Test 3 ☠️ Flashcards
skeletal/smooth muscle
Where does the spinal cord transmit sensory information?
Spinal Cord transmits sensory information from the periphery of the body up to the brainstem, cerebellum, and brain
Another term for sending portion of the central nervous system:
Efferent pathways: send signals from brain and spinal cord to rest of body
What is the function of efferent pathways in the spinal cord?
Spinal cord uses efferent pathways as a path to talk to skeletal muscles
What directions do motor and sensory info travel in the spinal cord?
Sensory info travels up the cord
Motor info goes down the cord
Which pathways take up most of the real estate in the spinal cord?
Ascending sensory pathways–larger than motor pathways
Lots of sensory info to pass to brain and brainstem
What are some examples of signals that get sent through ascending pathways in the SC?
pressure, temperature, vibration, pain
Where are cell bodies located in the grey matter?
Anterior horn of grey matter
What is the function of the grey matter?
Decision making
Lots of synapses, cell bodies, and connections that are in grey matter of spinal cord
Where do all efferent signals have to pass through if wanting to talk to peripheral target?
The brainstem
What is a tract?
A bundle of axons within the CNS
What are nerves?
Bundle of axons in PNS
Why do spinal cord transmission names end in tract?
They are pathways of axons bundles together in the CNS
Why do we need crossover in the spinal cord?
Left side of CNS controls function of the right side of the body and vice versa
What are the 5 categories of spinal tracts?
1) Pyramidal Tracts
2) Extrapyramidal Tracts
3) Dorsal Column Medial Lemniscus pathway
4) Anterolateral System
5) Spinocerebellar Tracts
How many pyramidal tracts are there?
(2)
-Lateral corticospinal tract (primary)
-Anterior corticospinal tract (secondary)
What is the function of the pyramidal tracts?
Primary motor commands
Majority of motor function
Voluntary movement
Why are they called Pyramidal tracts?
The signals pass through the pyramids in the brainstem
What is another term for lateral corticospinal tracts?
Primary descending motor pathway
What is the route of primary descending motor pathways through the spinal cord?
Signal originates in motor cortex (frontal lobe)
On way down passes through internal capsule
Through brainstem where pryamids of medulla are (crossover happens here)
Info is then passes down the cord via Lateral corticospinal tracts
Motor neuron in anterior horn is activated
Where is crossover for primary descending motor pathway?
Medullary pyramids
Where are the pyramids of medulla located?
anterior part of the brainstem in the medulla
Area where primary motor signals cross over from one side of the brainstem to the other:
Pyramidal decussation
What does the pyramidal decussation look like?
Crosshatched patterned tissue on the anterior part of the brainstem where the strands of neurons cross over
Bridges gap between left and right pyramids
After crossing the pyramidal decussation, where does the primary motor signal go?
Has to get to target
Descends laterally in the cord in the lateral corticospinal tract
Why is the tract called “lateral corticospinal tract”?
Lateral–pathway is in the side (lateral) parts of spinal cord
Cortico–signal originated in motor CORTEX
How does the lateral corticospinal tract allow for excitation of motor neurons?
Once signal reaches level its targeting for excitement, a little part extends into anterior horn and excites the motor neuron associated with it
What does the lateral coritcospinal tract include?
Pathway where the signal is traced down the cord to the motor neuron in the anterior horn
What percent of motor function is the lateral corticospinal tract (primary descending motor pathway) responsible for?
80% (4/5) of motor function
Why is the primary descending motor pathway larger than the other descending pathway?
Larger in size because there are a lot more neurons
Tissue is larger than some of the smaller secondary pathways
What is another name for secondary motor pathway?
Anterior Corticospinal tract
Where is the secondary motor pathways located?
Front (anterior) part of spinal cord
How does the size of the anterior corticospinal tract compare to the lateral corticospinal tract?
Anterior corticospinal tract is smaller
Carries a lot less information
What precent of motor function is the anterior corticospinal tract responsible for?
17% of motor function
What is the main difference between secondary and primary motor pathways?
Cross over area
Crossover in secondary pathway happens much lower than primary
Secondary cross over is at level of the cord where neuron needs to innervate target
Where does crossover happen in the secondary motor pathway?
Signal travels down same side of body that signal originated–crosses over at the level of motor neuron it needs to talk to
How does the signal travel in secondary motor pathway?
Signal originates in cerebral cortex (motor cortex)
Signal travels on same side of body through spinal cord on the way to talk to skeletal muscles
crosses over at level of motor neuron needs to talk to
What precent of motor information does not cross over at all?
2-3%
Signal will descend on same side it originated and never cross over
What are Extrapyramidal Tracts?
Accessory motor pathways that help coordinate complex tasks
Located outside pyramidal tracts
What type of motor function are extrapyramidal tracts responsible for?
Involuntary: helps us fine tune motor commands
We dont have knowledge of theses things functioning
control or feedback on instructions
What are the 4 extrapyramidal tracts?
Rubrospinal Tract
Reticuluospinal tract
Olivospinal Tract
Vestibulospinal Tract
What are the main ascending pathways?
1) Dorsal Column Medial Lemniscus pathways (DCML)
2) Anterolateral system
3) Spinocerebellar tracts
Where is the dorsal column medial lemniscus pathway located?
1 set of ascending sensory pathways–sits in back of spinal cord
medial lemniscus refers to structure that passes through as info is sent to brainstm
What type of info is transmitted by the dorsal column medial lemniscus pathway?
Transmits info regarding pressure sensors in skin
Major pressure sensory/ touch sensory pathway
-fine pressure
-fine vibration
-all sorts of sensory things
Where does cross over happen in the DCML pathway?
Medulla–usually one of 2 routes to get to medulla
What route does the DCML pathway use to get information to medulla for cross over?
Touch sensation comes into cord
Enters dorsal rootlet
Portion if touch info fed into grey matter in the cord
Other portion of info hops into dorsal column and rides up to the brain
In the DCML pathways, what happens to the information that is fed into the grey matter?
Info that goes into grey matter usually stays in grey matter and does not ascend
What is the purpose of sensory info remaining in the grey matter in the SC?
Info can be involved with lateral inhibition (modulation of some activity in the cord)
What is transmission speed for DCML pathway and why?
Capable of very fast signal propagation
A fibers through DCML pathway
Which A fibers are involved in DCML pathway?
Variety of A fibers (alpha, beta, delta, gamma)–all myelinated
How does location of cord correspond to size of DCML pathway?
The higher up in the cord, the larger/wider the dorsal columns
The higher up= more sensory info being fed into cord (upper and lower extremities)
At which level would the dorsal column be the widest?
A) C3
B) T10
C) L1
A) L1 and T10 are near the end of the cord–info coming from lower extremities fed into dorsal column–only has lower extremities info fed into dorsal column
Which pathway is touch perception fed through?
Dorsal column medial lemniscuc pathway
ex: helps figure out if holding on to something
What are the 2 sections of the DCML?
Fasciculus Gracilis
Fasciculus Cuneatus
What is the Fasciculus Gracilis responsible for?
Part of DCML pathway that carried sensory info from the lower extremities
Where is the Fasciculus Gracilis located?
Located in very inferior section of the spinal cord
What is the Fasciculus Cuneatus responsible for?
Lateral part of dorsal column–upper extremity sensory information
Where is the Fasciculus Cuneatus located?
As more info is being fed as we go up the SC–it adds to the lateral side of the dorsal column
Where in the spine would you expect to see a lateral portion of the dorsal column?
Sections of the cord higher up in the neck–should have area of dorsal column that corresponds to all sensory info coming from upper extremities
Is the DCML pathway difficult to activate?
DCML pathway is very sensitive
Able to pick up very small changes in pressure
How does signal flow if you were to have sensory info start at your foot?
