamma (y)
What is the difference between the domains of a mature and immature nACh-R?
The epsilon domain of the mature nACh-R swaps for a gamma domain in the immature version.
What age group is the low conductance channel normally found?
Newborns/very young people
Are low conductance channel only found at the NMJ?
No; they are at the NMJ and also along the entire skeletal muscle.
Is ion conductance in Low conductance channels higher or lower than in a healthy adult?
Lower; it’s in the name. Potentially because the channel doesn’t open as wide, making it functionally different.
What is the major difference between the low conductance channel and the high conductance channel?
The low conductance channel stays open for a longer period of time than the high conductance channel.
Where are alpha 7 ACh-R found? What domains are present? Which ones bind to ACh?
Found within the CNS
5 alpha-7 domains; all bind to ACh
note: this is all we need to know about these for our class
Does Sux have a greater effect on low or high conductance channels? Why?
Low conductance - long period of time that the channel is open compared to the high conductance version.
What happens to the skeletal muscle in patients with motor conditions?
It becomes studded with Low-Conductance channels along the length of the muscle outside the NMJ.
The brain looks for sensor feedback during contraction. If someone has a motor condition and the muscle doesn’t contract, how does the CNS/body respond?
Body tries to fix it by expressing lots of low conductance channels all over the muscle
When the body populates the skeletal muscle with low conductance channels, what disease state can be helped? Why?
Myasthenia Gravis
Lack of nACh-R due to antibodies. Having more nACh-R = more nACh-R activity leading to increased strength
From day to day, do the extra low conductance channels all over the skeletal muscle really matter?
No; outside the NMJ and ACh has a very short half life + Acetylcholinesterase.
What drug is contraindicated in patients with motor problems/CVA? Why?
Sux
Low conductance channels stay open for a long period of time at baseline. If Sux is given, the channels stay open for significantly longer. The sux will also activate all of the low conductance channels studding the muscle, leading to massive amounts of K outflow.
This puts the patient at risk of v-fib
Are L-type Ca channels required for action potentials?
No, they are just supplementary. They are not required for an action potential.
Does the L type Ca channel open fast or slow?
Slow
Can you paralyze someone with a calcium channel blocker that works on the L-Type channels?
No
If you were out partying all night and are shaky and drunk from ethanol, what can help them not be so shaky?
Calcium channel blocker will settle them down
Does every muscle respond to paralytics in the same way?
No; smaller muscles take less paralytic to paralyze than a larger muscle
What is the adductor pollicis muscle used for? Will you immediately die if you paralyze this muscle
Important for working with hands, writing, fine motor control
No
Is the adductor pollicis more or less sensitive to paralytics than the diaphragm?
More
Would a more important muscle such as the diaphragm have more NMJ than a less important muscle? What would this mean in terms of inducing paralysis?
The diaphragm (or other more important muscles) have robust NMJ systems.
The more NMJ on a muscle, more paralytic will be required to paralyze it.
What two cavities does the diaphragm separate? What kind of muscle is it? Why is this important?
Abdominal and thoracic cavities
Skeletal muscle; can be paralyzed since it’s a skeletal muscle
What is the diaphragm innervated by?
The phrenic nerve
Where is the phrenic nerve located?
C3-C5
If you take a spear to T2, will you have trouble breathing assuming the spear misses all airway/CV components?
Aside from pain, no. Diaphragm is innervated by the phrenic nerve which is located at C3-C5
If you have a lesion on C4, what would happen?
Partial or complete block of diaphragmatic outflow - need to ventilate
When stopping paralytics, what muscle would come back online between the diaphragm or the adductor pollicis?
Diaphragm - larger muscle, more NMJ
What is a good rule of thumb, but not a guarantee that the patient will have diaphragmatic tone when reversing paralysis?
4 twitches on TOF in the adductor pollicis should indicate diaphragmatic tone, but not guaranteed.
In regard to % of nACh-R blocked when testing TOF, when does the 4th twitch disappear?
75-80% blocked
In regard to % of nACh-R blocked when testing TOF, when does the 3rd twitch disappear?
85% blocked
In regard to % of nACh-R blocked when testing TOF, when does the 2nd twitch disappear?
85-90% blocked
In regard to % of nACh-R blocked when testing TOF, when do all twitches disappear?
