Propogation of Electrical Signal, Neuro Flashcards
(160 cards)
1
Q
Depolarization
A
Typically is a process that turns on most electrically excitable cells.
Refers to a process where inside the cell is becoming more positively charged, so because it’s a deviation from the normal negative resting membrane potential we say that that is depolarized.
Changing polarity in opposite directions
2
Q
Hyperpolarization
A
The process that the body uses to suppress activity
Making the cell even more negative than it is usually at rest
3
Q
Repolarization & its affect on Na+/ Ca+ Channels (Think heart for Ca++)
A
The return back towards resting membrane potential.
This process is super important because repolarization is required for the resetting of the fast Na+ channels. We need to come back down to “near normal” Vrm before fast Na+ channels will reset, resulting in fewer Na+ channels involved in an action potential or no action potential at all.
This process is also very important in the heart with our L-Type Ca+ channels (slow).
**Dihydropyridine Ca+ Channel Antagonists work on L-type Ca+ Channels **
4
Q
Permeability of Cl- During Action Potential
A
-Cl- permeability is adjusted to hyperpolarize or suppress electrical activity in excitable cells
-This happens through GABA receptors in the nervous system. Cl- channels open in neurons, making the cell more negative, and thus more difficult to excite
5
Q
Action Potential & Positive Feedback Loops
A
An action potential is an example of a positive feedback loop. We have an initial stimulus that causes Na+ to come in, which then activates fast Na+ channels that allow more Na+ to come in. This process continues until the action potential spreads along the entire length of the cell
6
Q
Propagation of Electrical Signal (How an action potential spreads along the cell)
A
-Stimulus causes depolarization, triggering more fast Na+ channels to open.
- Action potential/depolarization waves spreads in both directions away from the area where it was initially stimulated (as long as there is room for it to spread).
-Can be a two way process as described above, or can have a one way process in some cells.
-Two way propagation is going to speed up the process of exciting the entire cell
-Repolarization typically happens in the same manner/pattern that the cell was depolarized
Ex. given in class: Electrode stuck directly on the muscle, shocking it.
7
Q
Skeletal Muscle & NMJ Connection
A
-Skeletal muscle (striated) and the motor neuron are two distinct figures.
-It is not a continuous structure. There is space that separates the two cells, and neurotransmitters are used to transmit the message from the motor neuron to the muscle.
-Brain or spinal chord makes the decision to contract a muscle. The motor neuron is activated somewhere along the spinal chord. That activation produces an action potential that moves from the brain and spinal chord all the way out to where the motor neuron and skeletal muscle meet.
A neurotransmitter is released from the motor neuron.
The skeletal muscle has neurotransmitter receptors on the neuro-muscular junction
8
Q
Stimulation Ex: Nicotinic ACh Receptor
A
-ACh is the neurotransmitter released from the motor neuron
-ACh binds to nACh receptors on the skeletal muscle (there are some nACh receptors in the brain as well)
-There are two ACh binding sites on the nACh-R, and both must be bound simultaneously for the channel to allow current through it
-nACh-R is a donut-shaped protein stuck in the cell wall. Lined with AA with (-) charges to repel (-) ions so that only positive ions flow in
-Once both nACh-R are bound, Na+ flows into cell
-Some K+ can leak out through these channels. Na+ typically knocks it out of the way
-Small amount of Ca++ also sneaks through the Na+ channel
-Initial current of Na+ through the nACh-R sets off the fast Na+ channels (next to nACh-R) –> depolarization
Robust system, there are significantly more Na+ channels than we actually need, so the skeletal muscle should always respond (normal physiology)
9
Q
Inhibition (Hyperpolarization) Example: Muscarinic ACh-R
ACh Mediated Hyperpolarization
A
-Located in the heart and smooth muscle of the lungs
-GPCR that mediates K+ permeability at the nodal tissue
-Named after a mushroom found in the rainforest
-Mediate and adjust pumping levels of the heart, as well as electrical activity of the heart by controlling how hyperpolarized the cell is
SA & AV Node: Action potential spreads from SA node -> atria -> AV node -> ventricles
The vagus nerve comes into contact with the pacing cells of the heart
R. Vagus nerve predominantly affects the SA node
L. Vagus nerve predominantly affects the AV node
The vagus nerve releases ACh –> binds to mACh-R on nodal cells -> GPCR changes conformation -> Alpha subunit communicates w/ K+ channels nearby and causes additional K+ channels to open (cell becomes more polar, hyperpolarized)
-Increased electronegativity causes the cell to be more difficult to excite, influencing how fast the pacemaker activity works in the heart
-ACh mediated hyperpolarization; this is how our body pumps the brakes on our heart rate. Otherwise, it would be beating ~110bpm.
-Blocking this with a muscarinic antagonist would mean that the alpha subunit on the GPCR does not activate the K+ channels, the K+ channels would close causing the Vrm to be more positive leading to a faster heart rate
10
Q
Pressure & Action Potential
A
-Physical pressure on a sensor causes a change in electrical activity
-When there is enough of a stimulus, the electrical activity at the sensor turns into an action potential. Typically these are repeated action potentials
How does this happen?