Tickle foot
Sensory info passes through dorsal root into dorsal root ganglia into dorsal column
Since sensation is coming from low area–send through fasciculus Gracilis pathway up the spinal cord
info is ascending on same side it came in until it gets to medulla (crossover)
Info then passes through structure in brainstem called medial lemniscus
Then info sent to thalamus to the ventrobasal complex of thalamus
Then to internal capsule to parietal lobe
What is the purpose of the ventrobasal complex of the thalamus?
In charge of running info from DCML up to parietal lobe
What is the internal capsule and where is it located?
Sits just outside the thalamus (between thalamus and parietal lobe)
above ventrobasal complex
Provides a path for info on the way to the parietal love
What is another term for parietal lobe?
postcentral gyrus
What is another term for topographical layout showing which parts of the brain process different parts of the body?
Homunculus
What does the top part of the parietal lobe process?
Lower extremity info
What does the middle part of the parietal lobe process?
Trunk info
What does the posterior to trunk part of the parietal lobe process?
Upper extremity info
What does toward the back of the parietal lobe process?
face
What effect would a stroke affecting the top part of the parietal lobe have?
Messed up sensations in lower extremities
Region of brain injury determine what part of the body is affected
The hands have a lot of pressure sensors. How is this represented when looking at the parietal lobe?
Areas in the body that have lots of pressure sensors (hand/face) have larger areas in the brain that process those signals
Its a lot of information to process
What is necessary to have detailed/sensitive information perceived by parts of the body?
In order to have really detailed info from any part of the body we need to use lots of different types of pressure sensors
Areas in the body with lower density sensory receptors are taken care of by __________ portions of the parietal lobe.
smaller
EX: trunk–doesnt have very dense sensory receptors so hard to tell where someone is poking you in back
What are the 2 parts of the anterolateral system?
Anterior spinothalamic tract
Lateral spinothalamic tract
What is the anterolateral system responsible for?
Transmit pain signals up to brain through thalamus
What are the 2 paths pain can follow?
Fast pain signal
Slow pain signals
Why are pain signals called “spinothalamic”?
Corresponds to the fact that pain signals are going to go into the cord (within the spine) and usually relayed through the thalamus then out to parietal cortex
What are 2 interchangeable terms to describe pain pathways:
Spinothalamic tracts
Anterolateral tracts
What are the 2 spinocerebellar tracts?
Posterior spinocerebellar tract
Anterior spinocerebellar tract
What is the path of spinocerebellar tracts?
Sensory tracts that send info from spinal cord up to cerebellum
How is the grey matter divided and named?
Rexed’s Laminae / Rexed laminae
How are rexed laminae organized?
In the grey matter numbered from back to front
Most dorsal part of the grey matter would be in the dorsal horn
The most dorsal Rexed laminae:
Lamina I: first tip of dorsal horn
What is another name for Lamina I and what does it do?
Lamina Marginalis
known for being part of pathways that send fast pain up to the brain
Sent through A delta fibers
What is another term for pain fiber?
Nociceptor
What is the path that fast pain takes and which laminae is involved?
1) Fast pain comes in through dorsal root–>Dorsal rootlet into SC
2) Synapses on Lamina I
3) Signal crosses over to other side of the cord
4) Ascend into anterolateral pathway
First thing pain signal encounters is neurons that have cell bodies in lamina I
What is another name for Lamina II and III?
Substantia Gelatinosa
What is the function of substantia gelantinosa?
Important place for synapses in slow pain conduction
Where does slow pain synapse after entering SC through dorsal rootlet?
Slow pain synapses on cell bodies in lamina II, lamina III, and sometimes lamina V
How is slow pain routed?
Routed through non-myelinated nociceptors
C-fibers
Where does slow pain go after it synapses on lamina in dorsal horn?
After synapse, signal hops over to other side of cord and goes up via anterior spinalthalamic pathway (same as fast pain)
Where do mechanoreceptors synapse in the grey matter?
Can synapse anywhere from lamina I-VI (dorsal horn)
Where do mechanoreceptors feed sensory info?
Feed information into the grey matter of the cord
Where does the info from pressure sensors get routed?
Info is routed up through dorsal column
What are 2 ways motor neurons can be excited?
1) brain sending a signal
2) reflex arcs
Which lamina are associated with motor neurons?
Lamina VII, VIII, IX (located in anterior horn)
How many laminae do we have in the grey matter?
9
(lamina X is in the middle of the grey matter and deals with cross talk)
What is the function of the Rubrospinal tract?
Monitoring and adjusting voluntary movement
Modulation of voluntary movement
Similar to tracts that cerebellum uses
What is function of the Reticulospinal Tract:
Maintenance of underlying muscle tone in skeletal muscles
What is the function of Vestibulospinal Tract?
Helps maintain balance, monitors for changes in body positioning and rotational acceleration
Eye fixation/focus
Where is the descending pain suppression system located?
Located next to ascending pain pathway
How is the descending pain suppression system activated?
Activated in response to pain
Pain signal sent up to brain/brainstem sometimes activate descending pain suppression system
What is the function of descending pain suppression system?
Inhibitory in nature
Takes the edge off pain–doesnt usually completely suppress (it can but it usually doesnt) but runs in background to help body deal with pain
How many neurons are involved in the descending inhibitory complex (DIC)?
3 neurons:
Primary (1st neuron)
2nd order descending neuron
3rd order neuron
Where is the primary neuron (1st order) in descending inhibitory complex located?
Cell body in periventricular nucleus or periaqueductal grey
Where is the periaqueductal grey located?
Near cerebral aqueduct in midbrain of the brainstem
Where is the periventricular nucleus located?
Anterior to the periaqueductal grey: it front of the 3rd ventricle
What happens with the activation of the primary neuron in the DIC pathway?
Action potential is fired towards targets further down in the brainstem and spinal cord–enkephalin neurotransmitter is released
What happens to the 2nd order descending neuron when primary motor neuron is activated in DIC?
Primary motor neuron releases enkephalins–excites second order descending neuron to release serotonin
Where is the second order descending neuron located in descending inhibitory complex?
Cell body located in middle of the pons
What is the function of the second order descending neuron in DIC?
Serotonergic neuron–when excited releases serotonin
What is another name for serotonin?
5-HT
What neurotransmitter do second order descending neurons secrete and where do they do this?
Release serotonin in the spinal cord near the dorsal horn–acts on 3rd neuron in DIC
What is the name of the synapse from first order descending neuron in the pons?
Rapha Magnus Nucleus (RMN)
What is the function of the 3rd neuron in DIC and where is it located?
Very small enkephalin secreting neuron in the cord
How does the function of enkephalin differ from inside the cord vs in the brain?
In the cord enkephalin is inhibitory
In the brain enkephalin is excitatory
Where are enkephalin receptors located?
Located on nociceptors (1st order ascending pain neuron) and next neuron in ascending pain pathway (2nd order ascending neuron)
How does enkephalin affect nociceptors?
Nociceptor has dendrites in the periphery–info routed through dorsal rootlets into dorsal horn–and enkephalin receptor on it
When enkephalin binds to it, pain signal is shut down
Where does the 2nd order neuron in the ascending pathway synapse?
Lamina I, II, V
transmission would hop to other side of cord and ascend in anterolateral pathway
1st order ascending pain neuron:
pain receptor neuron
What is an inhibitory neurotransmitter in the spinal cord?
enkephalin
What is enkephalin?
endogenous morphine analog–all opiate receptors are enkephalin receptors
What makes up the endogenous opioid system?
Enkephalins and endorphins
What would happen if electrodes where implanted into periaqueductal grey area or periventricular nucleus?
Brain would be stimulated in those parts
Generate inhibitory pain signals–usually does not cause suppression just operates in the background and dulls pain perception a little bit
How can the DIC pathway be used with drugs?
Stimulate periventricular nucleus or periaqueductal grey areas to stimulate DIC pathway to reduce amount of perceived pain
What are some things that the body can sense as painful?