90-95% blocked
In regard to % of nACh-R blocked when testing TOF, when is head-lift in a reasonably healthy patient blocked?
70% blocked
For the purpose of our class (dependent on clinical site really), what is the nerve stimulator set to? What is this referred to as?
50-80mA (supramaximal stimuli)
This is referred to as current
If someone can lift their head, what does this mean?
Patient likely will have all 4 twitches present as rule of thumb, not a guarantee though
What is the “push of electrons” referred to in terms of batteries?
Voltage (force battery can use to apply current)
What are the two parts of an electrode?
Cathode
Anode
The ocular muscles are controlled by ____ motor neurons
Several
If you give sux to a patient, does Ca come in to the muscle? Is there contraction of the muscle? If so, where?
Yes
In ocular muscles, yes but not in normal large muscles other than the initial depolarization
In patients with motor issues and you give sux, aside from K leak, what would happen?
Ca would enter through fetal receptors, could contract the muscle
What is a side effect of sux to consider other than K leak?
Increased ocular pressure due to small contractions of ocular muscles from Ca entering the muscle
Can lead to pressure/stress on the optic nerve with loss of vision if it is for an extended period.
What is the main inhibitory CNS neurotransmitter? How does it do it?
GABA; mediates inhibition by increasing Cl- conductance/permeability. This suppresses the nervous system.
What is the main inhibitory neurotransmitter within the spinal cord? What else does it use?
Glycine is the main inhibitory neurotransmitter of the cord.
It also uses GABA
Don’t need to know MOA glycine, just know it works like GABA and is important to the cord
“If I ask on the test what the two most important inhibitory neurotransmitters are, it is ____ ____”
GABA & Glycine
What does Acetylcholine do in the CNS?
Increases awareness. The more we have, the more aware we are
Why would you use an acetylcholinesterase inhibitor that doesn’t cross the BBB?
If you don’t want to wake them/make them more aware
What do you prescribe someone with Alzheimers, and why?
-Stigmines
Crosses BBB; more nACh-R activity in the brain to make them more present
Side effect of -stigmines
Waking people up; augments ACh activity anywhere where there is ACh
What is another way to get Active tension from total tension?
Total tension - passive tension = Active tension
In the example with a weight & a muscle, how was the passive tension determined?
The passive tension was the tension measured when a muscle was attached to a tendon stretching the muscle
In the example with a weight & a muscle, how was the Total tension determined?
The total tension was measured when the muscle contracted with the weight attached due to an action potential
In the example with a weight & a muscle, how was the Active tension determined?
The active tension was determined by subtracting the passive tension from the total tension
In the Load/contraction diagram, a higher load equates to?
A lower velocity (the muscle will take longer to contract)
In the Load/contraction diagram, a lighter load equates to?
A higher velocity (muscle will contract quicker)
The load/contraction diagram is important in which organ & why?
The Heart
- the higher the afterload, the longer it takes the heart to eject the blood
The recruitment of more motor units is referred to as?
Quantal Summation (quantity)
What is quantal summation managed by?
Voltage
- the higher the voltage the more motor units recruitment
What is Temporal summation?
strength of contraction related to amount of Hertz (stimulation per second)
What will we see at <10 Hertz being applied to muscle?
Individual contractions, with ability to fully relax after each contraction
What will we see at 10-12 Hertz being applied to muscle?
Contractions become additive, no complete relaxation before next contraction
Why do the contraction become additive at 10-12 Hertz?
Calcium is coming out of the SR faster than it can be put back in the SR before next AP –> leads to more calcium being in the cell –> leads to stronger contractions
What will we see at greater than 40 Hertz being applied to a muscle?
Tetanization
- caused by there being so much calcium being in the cell, the twitches seen are lost, this occurs when the cell is hit with so many rapid APs the calcium receptors in the muscle are close to saturation
How about how much more force can Temporal generate vs Quantal summation?
about 3 times as much
Fast enough temporal summation can lead to?
Tetany
The lack of muscle use can lead to?
Atrophy
In the case of Atrophy what begins to disappear first? and what follows it if atrophy continues?
Myofibrils disappear first followed by muscle fibers
Exercising can lead to ___; which is an increase in ___
Hypertrophy; Myofibrils (vasculature will also increase & become large)
Excessive exercise can lead to __; to which after a LONG time can generate more ___
Hyperplasia; Muscle Fibers
What is an example of Hyperplasia discussed in lecture?
The Heart - it can generate new muscle fibers but it takes a LONG time, it cannot repair serious damage such as MI
What is downside of being able to increase Hyperplasia in the muscles through a medication?
Anything that increases cell division can also increase the risk of cancer development
What is the body mass % smooth muscle takes up?
10%
Why is smooth muscle more efficient vs skeletal muscle?
Cross bridge-cycling occurs at a much slower pace
- it take longer for the myosin heads to release from actin which conserves the the tension that was created in the muscle.
On a gram to gram ratio, which is stronger skeletal muscle or smooth muscle?
Smooth muscle
What is the Ultra low state refer to in the smooth muscle?
“Latch” Mechanism
- Very slow cross bridge cycling to the point where myosin heads have difficulty releasing from actin –> can maintain force of contraction for a long period of time with very little energy use
What is the ratio for actin & myosin skeletal muscle vs that of smooth muscle?
Skeletal muscle:
- 2 to 1 : actin to myosin
Smooth muscle:
- 10-20 to 1 : actin to myosin
What is the Dense body?
Spherical structure where actin is anchored & links to neighboring smooth muscle cells
How does the SR in the smooth muscle differ from that of the Skeletal muscle?
The SR in the smooth muscle is not well developed, muscle contraction in smooth muscle is more dependent on outside calcium coming in vs. SR
What are some ways calcium can come into smooth muscle?
- leaky channels (it has a lot)
- V-G channels
- Ligand gated channels
If a pt were to come in with a blood calcium level of 0, how would this affect the heart & BP?
Heart - would have no calcium to induce calcium release (outside calcium is what triggers SR to release stored Ca) –> no contraction
Smooth muscle - is dependent on outside calcium for contraction –> no Ca would lead to no smooth muscle contraction or no tone
What the two types of smooth muscle? & what is the vast majority of the body composed of?
Visceral (unitary) & Multi-unit
- vast majority is Visceral
What are some characteristics of Visceral smooth muscle?
- also called “unitary”
- communicates through Gap Junctions
- contract as a unit
- Most of the lining of our hollow organs are visceral
What are some characteristics of Multi-unit smooth muscle?
- no gap junctions
- communicate through neurotransmitters
- neurotransmitter dependency allows for fine tune movement
- Eye muscles are an example of multi-unit smooth muscle
Which organ is a hybrid of both Visceral & Multi-unit smooth muscle?
Esophagus
What are the three layers of Blood vessels & their alternative names?
Endothelium - Tunica intima (innermost)
Smooth muscle - Tunica media (middle)
Adventitia - connective tissue - Tunica Adventitia (outermost - structural support)
Which two layers blood vessels communicate with each other & how do they do it?
Endothelium & smooth muscle
- communicate through neurotransmitters or gases
Which is the only blood vessel that doesnt contain smooth muscle?
Capillary - exclusively made up of endothelium
What are some differentiating characteristics between Skeletal muscle sarcomere & smooth muscle sarcomere?
Skeletal muscle sarcomere:
- m-line: creates gap in myosin where there is nothing & differentiates left from right on sarcomere
- all myosin heads are oriented at an angle spreading out from the middle
Smooth muscle sarcomere:
- no m line
- myosin on opposite ends face the opposite way
- able to shorten smooth muscle more than skeletal muscle
Which ACh receptor makes us drowsy/puts us to sleep?
mACh-R
What class of drug is an antihistamine that cross reacts with mACh-R? What is the result?
Given that it is an old drug that isn’t very selective, what else might we see?
Benadryl that works in CNS; sedation
Also can see spike in HR due to blocking mACh-R in heart
What works in the CNS similarly to ACh?
Histamine; more histamine = more wakefulness
What neurotransmitter has a pain transmission role? Is it stimulatory or inhibitory? What does it do to neuronal activity?
Glutamate; stimulatory; increases neuronal activity when in high levels
People who are high on meth have what a high level of ____
Glutamate; stimulatory, very awake and sense of being alive
Over time; being high on meth does what to the brain? Why?
Brain cells get “burnt out.” They do not return once they are gone. This happens if glutamate is very high for long periods of time.
Which neurotransmitter is the “happy” neurotransmitter?