- damage to a nociceptor (crush or cut)
- Acidic conditions
- Elevated potassium
- Histamines
- Serotonin and acetylcholine in the periphery
- prostaglandins
- bradykinin
What is an example of acidic conditions that can lead to pain?
A build up of lactic acid in muscles from exercising
Why can elevated potassium be interpreted as pain?
high concentrations of potassium in the ECF can depolarize cells and it can be sensed as pain
Why are diabetics actually in pain and not just whiney?
If they haven’t gotten dialysis and their blood pH and potassium are screwed up then things are more painful
How do prostaglandins affect pain?
higher levels of prostaglandins make the sensitivity to things more severe
- if you inhibit the prostaglandins, you’ll feel less pain
What are the two types of medications that can be prescribed for chronic pain?
SSRIs and TCAs
How do SSRIs help with chronic pain?
it increases bioavailability of serotonin in the cord
- inhibiting the reuptake means there’s more serotonin in the synapse for longer
Tell me about TCAs –
- they’ve been around about 50-60 years
- went out of use because of the crappy side effects
- side effect is drowsiness, which could help you sleep if the chronic pain is making your mind overactive
What happens if pathways run parallel to each other?
- neurons close together can talk to each other
- neurons can shut down their neighbors
Why is it a good thing to have pain pathways running parallel to DCML/pressure pathways?
Because the DCML pathways can shut down the pain receptors - this is why your first instinct is to grab something when you hurt it
What is lateral inhibition?
when pressure sensors shut down pain signals
What is an example of lateral inhibition?
Acupuncture - putting needles in specific spots to deaden the pain signals
How does glutamate get released into the synapse?
Calcium comes in the cell through a voltage gated channel and interacts with the storage vesicles - it tells the vesicle to bind to the cell wall and dump it’s contents
What is the primary glutamate receptor?
AMPA receptors
How do AMPA receptors work?
It has a glutamate receptor connected to an ion channel - once the glutamate binds, it opens the channel and sodium floods in
What is the other main glutamate receptor?
NDMA receptor
What is different about NDMA receptors from AMPA receptors?
- they take longer to work - slower to open and slower to generate current
- bigger and able to let calcium in and a little bit of sodium
What are the two things an NDMA receptor need to open?
- neurotransmitter
- depolarization
What is blocking the NDMA receptors and why?
MAG
- the inside of a resting cell is negative so it pulls the mag closer to it, blocking the channels
- when the cell depolarizes, the cell becomes positive and pushes the mag away from it
- this is what causes a delay in these channels
What is a perk of having two different types of channels in the synapse?
Double the information can be sent
What is important to know about NDMA receptors through development?
As you get older, more NDMA receptors get planted in the synapse - you don’t have as many when you’re younger
What are some things that can block NDMA receptors?
- ethanol
- lead poisoning
- ketamine
- nitrous
- tramadol
How does ketamine work?
- it is a dissociative
- it only works on NDMA receptors, not AMPA
- it affects your perception of pain
- if it takes out the calcium pathway, it’s enough to keep us from registering pain
Why is tramadol a terrible drug?
- it doesn’t do much through the narcotic (enkephalin) receptors
- it somewhat has an SSRI affect
- may work in elderly or super sensitive people
- shouldn’t be used as a primary pain control post-op
What affect does chronic pain have on the receptors?
Chronic pain inserts more AMPA and NDMA receptors - the more they get activated, the more they populate in the synapse
- create more action potentials to make you more sensitive to pain
What are the 3 glutamate receptors Schmidt wants us to know?
- AMPA
- NDMA
- Kainate receptors
Which glutamate receptors are ionotropic?
AMPA, NDMA, kainate
Describe the typical pathway of the for pain (fast or slow):
Nociceptor (1st order neuron) in periphery senses pain
routes information through spinal nerve, dorsal root, dorsal rootlet
nociceptor has to synapse with second neuron
second neuron hops info to other side of cord via AWC
Pain signal is sent up through anterolateral columns
In typical pain transduction, where does the synapse occur?
Lamina I for fast pain
or
Lamina II/III/V for slow pain
Where is the second order descending neuron in the DIC pathway located?
Starts in the pons and stretches down to the spinal cord
moves inferiorly through the cord outside grey matter
When the 3rd order neuron in DIC pathway releases enkephalin, which side of the synapse is shut down? (pre or post)
Shuts down presynaptic and postsynaptic sides of the synapse
lowers activity in both neurons
what type of drugs can be used for managing pain transmission in the spinal cord and what do they target?
Enkephalin receptor agonist–targeting the enkephalin receptors (morphine receptors)
What happens at the cellular level with chronic pain?
Glutamate receptors are up-regulated and harder to inhibit with enkephalin analogs
enkephalin receptors are reduced and glutamate receptors are increased
What is another name for anterior spinothalamic tract and why?
paleospinothalamic tacts
older pathway not as developed as fast pain
What neurons are responsible for slow pain transmissio?
C-fibers
What neurotransmitters are involved with slow pain?
Substance P is the main neurotransmitter
CGRP
glutamate (not often but sometimes)
What is CGRP?
Calcitonin Gene Related Peptide–neurotransmitter that works in slow pain pathway
Why causes slow pain to be slow?
Neurotransmitters are slower to be released, slower to bind to targets, slower to generate changes in target membrane
slow transmission d/t non myelinated neurons
Glutamate in slow pain pathway:
slower to act and be released compared to fast pain
Difference in localization between fast and slow pain pathways:
slow pain–difficult to localize but can have general idea
fast pain–very localized
Where does slow pain terminate and what is this area known as?
Slow pain usually does not make it up to the thalamus (small portion can)
terminates at the top of the brainstem–reticular formation
Why is it difficult to localize slow pain?
Difficult to determine where pain is coming from since the signal is not processed in parietal lobe
What pathways is slow pain transmitted with?
pathways associated with thermoreceptors
hot, cold, vibration sensors
Where does slow pain synpase?
Synapses on lamina II, III, or V in dorsal horn of grey matter then crosses over and ascends via anterior spinothalamic tract
Which part of brain allows for localization of pain?
Somatosensory areas (parietal lobe)
Where is a portion of slow pain routed to that can increase perception of pain?
Slow pain engages more of the emotional centers of the brain
Where are the emotional centers in the brain located?
Emotional centers are very close to middle of brain around place where brainstem connects to diencephalon
True or False: Fast and slow pain have equal psychological effect on people:
False: chronic slow pain has more psychological effect on people compared to fast pain
messes with head
What neurons are involved in fast pain propagation?
A delta fibers (myelinated)
What is another name for pain sensors?
Nociceptors or free nerve endings
What is the primary neurotransmitter in fast pain?
Glutamate: fast to be released, fast to bind to receptor, and fast to generate AP in neuron
What is the mechanism of action of glutamate?
increases sodium and calcium permeability in the neuron
Where do fast pain signals get sent?
Parietal lobe–pattern that determines which part of the body is sensed in which part of the parietal lobe
What other info is fast pain routed up with?
Sensory info from DCML pathway
fast pain is transmitted to same part of brain that sensory info is transmitted to
Describe the path of fast pain:
Info comes in through dorsal rootlet
synapses on lamina I with second neuron
crossover at AWC
up lateral cord
fed into thalamus (ventrobasal complex)
info projected out to different parts of brain to interpret
Where is the crossover for fast and slow pain?
Anterior white commissure
Where does fast pain synapse?
Lamina I
What is another term for lateral spinothalamic tract?
Neospinothalamic tract: meaning “newer” pathway or recent branch off of slow pain pathway, more sophisticated than slow pain path
Term for old and term for new:
Old= paleo
New= neo
What are the 4 spinal reflex pathways we learned about?
Stretch Reflex
Tendon Reflex
Withdrawal Reflex (Flexor reflex)
Crossed Extensor Reflex
Which of the reflexes are involved in pain response?
Withdrawal Reflex
Crossed Extensor Reflex
What type of receptors are enkephalin?