Dopamine
Other than being a happy hormone, what else does dopamine do?
Motor inhibition
If we have a lack of dopamine, it leads to _______ disease
Parkinsons. Overactive motor system
What neurotransmitter increases awareness in CNS other than histamine?
Norepinephrine
What kind of drug used by patients with depression help with norepinephrine levels? Can this help with chronic pain?
SNRIs; yes
What affects CNS activity as described in class outside of neurotransmitters/glucose?
Acid base balance
If a patient is acidotic, CNS activity is ____
Reduced
If a patient is basic, CNS activity is _______
Increased
How does acid-base impact CNS activity?
it affects Calcium levels
What does the body use to buffer acids in the blood?
Bicarb (HCO3)
When bicarb combines with acid, ____ is formed which can dissociate into ____ and ____
Carbonic Acid
CO2; Water
Typically, in the blood we have significant amounts of plasma proteins such as ______
Albumin
Albumin is _____ charged
Negatively
What can buffer acid (H+)?
Negative charges, such as those on albumin
What ion likes to hang out near albumin?
Calcium
____ _____ is dependent on how many H+ ions we have
free calcium
If we have a lot of protons hanging around, albumin will be covered with H+ and we will have ___ free calcium
More
An increase in free Ca/low pH _____ CNS activity
Reduces
A decrease in free Ca/High pH _____ CNS activity
Increases
If we had a high pH, there would be ____ room on albumin for calcium. This would result in free calcium being ____. CNS activity would be ______
More
Low
Increased
In a patient who hyperventilated, would there be more or less room for calcium on albumin? If hyperventilation continued, it would eventually lead to ____. Why?
More
Seizures
CNS activity is increased with lack of free calcium
A patient who hypoventilated would have ____ room on albumin for calcium. This would result in ____ free calcium, _____ CNS activity.
less
More
Inhibiting
With a low pH, ____ combine with ____ to form ____ ______, leading to the byproduct of ___ and ____
Bicarb & H+
Carbonic acid
Co2 & water
What are the seven things mentioned in class that can cause pain?
- Damage
-Acid (lactic acid –> increased K with acidosis, depolarizes cell and leads to pain)
-Histamine (inflammation)
-Serotonin (inhibitory in cord, painful in periphery)
-ACh in periphery
-Prostaglandin (inflammation)
-Bradykinin (produces prostaglandins)
Does the descending pain suppression system get rid of pain completely?
No; takes the edge off though. It operates in the backdrop to help the body deal with pain.
When is the descending pain suppression system activated?
In response to pain once pain reaches the brainstem
Drug that reuptakes serotonin inhibit pain how?
Serotonin is inhibitory in the cord, leading to decreased pain.
What two SSRIs were mentioned in class regarding treating chronic pain at the level of the cord?
Paxil
Prozac
Using a SSRI works where in the descending inhibitory complex?
3rd order inhibitory neuron
Why are SSRIs used over tricyclic antidepressants for chronic pain?
SSRI are more specific
What neuron runs right next to the nociceptor neuron?
DCML neurons
Putting pressure on an area that hurts makes it feel better. This is known as ______ _______
Lateral inhibition
How does lateral inhibition work?
Unknown, but thought to be through neurotransmitters that can shut down their neighbor
Is enkephalin excitatory or inhibitory?
Both; excites the nucleus raphe Magnus, releases serotonin (5-HT)
Inhibits enkephalin receptors on nociceptor & ascending pain pathway
Where is 5-HT (serotonin) released?
In the cord around the dorsal horn
What does serotonin work on in the DIC? Where is it located?
Enkephalin secreting neuron (3rd order)
Enkephalin binds where once released?
Dendrites on nociceptors in the periphery
What is another name for the endorphin/enkephalin system?
Endogenous opiate system
Where is the enkephalin neuron within the lamina? Where does it go from there?
Between laminate 1,2,3 depending on the type of pain. Transmission hops over via anterior white commissure and ascends in the anterolateral pathway
Are enkephalin receptors on the nociceptor or ascending pain pathway, Excitatory or inhibitory?
Both; Inhibitory
Enkephalin is considered an analog to which drug?
Morphine
All _____ receptors are enkephalin receptors.