GPCRs
What are enkephalin receptors linked to?
a potassium channel - when opiates hit the receptors, it opens potassium channels to make it harder to excite
What are alpha 2 receptors linked to?
potassium channels
What medications are alpha 2 agonists?
Xylazine (least specific)
Clonidone
Precedex (most specific)
What is the benefit to using alpha 2 agonists?
they don’t produce sensations upstairs - you get pain suppression and relaxation
How do volatile anesthetics work?
Increase potassium conductance - suppression in the synapse
Where is cox 2 used?
Within the first and second order ascending pain neurons
What does cox 2 do?
makes more prostaglandins that interact with PG receptors - increase sensitivity of the neurons
How does iNOS affect pain?
Nitric oxide synthase -
increases sensitivity of the synapse to painful stimuli
How does mag work in the NMDA receptor?
Suppresses activity - taking a supplement of it can help with chronic pain
- if you take too much you’ll be in the bathroom for hours per Schmidt
What are interneurons?
neurons that can be excitatory or inhibitory - they act as a bridge between sensor and motor neurons
- can also help with crossover in the cord
Which reflex is the simplest?
Stretch reflex
What is the main goal of the stretch reflex?
To keep the muscles at a constant length - applies to weight bearing muscles
Give an example of when you would use the stretch reflex
If you push someone on the forehead and push them backwards - the quad muscles stretch sensed by muscle spindle and send to cord for contraction of muscles being stretched to keep you upright
What acts as the sensor in the muscles for stretch reflex?
Muscle spindle (spring)
What is the antagonistic muscle in the stretch reflex?
The hamstrings - they would relax
How would you test the stretch reflex?
- Tap on the ligament underneath the patella
- Hitting the ligament pulls the patella down and lengthens the quad muscle
- Quad muscle should contract and foot kicks forward
What is the main goal of the tendon reflex?
To protect your body from massive amounts of pressure
- prevents your muscles from ripping out of the insertion points in the bone
Give an example of when you would use the tendon reflex
If you fall out of a tree and land on your legs - you will probably have broken bones, but the reflex engages and prevents your muscles from being pulled off the bone
What activity is occurring in each muscle group in the tendon reflex?
Contraction in the hamstrings
Relaxation in the quads
How do the interneurons work in the tendon reflex?
there are two
- one is excitatory - reflex activation of the antagonistic muscle
- one is inhibitory - inhibits activity in the motor neuron
What is the main goal of the withdraw reflex?
Withdraw the limb away from the source of pain
What are the muscle groups in the withdraw reflex?
- Activation of the flexor muscle group - hamstrings
- Antagonistic muscle set - relaxation of the quads
Why does the withdraw reflex activate a larger number of muscles?
Because responding to pain is more urgent and involves more levels of the cord
How do interneurons work in the withdraw reflex?
Allows the signal to be sent up 2 vertebra and down 2 vertebra through ascending and descending interneurons
Where are the interneurons located in the withdraw reflex?
Tract of Lissaur
- cell body is in the white area of the cord that is between the dorsal horn and the edge of the cord
Which reflex is the most complicated and why?
Crossed extensor reflex - it involves both sides of the cord
What is an example of using the crossed extensor reflex?
If you’re walking and stub your toe on furniture, it allows you to plant your weight in the opposite leg and withdraw away from the source of pain
Why does the crossed extensor reflex need interneurons?
To cross from one side of the cord to the other
What muscle groups are used in the crossed extensor reflex?
- Contracts extensor muscles - quads (planting side)
- Relaxation of antagonistic muscles - hamstrings (planting side)
- Withdrawing involves contracting the flexor muscle group (hamstrings) and reflexive relaxation of the extensor muscles (quads)
What are characteristics of mature nACh-receptors?
Only found at NMJ in adults
How many domains mature nACh-Rs have?
5 different domains:
-2 neurotransmitter binding domains: alpha and alpha 1 where ACh binds
-3 other subunits: epsilon, beta 1 and delta
What is the conductance rate difference between mature and fetal nACh-Receptors?
Mature nACh-R have high conductance: ions move at fast speed through channel
Fetal nACh-R are low conductance: ions move slowly through channel when open
What subunits differ between adult and fetal nACh-Rs?
Fetal receptors have gamma in place of the adult epsilon subunit
What population would you expect to find low conductance nACh-Rs in?
children and infants
Why do immature nACh receptors stay open longer compared to mature nACh receptors?
ACh falls off of adult receptors much faster than it falls off fetal receptors
Fetal receptors response to normal ACh is extended so channel is open for longer
What are alpha 7 ACh-receptors?
Receptors that are found in the CNS
Multiple ACh binding domains in addition to the normal 2
All subunits (5) are sensitive to ACh
What happens when the brain sends a signal to contract a muscle, but the muscle doesnt contract?
The muscle does not contract so feedback isnt sent back to the brain confirming contraction
Body responds by increasing expression of ACh receptors on skeletal muscle–usually fetal nACh receptors
Where does the CNS express fetal nACh receptors when motor response isnt sensed?
Fetal genes populate entire muscle instead of just at NMJ
What is the consequence of having immature nACH-R in areas other than the NMJ day to day?
May not notice an issue day to day–ACh is only being released at NMJ so it doesnt affect them too much
What happens if you give succinylcholine to someone with lots of fetal nACh-receptors?
It would affect the fetal ACh receptors that are populated outside the NMJ
larger area would be depolarized–tissues hemorrhage potassium
could lead to fatal arrhythmias (vfib)
How quickly are fetal nACh receptors populated when lack of response from motor neuron (ie stroke and cant move one side of body)?
Fetal receptors can be up-regulated within a few days of the injury
What is an example of a disorder that would benefit from CNS populating fetal nACh receptors?
Myasthenia gravis: would give more sites for ACh to bind to at NMJ
What are reflexes dependent on?
skeletal muscle contraction or relaxation
What is the purpose of sensors in skeletal muscles?
Feedback to CNS if muscle contracted like it was suppose to
What is another term for CNS output?
Efferent information
What is anther term for information transmitted to CNS from periphery?
Afferent information
Whats a good rule of thumb to see if you have a deep spinal block?
Check reflexes–if reflexes are not there then you probably have a deep block (not guarantee of pain block but a good assessment tool)
What is another name for enkephalin/opiate receptors?
mu receptors
Name for the area where motor neuron is in close contact with skeletal muscle:
Junctional Area
Area immediately outside junctional area:
Peri junctional area–activity at junctional zone can affect this area
Area further down the muscle past NMJ:
Post Junctional Area
no affect from what is going on at NMJ
What is the purpose of neuromuscular monitoring?
To see how well the nervous system can talk to skeletal muscles
Where do we put electrodes for neuromuscular monitoring?
Put the electrodes in an area with a bunch of motor neurons–located in nerves
apply current on top of the nerve
Explain how depolarization occurs with external electrode nerve stimulation:
Electrical current running between the 2 electrodes is negative d/t electrons on the outside of the neuron
Inside of the neuron is also negative
The polarity is gone and the inside of the cell becomes depolarized by removing the charge difference
What happens to a neuron if the charge on the outside is the same as the charge on the inside?
Neuron generates action potential–sets of VG Na+ channels to talk to skeletal muscle–if no block we expect to see twitch contraction
What influences electrical current in the heart?
All of the current on the outside of the heart cells
How much voltage is used to assess neuromuscular block?
supramaximal stimulus
What is the purpose of supramaximal stimulus?
Supramaximal stimulus recruits all motor neurons to generate action potential–lack of contraction is not from lack of activating enough motor neurons
Expect to see entire muscle activated
Good baseline to monitor changes
What is a single twitch response?
One impulse to see what happens at the muscles
What is Train of Four?
Repetitive stimulation
Different train of 4 responses depending on what type of drug used
What is the train of 4 frequency?