Opiate
The first synapse within the DIC is in the middle of the ____. It is known as ____ _____ ____
Pons
Raphe Nucleus Magnus
If we generated an impulse via electrodes in the periventricular nucleus, what would happen? What is this called?
An inhibitory pain signal would be sent.
Deep brain stimulation
An exogenous drug class that works well within the DIC pathway are _____.
opiates
Does DIC affect slow or fast pain?
Both
Why doesn’t DIC work in reverse adaptation of the nociceptors?
With chronic pain, there are more neurotransmitter receptors available.
Glutamate is unregulated and is difficult to inhibit.
Increase in glutamate receptors.
If prostaglandins are inhibited, would there be less pain?
Yes
Where does serotonin augment the DIC?
3rd order inhibitory neuron
_______ is based on lateral inhibition at the dorsal horn.
Acupuncture
______ is always excitatory, and is the top neurotransmitter for pain - especially fast pain.
Glutamate
(slow pain)
first order pain receptor synapses at lamina _, _, and _. It crosses via the ____ ____ ____, ascends the cord within the _____ ___ ____ to the brain. Most of the pain terminates in the ____, but some makes it to the ____. Is this pathway myelinated?
2, 3, 5
Anterior white commissure
Anterior spinothalamic tract
reticular formation
Thalamus
No
What type of pain involves emotional centers of the CNS and messes with our heads? What neurotransmitters are involved? Which is faster?
Substance P, CGRP (slower)
Sometimes glutamate (much faster)
Fast pain travels along a ________ nociceptor fiber. In comes through the back of the cord, synapses at lamina ___, crosses via the ____ ____ ____, ascends via the ____ _____, passes through the _____, and nearly all of the pain signal is sorted within the ____ ____. The neurotransmitter for fast pain is ____.
Myelinated A delta
Lamina 1
Anterior white commissure
lateral spinothalamic
Thalamus
Parietal lobe
Glutamate; fast to be released/bound
Do the DCML and pain pathways meet?
Yes
Are 2nd order neurons myelinated?
Most are, but not all of them. Difference is mostly seen on first order neurons/nociceptors.
Ascending tracts are almost always myelinated for fast pain, and sometimes for slow pain.
DCML and nociceptor pathways are ____
Parallel
DCML sensory information can go up pathways of the cord or ____
Stay at that level of the cord
What channels are on the 2nd order neuron? All of these channels are ___ ____ receptors. They increase cell permeability to ions when bound with _____.
AMPA-R
NMDA-R
Kanate receptor
Ionotropic glutamate receptors
Glutamate
AMPA-R binds with ____ released from the 1st order neuron. When bound, the AMPA-R lets ____ into the 2nd order neuron which then sends an action potential to the brain.
Glutamate
Sodium
NMDA-R binds with ___ to allow ___ into the 2nd order neuron.
Glutamate
Calcium
Which is faster to generate current - NMDA or AMPA?
AMPA - sodium is faster, calcium is big and clunky
_____ blocks the inside of the NDMA-R at rest.
Magnesium ion
When AMPA-R is open, it makes the 2nd order neuron more _____ which pushes _____ away from the NDMA-R, allowing ____ to enter.
Positive
Magnesium
Calcium
NMDA-R is a ___ ____ calcium channel.
Voltage gate. It is not a P-Type.
____ is required for the 1st order neuron (nociceptor) to release glutamate from vesicles.
Calcium; it comes in via calcium ion channels on the nociceptor.
What can block NDMA? (list 5)
-Ethanol (CNS inhibitory)
-Lead poisoning (old paint, extra bad around children; affects development of nervous system, specifically NDMA-R. Don’t let your kids eat pain off the wall please..)
-Ketamine (dissociative, inhibits NMDA-R; takes Ca++ away so we don’t feel as much pain)
-Nitrous (Makes pain more tolerable)
-Tramadol (Has an SSRI effect + inhibits NDMA)
What receptor do we not have many of when we’re born, but get more over time as we develop? (2nd order neuron)
NDMA-R
If the NMDA-R is shut down, is it enough to shut pain off?
No, AMPA still firing but pain perception is reduced
What drug sucks and shouldn’t be used post-op?
Tramadol, daddy says it’s terrible
What drug can be used in opiate sensitive elderly people for pain?
Tramadol
While we have three ionotropic glutamate receptors (AMPA, NMDA, kanate), we also have __________ found more in the ______.