2Hz/ 2 second
Hz= something happening per second
so ToF involves 4 twitches
Describe ToF with Non-depolarizing muscle relaxers:
NDMR:
-twitches come back in stages
-not all twitches at the same magnitude
- 1st twitch much stronger than subsequent twitches
What is the ToF ratio?
B/A: when all 4 twitches are present
If we can get actual numbers to correspond with strength of each twitch–contraction can be expressed as a ratio
B: strength of contraction of 4th twitch
A: strength of contraction of 1st twitch
What would you expect to see in the ToF ratio in someone who is early on in recovery vs someone who is in the later stages of recovery after receiving an NDMR?
early: expect small ratio
later: Ratio getting closer to 1 as the drug wears off and pt waking up
What should ToF look like before paralytics if measured?
4/4 all equal height
What is tetanic nerve stimulation?
Repetitive high speed contraction
short period of time–more than 4 impulses to look at
What is post-tetanic count (PTC)?
Use a tetanic contraction then see what impulses the muscle generates a few second after
Used to assess the health of the synapse and whether the synapse is ready to fire another AP after a bunch of APs were just fired
What is DBS neuromuscular monitoring?
Double-burst Stimulation
not just one series of tetanic contractions
high frequency contraction for a few seconds then stop, then more high frequency contractions
What muscle is innervated by ulnar nerve stimulation?
Adductor Pollicis
What muscle contraction is expected from innervating ulnar nerve with a nerve stimulator?
Thumb comes foreword
pinky finger twitches
What instrument can be uses to get an actual measurement of how much twitch is generated?
Force transducers
Where are popular places to monitor neuromuscular blockade?
Ulnar nerve
Facial nerve
Peroneal nerve
Posterior Tibial never
What muscle is innervated by the facial nerve?
side of face innervates Orbicularis Oculi muscle around the eye–ophthalmic branch of facial nerve innervates that muscle
Characteristics of single twitch stimulation in NDMR:
Onset takes a few minutes to kick in and usually has a longer effect (half life varies per drug)
Characteristics of single twitch stimulation in depolarizing muscle relaxers (succinylcholine):
Fast onset (paralyzed within 1 minute) and short lasting
effects wear off after a few minutes (3 minutes muscle contraction is coming back)
Why is Succinylcholine widely used?
Fast onset (can give IM)
Short lasting
Cheap
Why is the first twitch stronger than subsequent twitches in ToF after giving NDMR?
Motor neuron and skeletal muscles are affected by NDMR
motor neuron: auto-receptor is blocked so the VP1 do not move to VP2 (they are not ready to excrete neurotrasmitter)
First contraction is strong because neuron had time to replace VP2 storage vesicles
after initial ACh release from first contraction–there are fewer VP vesicles ready to go to synapse
smaller twitches are a result of less neurotransmitter being released from the motor neuron
What is the name of the ACh receptor located on the motor neuron?
Alpha 3 Beta 2 receptor
-3 alpha subunits
-2 beta subunits
AKA neuronal receptor or auto-receptor
What ion flows through neuronal nACh receptors and what are they responsible for?
Na+ and some Ca2+
responsible for moving storage pools into ready release (VP1 to VP2)
How do NDMR effect the skeletal muscle?
ACh receptor antagonists: preventing end plate potential
block alpha subunit on skeletal muscle nACh receptors
Which side of the synapse is inhibited by NDMR?
Both sides of the synapse are inhibited
Which side of the synapse is inhibited by Depolarizing blocks?
post synaptic cell: Skeletal muscle
What would you expect on a ToF in a patient who received Succinylcholine 4 minutes ago? (if measuring strength of contraction with a force transducer)
should expect to see all 4 twitches returning at similar height (strength)
all 4 twitched recover evenly
Does Succinylcholine have an effect at the neuronal ACh receptor?
Succinylcholine binds to auto-receptor on neuron and stimulates opening–this would cause plenty of current allowing for VP1 to move to VP2 and no neurotransmitter shortage
at motor neuron Succs would cause increase ACh in ready to release pool
What is the minimum amount of ACh alpha3 beta2 ACh receptors need to open?
Need minimum of 2 ACh bound for channel to open (HE WAS CONFUSING ON THIS IN THE VIDEO SO DOUBLE CHECK ME)
How is Succinylcholine broken down?
Plasmacholinesterase (produced in liver) clears Succs from system over time
NOT broken down by synaptic acetylcholinesterase
What are L type calcium channels for?
They supplement the P-type channels
- some calcium current run through them
- they are not required for motor function
What happens if you have too many fetal nACh receptors?
they are located in the post-junctional area of the muscle - succinylcholine can attach and cause prolonged depolarization in other areas of the muscle cell
- leads to more calcium coming in and can cause muscle contraction
What is the risk of prolonged depolarization due to fetal receptors?
More potassium is being hemorrhaged out of the cell - can cause arrhythmias
What is an example of a muscle having more than one motor neuron?
Optic muscles - they have several motor neurons
How does succinylcholine affect the eyes?
Because you have several NMJs, you have more calcium coming in and cause more contractions - this can cause increased intraocular pressure
What is a risk of giving too much succinylcholine?
Putting too much pressure/stress on the optic nerve and causing blindness
How do the adductor pollicis and diaphragm differ in their response to paralytics?
- Adductor pollicis is not a critical muscle, so it is more sensitive
- The diaphragm is a critical muscle so it will take more paralytic to completely wipe it out
- the diaphragm is quicker to recover
What doses would you need to paralyze the adductor pollicis and diaphragm?
- Adductor pollicis = 20-40 mcg/kg
- Diaphragm = 90 mcg/kg (to completely paralyze)
What type of muscle is the diaphragm?
A SKELETAL MUSCLE with motor neurons
What nerve controls the diaphragm?
The phrenic nerve
What levels of the cord control the phrenic nerve?
C3-C5 keeps the diaphragm alive
If you see twitches in the adductor pollicis, what could this indicate?
It probably means that the diaphragm is functioning and the patient can breathe on their own
What percentage of receptors blocked does the 4th twitch disappear?
about 75-80%
What percentage of receptors blocked does the 3rd twitch disappear?
85%
What percentage of receptors blocked does the 2nd twitch disappear?
85-90%
What percentage of receptors blocked do all twitches disappear?
90-95%
What percentage of receptors blocked does head lift occur?
70%
- this means you’ll probably have all 4 twitches and the patient can breathe on their own
What is a ballpark of mA for supra maximal stimulus nerve stimulator settings?
50-80 mA
What are the two most important inhibitory neurotransmitters in the spinal cord?
GABA and Glycine
What is the purpose of GABA?
- Inhibitory in nature
- increases chloride conductance
- if suppressed, you’ll have overactivity of CNS
What does acetylcholine do in the CNS?
- increases awareness
- if blocked, it makes you drowsy
What happens if you inhibit acetylcholinesterase?
It will increase the amount of acetylcholine in the synapse - it would increase awareness
What medication is a good mACh receptor blocker?
Benadryl - also works on histamine
What disease could we use acetylcholinesterase inhibitors for?
Alzheimer’s - a stigmine can cross the BBB
How does Histamine work in the CNS?
Similar to ACh - it wakes you up
How does glutamate work in the CNS?
increases neuronal activity with increased concentrations
What happens with too much glutamate?
It can burn out your brain cells and they won’t be replaced
How does dopamine work in the CNS?
- Potent motor inhibitor
- in the pleasure and reward center
How is dopamine related to parkinson’s?
There is less dopamine being produced so the motor system is overactive
How is CNS activity related to acidosis and alkalosis?
Acidosis = reduced CNS activity
Alkalosis = increased CNS activity
When bicarb combines with acid, what does it produce?
Carbonic acid that disassociates into CO2 and H2O
How is calcium related to CNS activity?
More calcium = reduced CNS activity
Less calcium = increased CNS activity
How does acidosis lead to decreased CNS activity?
If there are more protons, they bind to negatively charged albumin and hog the real estate - this leads to more calcium in the ECF which leads to reduced CNS activity
How does alkalosis lead to increased CNS activity?
If there are less protons, there is more real estate on albumin for calcium to bind to - this leads to less calcium in the ECF which leads to increased CNS activity
What are the 3 main spinal arteries?
one anterior spinal artery and two posterior spinal artery
Where is the anterior spinal artery?
it hangs out in the anterior median fissure
What is the downside to the anterior and posterior arteries not connecting?
There’s no collateral circulation so if you have a blockage in one then it can cause more issues
Where are the posterior spinal arteries?
Because the posterior fissure isn’t big enough, the two arteries are on each side of the cord
What arteries feed the spinal arteries?
- Vertebral arteries
- Cerebellar arteries
- Radicular arteries (also called segmental or medullary)
Where do radicular arteries come from?
They branch off the intercostal arteries
What is the pattern for how the radicular arteries feed the spinal arteries?
There’s not one - it varies from person to person
- for every 5-6 levels in the spine, there may be one feeding the right or left side and could go to either the front or back
What else is the aorta responsible for supplying?
Big juicy arteries that feed the renal arteries or the mesentery
What happens if you cross clamp the aorta to repair an aneurysm?
It can cause ischemia in anything further south from where you’re clamping
How much tissue in the cord is the anterior spinal artery responsible for?
75%
How much tissue in the cord is the posterior spinal artery responsible for?
25%
On average, how many feed vessels are there for the anterior spinal artery?
- 2 in the neck
- 2-3 in the thorax
- 1-2 below the thorax
How much arterial circulation is the Great Radicular artery responsible for, and where is it located?
- 2/3 of arterial spinal circulation
- enters the left side (closer to the aorta)
- T10 is most associated
- T9-T12 in 75% of people
- Could be from T5 to L5
What is another name for the GRA?
Artery of Adamkiewicz
How do you calculate perfusion pressure?
MAP - ICP
What should a normal ICP be?
10 mmHg
What happens to blood flow if you have a high ICP?
it impedes blood flow in the brain and the cord
What happens to ICP when you cross clamp the aorta?
It can increase CSF pressure by 10 mmHg
What can you do if the cord is going to be ischemic for a period of time (from cross clamping)?
- Anything that reduces inflammation in the cord
- Drugs to slow down metabolic rate of the cord
What it ischemia re-perfusion injury?
When you suddenly restore perfusion to the tissues - the vessels are wide open and the body has a hard time managing all of the oxygen in the tissues at once
How can you prevent ischemia re-perfusion injury?
Release the clamp pressure slowly and monitor the patient’s oxygen levels
What are the two pathways in the spinocerebellar tract?
Anterior ventral cerebellar tract
Posterior dorsal cerebellar tract
What is the spinocerebellar tract used for?
to send sensory information to the cerebellum that helps with complex movements and coordination
What is the anterior ventral cerebellar tract used for?
Sends information regarding the activity occuring in the anterior horn and ascends toward the brain
What is the posterior dorsal cerebellar tract used for?
Sends information about the tendons and muscle spindle stretch sensors to help make decisions
What pathway does the anterior cerebellar tract take?
Travels to the superior part of the cerebellum through the superior cerebellar peduncle
What are some chemicals that the body perceives as pain?
bradykinin
serotonin
histamine
potassium
protons
acetylcholine
proteolytic enzymes
prostaglandins
Ischemia
What percent of body mass is skeletal muscle?
about 40%
What kinds of things do we use skeletal muscle for?
To get away from danger, to communicate, regulate body temp
What do skeletal muscles store for energy?
Glycogen - a very large chain of sugars stuck together
What is the function of ligaments?
Bone to bone connections
What is the function of tendons?
Connect bone to muscle
What are intermediate tendons?
Tendons that connect one muscle to another muscle
List the layers of a muscle from smallest unit to the largest:
Sarcomere –> Myofibrils –> Muscle fibers (cells) –> Fasciculous –> Muscle
What is a sarcomere?
The functional contractile unit of a myofibril - bands made up of thick and thin filaments
What are myofibrils?
Cylinders that contain contractile proteins (actin/myosin)
How does the amount of myofibrils relate to the function of the muscle?
Fine motor controls = less myofibrils for more precise control
Stronger muscle contraction = more myofibrils
What are muscle fibers or muscle cells?
Basic functional unit of the muscle - every muscle fiber has an axon
What is a fasciculous?
Grouping of more than one muscle cell
What is a muscle made of?
Many fasciculi grouped together
What is a motor unit?
Collection of one or more skeletal muscle cell controlled by a single motor neuron
What is the difference between type 1 and type 2 muscle?
Type 1 = slow contractions that can be sustained for a long time - red muscle
Type 2 = can produce alot fo force but not for very long - “fast twitch” - white muscle
What do type 1 muscles need more of?
Mitochondria and myoglobin
What is myoglobin?
Iron containing protein that helps oxygen unload from the blood into the muscles
- has higher affinity for oxygen than hemoglobin does
What do type 1 muscles appear red?
More myoglobin present
What are some examples of type 1 muscle?
Duck or geese breast meat - Geese can fly at 30,000 feet for a long time
Soleus muscle - weight bearing specialized for standing all day
What are examples of type 2 muscle?
Chicken breast - fly up to a low hanging tree but not for very long
Ocular muscles - need a fast reaction time to see things around us, but don’t do any heavy lifting
What type of muscle is the gastrocnemius?
A combination of type 1 and type 2 - most of the muscles in our body are a combination
What is the sarcolemna?
Cell wall of a muscle cell
What is the sarcoplasm?
fluid inside the muscle cell
What is the sarcoplasmic reticulum and it’s function?
Specialized version of the ER for muscle cells - located in proximity to the transverse tubules
- calcium is stored here and released with action potential
What are transverse tubules used for?
they run perpendicular and allow action potential to penetrate deep into the muscle to make sure the myofibrils are activated
What is the Z disc in the sarcomere?
Located at the ends of the sarcomere where the actin filaments wrap around to attach
What is the I band?
Band made up of only thin (actin) filaments - extends from both sides of the Z disc
What is the A band?
Band where the thick and thin filaments overlap
What is the H band?
Band that is only myosin and there is no overlap
- located between the A bands
What is titin?
The stretchy connective tissue that holds all of the sarcomere together
- it allows torsion without it falling apart
How does the contraction of a myofibril happen?
When there is space in the I bands, it gives it the ability to shorten the sacromere
- actin and myosin gets pulled together, pulls the Z discs together and causes a contraction
What is the sliding filament mechanism?
Actin and myosin pull on each other where there’s overlap to shorten sacromere and produce force
Why are skeletal muscles multinucleated?
They are really long and don’t have room for the bucket loaders and train tracks, so they have more nuclei placed throughout
- these nuclei can repair damage, building proteins, etc.
Why is ischemia in the muscle perceived as pain?
Build up of metabolic waste products like lactic acid can be painful and it cannot be cleared when the tissue is ischemic with poor perfusion
What are some examples of mechanical painful stimuli?
stretch
crush
stab
physical tissue damage
very high temps
Very low temps
What are the extreme temps that the body feels the temperatures as pain?
> 45 degrees Celsius
<5 degrees Celsius
Someone who complains of pain when getting their hair brushed is said to have a __________ pain threshold
Low
What is pain threshold?
How easy or difficult it is to elicit a painful feeling
What influences someones pain threshold?
Genetics
Environmental: pain exposure
What happens to pain threshold when someone has chronic pain?
Pain for long periods of time up regulates the sensitivity of pain transmission and reduces pain threshold
chronic pain is difficult to settle down (want to prevent chronic pain if possible)
How does membrane potential correspond to pain threshold?
If threshold potential is raised more positive–reduced likelihood we will experience pain
If threshold potential is lowered more negative–> increased likelihood we well experience pain
What is parietal pain?
Tissue pain–more superficial pain
well localized–sharp pain–occurs at the source of the pain
What type of neurons would be in parietal pain?