Metabotropic receptors
Brain
Are metabotropic receptors inhibitory or excitatory?
Excitatory
Are ionotropic receptors faster than metabotropic receptors?
Yes
What causes the calcium channel on a nociceptor to open? (1st order neuron)
Action potential
Other than glutamate, what else can bind to AMPA/NMDA receptors? What is another name for these receptors?
Enkephalins
Mu/Opioid receptors
How do opioid receptors work?
Opens K channels, making the Vrm more negative.
What drug class will shut down the 2nd order neuron? How does it do it?
Can you get addicted to this drug class?
Alpha 2 agonists
Increases K permeability
No
Which three alpha 2 agonists were listed in class? Which is more specific?
Xylazine, clonidine, and dexmetetomidine
Dexmetetomidine is more specific
Of the three alpha 2 agonists mentioned in class, which one is a tranquilizer and has the potential for abuse?
Xylazine
What drug class always suppresses the CNS when used with a vaporizer?
How?
Volatile anesthetics
Opens K channels throughout the CNS, making Vrm more negative.
Other than NMDA/AMPA receptors, what else is induced with pain on 1st and 2nd order pain neurons?
COX2
COX2 produces ______
Prostaglandins
When prostaglandins bind to prostaglandin receptors located on the 1st/2nd order ascending pain transmission neurons, it _______ pain and increases likelihood of _____ action potentials.
Increases
Multiple
When prostaglandin is bound to prostaglandin receptors, will it cause an action potential alone?
No; prostaglandin only modulates pain
Does all smooth muscle work the same?
No; it depends on the area of the body.
When the vascular bed smooth muscle is stimulated to ACh, what happens?
Relaxation
When the intestinal smooth muscle is exposed to ACh, what happens?
Contraction
Which is more developed - SR in smooth or skeletal muscle?
Skeletal muscle
Do tropomyosin block actin/myosin heads from each other in smooth muscle?
No; it is there, just doesn’t really do anything
Where does regulation of contraction occur in smooth muscle?
Regulatory light chain of the myosin head (heavy chains/myosin filaments)
What is required of the myosin head in smooth muscle to cycle ATP?
Phosphorylation of the myosin head
What primarily determines activity of the smooth muscle? What does it do?
Kinase; Sticks phosphate on “stuff.”
Because it puts phosphate on the regulatory light chain of the myosin head, the kinase in smooth muscle is called the ______
Myosin like chain kinase (MLCK)
When MLCK is very active, we will have a lot of ______ myosin heads
Phosphorylated
What determines MLCK activity?
Calcium availability (more = more activity)
Once calcium enters the cell through a Ca channel, what does it bind to? What does it form?
Calmodulin
Ca++ calmodulin complex
What does Ca++ Calmodulin complex do in the cell?
Wraps around inactive MLCK and twists it to activate it
Where does Ca come from in smooth muscle? Why?
Most come from outside of the cell.
The SR within most smooth muscle is immature and doesn’t store much Ca.
What are the ways that Ca can enter smooth muscle cells?
Ca++ leak channels
L-Type Ca channels (Slow to open, stay open for a long time — this is one of the main methods)
Ligand gated ion channels
Lesser amount from immature SR
Once MLCK is active, what happens?
The myosin head pulls on actin, bringing sarcomeres closer, leading to muscle contraction
What does smooth muscle relaxation depend on?
Dephosphorylation of the myosin head
Will phosphates remove themselves from myosin heads of smooth muscle? What can speed this process up?
Yes
The enzyme myosin phosphatase strips the myosin head of phosphate, thus inactivating it
Other than stripping the phosphate off of the myosin head, what is another way to relax smooth muscle? What are some ways to do this?
Removing calcium
SERCA pump, Plasma membrane calcium ATPase pumps (PMCA), and the Na/Ca exchanger (3Na in, 1 Ca out)
How does the plasma membrane ATPase pump work? (PMCA)
One calcium out, one ATP used; same as in skeletal muscle
After calcium leaves the cell via the Na/Ca exchanger, what “cleans up” the Na remaining in the cell?
PMCA (plasma membrane calcium ATPase) used towards the end of calcium removal
Na/K/Ase cleans up leftover Na
What two calcium channels can cause contraction in vascular smooth muscle?