A delta fibers
If you has appendicitis, would if be beneficial to put pressure on your RLQ?
Yes, parietal pain has capability of lateral inhibition from tactile sensors
What is visceral pain?
Pure internal organ pain
dull/achy and poorly localized
Where is visceral pain felt?
pain is felt in different area in the body
referred pain
What type of neurons would transmit visceral pain?
C fibers
What type of pain are most organs capable of transmitting?
Visceral and parietal pain
Do organs have pain sensors?
Yes
What organs are incapable of transmitting visceral pain and why?
Lung soft tissue–does not have pain sensors
Liver–doesn’t have pain sensors
What area of the liver is sensitive to pain?
Liver capsule
Where would referred stomach pain be?
Couple of levels above umbilicus
Where would referred kidney pain be?
lower back
Where is visceral pain routed through in the nervous system?
Autonomic nervous system
What is an organ capable of dual pain transmission that we discussed in lecture?
The appendix
Where is parietal and visceral pain felt in acute appendicitis?
Parietal pain is felt in the RLQ where appendix is located
Visceral pain is felt in umbilicus region–level of T10
How is visceral pain transmitted?
Visceral pain fibers are routed through the sympathetic chain and fed into autonomic ganglia then ascends 2-3 levels and enters the cord via pain transmission pathways
Why would holding RLQ in appendicitis help?
Pain of decompression
when compressing it helps because there are tactile sensors in the skin that have ability for lateral inhibition
Common referred pain site from heart ischemia?
Pain radiates to left shoulder/arm
Why is heart pain referred to the left shoulder and not the right shoulder?
The right side of the heart is less prone to ischemia because it is lower pressure
the pain usually comes from ischemia on the left side of the heart
Where would you expect to feel referred pain if experiencing heart ischemia with high RVP and LVP?
Referred shoulder pain on both sides
Where is the limbic system located?
Deep in the brain, sits on top of brainstem
What structures in the brain make up the limbic system?
Amygdala
Hypothalamus
Cingular gyrus
Where is the cingulate gyrus?
Outside the corpus callosum buried in middle of brain
not part of somatosensory area of parietal lobe
What type of neurons are most motor neurons?
A alpha–large and myelinated
What type of neuron is muscle spindle information sent back to CNS on?
Large myelinated neuron
What type of neurons does DCML pathway use?
Anything from A alpha to A gamma– depends on type of pressure deep vs superficial
Neuron used for lateral inhibition/ grabbing painful area:
A Beta Fiber
Crude pain like nausea, cold, and aches are transmitted with which neuron:
C fibers
What would be the order of pain sensation if you hit your hand with a hammer?
Perceived pain–sharp pain–then dull achy pain that messes with your head
Are there pain sensors in the brain?
No pain sensors in cerebral cortex–but there are highly sensitive pain sensors around brain (ex: dura mater)
What is myosin made up of?
Long string of myosin molecules make up each myosin filament
What are the different parts of a myosin molecule?
Each myosin molecule is made up of 6 total chains
2 heavy chains
4 light chains
What part of the myosin molecule is made up of heavy chains?
Heavy chains make up the bulk of the myosin molecule tail
heavy chains are wrapped around each other in a spinal and are larger than light chains
What the the types of myosin light chains and their functions in skeletal muscle?
2 essential light chains: give myosin head it ATP activity–essential for normal function
2 regulatory light chains: not as important in skeletal muscle, can turn contraction on and off in some other muscles (ex: smooth muscle)
Where are the light chains located on the myosin molecule?
Essential light chains are further out on periphery
Regulatory light chains are next to each light chain on the inside
What do regulatory light chains on the myosin do in smooth muscle?
regulatory light chains determine the activity level of the myosin head–if a muscle needs to produce fast and strong contractions the regulatory light chains allow that to happen
they are usually phosphorylated to turn contractions off or on
How does myosin form a larger filament?
Tails of the myosin molecules wrap around each other to form the filament
tails provide a way for myosin molecules to fasten themselves to other myosin molecules
Where does myosin bind?
Myosin head has affinity for binding sites at the active sites on actin
How does myosin head get the energy it needs?
Myosin head has ATPase activity–it can burn ATP directly
What is Actin composed of?
2 different protein strands:
1 actin strand (F-actin)
1 tropomyosin strand (regulatory strand)
Where are the binding sites for myosin located?
F-actin strand contains active sites for myosin to bind
What is the function of tropomyosin strand of actin filament?
functions as a shield–if there is an inactive muscle that is not contracting the tropomyosin molecule is oriented in a way that covers up the active sites on the actin so myosin cant bind
How does the body move the tropomyosin to get skeletal muscle contraction?
Regulatory protein complex called troponin–3 proteins that are stuck to each other
What are the components of the troponin complex and their function?
Troponin C is fastened to troponin T and troponin I
Troponin I: troponin binds to actin
Troponin T: Binds to tropomyosin
Troponin C: 4 binding sites for calcium
What happens when calcium binds to troponin C?
When calcium binds to troponin C it twists troponin I and troponin T
this movement uncovers actin binding sites so myosin head can bind to them
Where are the binding sites for calcium in skeletal muscle?
Troponin C–when calcium is bound it alters how tightly the actin and troponin strands are wound together
Describes the steps and orientation of Myosin head in cross bridge cycling:
LOOK AT NOTES FOR DETAILS here is rough steps
1) resting myosin molecule head is perpendicular to actin with ADP and phosphate attached–actin active sites are hidden at rest
2) Calcium is added to the cell and binds with troponin C–tropomyosin is unraveled and actin binding sites are unblocked
3) myosin head binds to actin active sites and released a phosphate as it uses tension to pull on actin bringing sarcomeres closer together
4) myosin head orientation changes from perpendicular to bend from pulling on actin and ADP falls off
5) myosin molecule is stuck without ADP or Pi
6) myosin needs ATP to release from actin–ATP is metabolized to ADP and Pi and tension is restored to myosin head (ready for another cycle)
How does myosin head look when its in a ready to go/ resting state?
Myosin head perpendicular to length of myosin filament and its bound to ADP and Pi
What would happen to the myosin if the body has ATP deficiency?
2 things:
1) wouldn’t be able to reset myosin heads and limited ability to produce force
2) myosin heads would be stuck in the actin without pulling (would make muscles stiff) EX: rigor mortis
What is meant by “excitation and contraction” coupling?
Turning electrical event into an event that generates force
How is calcium liberated from SR in skeletal muscles?
DHP receptors sense AP and pull on SR gate to let Ca2+ out
Where are DHP receptors located?
Cell wall and t-tubules
Amount of contraction strength generated by a muscle is dependent on ___________ and __________?
1) surface area
2) interaction between thick and thin filaments
What happens to contraction if a sarcomere is over stretched vs under stretched?
Neither would be able to produce force for a contraction
over stretch= no overlap of actin and myosin
under stretch= no room for sarcomere to shorten
What is an example of sarcomere that is overly stretched?
never happens acutely in the body
can happen over time with the left ventricle–sarcomeres in heart are similar to skeletal muscle–as the sarcomeres in the heart are stretched out the walls get thinner and it produces less and less force–will eventually fail over time
What happens to force as over stretch is lessened?
force increases
Which letter would correspond with optimal length/stretch of sarcomere?
C
What holds skeletal muscles at optimal stretch point in normal anatomy?
tendons allow for the perfectly stretched resting skeletal muscles
What type of person might have under stretched muscles and why?
Athlete: muscles are more developed than average person–may be under stretched because tendons are not fastening them in an optimal position
What muscles does the Achilles tendon anchor?
Gastrocnemius and soleus muscles to the calcaneus bone
What happens when someone snaps achillies tendon and gets it repaired?
the muscle might not be in optimal stretch position
repair is usually done by stretching remaining ends and sewing together so the tendon will be overstretched and not as long as before
What part of the body do you expect the sarcomeres to be a little under stretched?