Leaky Ca channels
L-type slow Ca channels
What are the steps of vascular smooth muscle contraction?
Ca++ entry –> Combines with calmodulin –> Binds to MLCK –> MLCK is phosphorylated –> Increases cycling rate of myosin head –> Contraction
Activity of vascular smooth muscle is dependent on ____ levels? (Not calcium)
Nitrate
Do nitrates stimulate or inhibit vascular smooth muscle contraction?
Inhibit
What are the steps to relax vascular smooth muscle within the NO pathway?
Sheer stress –> Arginine converted to NO via eNOS (Endothelial Nitric Oxide Synthase) –> increase in cGMP –> can be broken down by PDE (PDE can be inhibited by some drugs, i.e. sildenafil) –> If not broken down, increases activity of protein kinase G (PKG) –> Relaxation
Note: Schmidt says it phosphorylates MLK, but in the picture is shows that it takes a PO4 off, little discrepancy but let’s just go with what he said..
If you slow down the activity of PDE, would it cause more or less relaxation?
More - longer effect of cGMP and PKG which leads to relaxation.
Other than MLC, what other target does PKG have? What does it do?
Calcium entry channels. PKG phosphorylates the calcium entry cells, leading to closure of the calcium channels. This reduces the amount of calcium entering, which eventually leads to decreased contraction.
What can increase eNOS activity?
Acetylcholine or bradykinin
When acetylcholine/bradykinin binds to mACh-R in endothelial cells, what happens?
Release of calcium from calcium stores within the ER –> Interacts with calmodulin molecules –> Shape of calmodulin changes –> Increased activity of eNOS –> Increased NO –> interacts with soluble guanylyl cyclase –> takes GTP and turns it to cGMP –> Increased cGMP/PKG –> Relaxation due to decreased phosphorylated MLC and decreased Ca entry
Is cGMP stable or unstable?
Unstable; it will fall apart on its own.
If cGMP falls apart, does it have the same effect on PKG?
No
What speeds up the degradation of cGMP?
Phosphodiesterase (PDE); the more we have, the faster cGMP will be broken down. Inhibiting cGMP will extend the lifespan of cGMP, leading to prolonged relaxation of vascular smooth muscle cells.
What is an example of a PDE inhibitor that prolongs cGMP within vascular smooth muscle?
What’s special about this drug?
Sildenafil; increases cGMP, increases activity of PKG, leads to relaxation
It makes the elderly very happy, and apparently the elderly are thieves when it comes to drug trials.
What was the drug trial initially for (sildenafil)? What fun side effect did it have?
Pulmonary HTN
Sexual enhancement of male members; study was shut down
Do people know that they have pulmonary HTN?
Usually not for 20-30 years, but by then it is end stage.
In smooth muscle, are Ca leak channels enough to cause an action potential?
No; may cause tensing up, but not an action potential.
Is an action potential needed for smooth muscle contraction?
No
Is calcium always needed for smooth muscle contraction?
No; Ca usually kicks off contraction, but it can be caused by other compounds without Ca.
A smooth muscle action potential that occurs every 10 seconds would be indicative of what kind of smooth muscle?
Intestinal wall smooth muscle
Why do stomach cramps wax and wane?
They wax and wane every 10 seconds or so from smooth muscle activity; similar to intestinal wall smooth muscle
Another name for intestinal wall contraction every 10 seconds is _____
Pacemaker activity
What does the typical smooth muscle action potential look like? What is it elicited by?
A spike
External stimulus
What would the action potential look like of a muscle fiber within the uterus? What is it mediated by?
Upstroke, plateau, slow reset period; 0.3 seconds
Mediated via slow Ca channels
How do alpha 1 agonists work to contract smooth muscle?
Agonist binding to A1 receptor –> GDP turns to GTP –> Activation of phospholipase C –> Produces DAG and also takes phosphatidylinositol(spelling) from the cell wall and converts it to IP3 –> IP3 releases stored calcium from the ER –> Interacts with calmodulin to activate cross bridge cycling of the myosin head –> Contraction
Does DAG increase PKC?
Yes
Can serotonin constrict brain blood vessels?
Yes
What pathway does serotonin follow to constrict brain vessels in the brain?
Alpha 1 receptor agonist pathway
What is the only neurotransmitter that can constrict brain blood vessels?
Serotonin
Do the brain blood vessels respond to circulating catecholamines? Why?
No
If you had a SNS response, you don’t want brain blood flow to decrease while you’re running from a tiger, otherwise you wouldn’t run very good..
Why are SSRIs useful for headaches?
Increases tone in brain blood vessels, reducing pressure on areas prone to headaches
Beneficial in both the cord and the brain
What is cardiac muscle similar to in regard to sarcomere arrangement?
Skeletal muscle
Where does calcium hang out outside of the cardiac muscle cell?
Inside the T-tubule. Makes it easier to enter as it’s concentrated in one location.
What kind of smooth muscle has a more developed SR?
Cardiac smooth muscle
Where does the majority of cardiac muscle calcium come from?
Within the SR
What has to happen before Ca++ can be removed from the SR within cardiac muscle? What is this referred to as?
Calcium has to enter from the outside of the cell.
Calcium induced calcium release
How much calcium is coming in to the heart from the outside compared to inside?
80% from the SR
20% from outside the cell
What kind of calcium channels allow calcium to come in on cardiac muscle?
T-Type Ca channels (Fast Ca channel; faster to open/close than L-Type Ca channels)
L-Type Ca channels (slow, open after T-Type channels)
What triggers fast calcium channels to open within cardiac muscle?
Na mediates the cardiac action potential, which triggers calcium entry (T-Type first, then L-Type)
What are the three ways that calcium can be removed from the cardiac muscle cell? What are the ratios regarding where the calcium goes?
Ca/Na exchanger (3Na in, 1Ca out)
Ca ATPase pump (Uses ATP)
Tucked into SR by SERCA pumps (uses ATP)
80% Ca++ tucked into SR
20% Ca++ removed through the cell wall
What is the primary pathway for calcium to be removed from the cardiac muscle cell through the cell wall?
Na/Ca exchanger (3Na in, 1Ca out)
After the Na/Ca exchanger removes calcium, how is excess sodium removed?
Na/K ATPase pump (uses ATP)
What is another name for the Ca/ATPase pump? Is it used at the beginning or the later parts of removing calcium from the cardiac cell?
Calcium membrane calcium channel (PMCA)
Later parts of pumping the calcium out.
Within skeletal muscle, how is calcium taken from the cell and put into the SR? How does this help the SERCA pump?
Calsequestrin binds to Ca++ and pulls it into the SR.
This takes Ca++ out of solution, removing the effect of Ca++ concentration within the solution. This helps make it easier for SERCA to pump.
Where is Calsequestrin found?
Within the SR of any muscle cell.
What inhibits the SERCA pump? Is this found within smooth or skeletal muscles? Where is this found?
Phospholamban
No
Cardiac muscle
What does Phospholamban do? What is the result?
Inhibits the SERCA pump.
Calcium stays in the sarcoplasm for longer, giving a longer contraction.
What would a phospholamban inhibiter do?
Inhibit phospholamban, leading to Ca++ being tucked into the SR faster, resulting in a shorter contraction; cell would reset faster and be ready for another heart beat a little faster.
What receptors antagonize each other on the heart? How?
Adrenergic receptors and ACh receptors
More ACh = slower HR
More Epi = faster HR, stronger contraction
What is the effector protein between adrenergic receptors and ACh-R on the heart?
Adenylyl cyclase; cAMP dependent relationship
What does cAMP work similarly to?
cGMP (cyclates something)
What does cAMP do to PKA activity within the heart? What does that do?
Increases PKA activity
Leads to stronger contraction, & faster reset of the cell (increased HR)
If the ACh-R is activated, what happens?
Adenylyl cyclase is inhibited –> Reduced cAMP –> Reduces activity of PKA –> Reduces HR and force of contraction
Is the physiologic antagonism demonstrated between adrenergic receptors and ACh-R on the heart the same as mACh-R K mediated inhibition?
No; completely different system.
Where are mACh-R attached to K channels found in the heart?
Typically found on nodal pacemaker cells
Where are adrenergic receptors/ACh-R connected to adenylyl cyclase located on the heart?
Throughout the heart; not on nodal pacemaker cells
Lateral inhibition uses what kind of nerve fiber?
Type A beta
Lateral inhibition uses what kind of nerve fiber?
Type A beta