Ventricles in the heart at rest–they are stretched out more when blood comes in and do their job better
What is passive tension?
Outside force that stretched a muscle by pulling on ends of a muscle (outside tension)
What is active tension?
Force produced by the contracting skeletal muscle as a result from an action potential
If using a force transducer and a weight, then stimulate the muscle with electrical current, how would we be find the passive tension, active tension, and total tension?
Passive tension would be the weight
total tension: measured tension when the muscle is shocked with the weight still suspended
active tension: total tension- weight
What would happen if a very heavy weight was attached to a muscle and then electrical current stimulated the muscle?
could cause overstretch on the muscle and not generate a contraction
How dose skeletal muscle load and contraction of velocity related to each other?
Important in the heart
lighter load= muscle can shorten faster
heavier load= longer time for muscle to shorten and more difficult for muscle to shorted
What happens to the heart if it is pumping against a high afterload?
High afterload= high BP
would take more time for the heart to eject blood–could lead to problems
What is quantal summation?
Recruiting more motor units to create more force–also larger motor units
What is voltage recruitment?
Voltage= depolarization
Strong voltage (lots of electrical activity)= tiggers more motor neurons
Weak voltage= may only recruit smaller motor neurons
What does temporal summation measure?
Force generated compared to rate of stimulation
increase rate doesnt allow for complete relaxation before next contraction
increased force of contraction d/t leftover Ca2+ in the cell up to 40Hz
What does Hz measure?
Number of stimuli per second
5Hz= 5 stimuli per second
With temporal summation, at what measurement does the stimulation start to become additive?
Past 10Hz –no longer have complete relaxation between contractions
Hit with another action potential before all the Ca2+ is put back into the SR
What has to occur for skeletal muscle to relax?
Calcium is put back into the SR in order to relax the muscle
What is Tetany and when does it occur in skeletal muscle?
Tetany–peak force skeletal muscle can generate (40Hz)
lose twitched in the measurement and have sustained contraction
calcium receptors are near saturation
In temporal summation up until what point can you expect to see individual contractions that are separate from eachother?
<10Hz there is relaxation between each contraction
Temporal summation uses supramaximal stimulus to start contraction–what happens if muscle is continually stimulated at a high rate?
Leads to tetany and can generate 3x more force than supramaximal stimulus
Explain Atrophy:
losing myofibrils when muscle is not in use for some time
if severe over time will lose skeletal fibers in addition to myofibrils
Is atrophy permanent?
not always–EX: limb in a cast will atrophy while not in use
What is skeletal muscle hypertrophy?
Expansion in cell size with increased muscle use
More myofibrils in skeletal muscle cells
vascular bed in muscle grows as well
What makes up a big part of skeletal muscle tissue mass?
Blood vessel network–grows with the muscle
What is hyperplasia?
A LOT of exercise for long amounts of time can generate extra skeletal muscle cells at very low rate
What are some potential beneficial drugs that would maybe help with regenerating skeletal muscle?
Drugs that turn on genes to increase skeletal muscle cell generation would be good for people with muscular issues
they would also increase all cell division because hard to target just one cell type–increase cancer risk
Can cardiac cells regenerate?
Yes, but very slowly
Wouldnt be able to regenerate enough after massive MI to fix that level of injury–but if there are little issues of ischemia at a regular slow rate the heart can generate new cells slowly to replace
What percent of our body mass is smooth muscle compared to skeletal muscle?
Smooth muscle: 10%
Skeletal muscle: 40%
Does smooth muscle have similar function throughout the body?
No, smooth muscle has a lot of variability (unlike skeletal muscle)
smooth muscle function depends on which are of the body it is in
How is smooth muscle more efficient than skeletal muscle?
Smooth muscle has slower cross bridge cycling
takes longer for smooth muscle myosin heads to release from actin–maintained force generated with out expending more energy
skeletal muscle is generating force but myosin heads are binding and releasing for every contraction so it takes a lot more ATP
Which type of muscle is stronger based off weight: smooth muscle or skeletal muscle?
smooth muscle is stronger than skeletal muscle on gram per gram basis
Explain the “latch” mechanism of smooth muscle:
ultra low energy state–very slow cross bridge cycling:
myosin heads do not release from actin and maintain the force that is generated for long period of time with very little energy use
How do smooth muscle cells compare to skeletal muscle cells in size?
smooth muscle cells are much smaller than skeletal muscle cells
What connects smooth muscle cells?
-Fascia/connective tissues
-gap junction
What is the ratio of actin to myosin in smooth muscle vs skeletal muscle?
smooth muscle: much more actin than myosin (10-20 actin: 1 myosin)
skeletal muscle: 2 actin: 1 myosin
Where does the actin anchor in smooth muscle?
Dense bodies–spherical structure
dense bodies can also anchor neighboring cells to produce force within the smooth muscle
Do smooth muscles have their own sarcoplasmic reticulum?
Yes but the SR is less developed compared to skeletal muscle
What are smooth muscles dependent on to get Ca2+ into the cell?
Dependent on outside Ca2+ coming into cell through leaky channels, VG Ca2+ channels or ligand gated Ca2+ channels
What causes smooth muscle to have a little bit of resting tone?
Leaky Ca2+ channels
What would be the primary reason for low blood pressure in a patient with hypocalcemia?
No calcium in the blood so blood vessels do not have Ca2+ coming in to help the smooth muscle contract (no tone in blood vessels)
secondary—no Ca2+ to the heart for heart beat
Majority of smooth muscle in the body is this type of smooth muscle:________________
Visceral smooth muscle AKA unitary smooth muscle
What are the properties of visceral smooth muscle?
-functions as a unit (gap junctions)
-coordinated contraction through Na+ and Ca2+ coming through gap junctions
-what happens in one smooth muscle cell is relayed to the next through gap junctions
What type of smooth muscle lines hollow organs/ intestinal smooth muscle?
visceral smooth muscle (unitary smooth muscle)
The iris and ciliary muscle are examples of ______________ smooth muscle
Multi-unit smooth muscle
Graded control/ delicate control of smooth muscle is usually controlled via this type of smooth muscle:
Multi-unit smooth muscle—no gap junctions for ions to move between neighboring cells
True or false: Multi-unit smooth muscle allows for smooth muscle to contract as a unit
False:
-multi-unit smooth muscle cells are depended on neurotransmitter release which creates a graded and fine tuned response for small amounts of force
What type of muscle is the esophagus?
Hybrid between visceral smooth muscle and skeletal muscle
conscious control of esophagus
What are the layers of smooth muscle cells in small arterial blood vessels?
3 layers:
outer most layer: connective tissue called adventitia
middle layer: smooth muscle layer
inner layer: endothelium
What are other names for Inner layer, middle layer, and outer layer of blood vessels?
Tunica Intima= inner later (endothelium)
Tunica Media= middle layer (smooth muscle)
Tunica Adventitia/Externa= outer layer (conneective tissue layer)
Which layers of blood vessels have the most communication and how do they communicate?
Smooth muscle and endothelium
Tunica Media and Tunica Intima
Layers communicate through neurotransmitters or gases
How does myosin in smooth muscle differ from myosin in skeletal muscle?
skeletal muscle has a gap in the middle of the myosin heads
smooth muscle myosin heads are arranged so there is no gap in the myosin–so smooth muscle can shorted more than skeletal muscle
Which muscle has the ability to shorten more: smooth muscle or skeletal muscle?
Smooth muscle: a small amount of smooth muscle can cut its length in half or more with a strong contraction
skeletal muscles can get a lot of work done but only shortens a few cm max
How does acetylcholine behave in vascular beds and the intestines?
- Causes vascular relaxation
- Causes contractions in the small intestine
Where is activity determined in smooth muscle?
The regulatory light chains of the myosin head
How does a myosin head (regulatory light chain) get turned on in smooth muscle?
It is activated when it is phosphorylated