Pressure is applied to sensor –> pressure sensitive Na+ channels–> Na+ channel becomes flattened out, widened, and Na+ permeability is increased. Na+ comes in –>Vrm becomes more positive–> action potential is generated
This is a method the nervous system uses to “keep an eye” on what’s going on
11
Q
Action Potential & Several Types of Stimuli
A
-We will not generate an action potential unless the stimulus causes the cell to depolarize to its threshold
-Vrm and threshold are based on what type of tissue we are looking at (heart, skeletal muscle, or neuron)
-A weak stimulus, that barely passes the threshold, will have a delayed/slow action potential
-A strong stimulus will have a quicker/stronger action potential
12
Q
Action Potential in the Heart
A
-Longer action potential than we see in neurons (millisecond vs seconds)
-An action potential is going to be specialized to fit whatever role that cell is responsible for
-The action potential plateaus/ is sustained to allow the heart to pump efficiently
-This is due to the slow L-type Ca++ channels (will pick that apart in cardiac)
13
Q
Extracellular Ca++ Effects
A
-Ca++ tends to stabilize membrane potential and settle down irritable tissue
-Ca++ causes massive depolarization because of its high concentration gradient and its two positive charges
-Because of the high concentration gradient, Ca++ typically sits along the cell membrane in the ECF.
-Because of the large, clunky nature of Ca++, it limits the resting permeability of Na+ because it blocks the entrance to the Na+ leak channels
- Ca++ is inhibiting electrical activity of the cell at rest
What happens if we have hypocalcemia?
There will not be enough Ca++ to block the Na+ leak channels. The cell will become more positively charged, and depending on the type of cell, increasing that cell’s excitability. Or if the cell becomes significantly more positive, it may not work at all
14
Q
Extracellular Effects of Ca++ & Hyperkalemia
A
-High K+ in the ECF causes a decrease in the concentration gradient.
-Less K+ is leaving the cell, making the membrane potential more positive
-Ca++ can be given to block Na+ leak channels, making the cell less positive
15
Q
Motor Neuron, Skeletal Muscle, & Ca++
(Also, two important factors when the nervous system wants a skeletal muscle to contract)
A
Two important factors when the nervous system wants a skeletal muscle to contract
1. The action potential in the motor neuron
2. The action potential in the skeletal muscle
If there is not enough Ca++ surrounding our motor neuron, the membrane potential of the motor neuron will be more positive than they would be otherwise
Why is this a problem?
With really bad hypocalcemia, we expect to increased activity of the motor neurons that in turn increases the amount of contraction happening at our skeletal muscles.
We are not too worried about the direct effect hypocalcemia has on the muscle. What we are worried about is how this affects the activity of the motor neuron.
Trousseu’s sign is what we see with hypocalcemia
16
Q
Mg++
A
-Works similar to Ca++, but Dr. Schmidt does not have a good explanation for it
-Reduces the electrical activity of a cell
17
Q
Cl- & The Nervous System
A
-Cl- channels keep the brakes on the nervous system
-When there is increased Cl- moving into the cell, the membrane potential becomes more negative which hyperpolarizes the cell causing it to be more difficult to excite
-If we were to remove Cl- permeability from the nervous system, it would result in massive amounts of electrical activity within the nervous system resulting in seizures
18
Q
What Affects the Rate of Electrical Propagation?(Neurons)
A
Rate of action potential is affected by:
Length of the nerve: The longer the nerve, the longer it takes to send this information
Diameter of the nerve: A neuro wider in diameter will conduct an action potential quicker because there is less resistance
A small neuron will have more resistance and the action potential will travel slower
Insulation of the neuron (myelin sheath): Myelin is an insulating compound on the neuron. The higher the insulation, the faster the action potential spreads
19
Q
Myelin Sheath:
What is it?
A
-Made from sphingomyelin in the cell membrane
-Begins as a Schwann cell (PNS) or an Oligodendrocyte (CNS). Over time, it grows and wraps itself in a spiral around the neuron
-These layers become compacted, and the water that was initially in the cell gets squeezed out
-We are left with a lipid compound that has been wrapped around the neuron providing protection (less prone to crush injuries), speed, and efficiency
20
Q
Myelin Sheath: What are the support tissues? (Oligodendrocyte vs Schwann)
A
Glial Cells:
-In the CNS (CN II, Brain, Spinal Cord, Retinas) myelin is maintained and produced by Oligodendrocytes
-If we lose myelin in the CNS, it is very difficult for the Oligodendrocytes to replace
PNS (Everything outside the spinal cord) myelin is maintained by the Schwann cells.
Schwann cells can regenerate myelin in the PNS as long as its not “too bad,” or a “continuous problem”
21
Q
Myelin Sheath: How does this effect conduction?
A
-If a neuron needs to send action potentials quickly, it can add more fast Na+ channels in the cell wall.
-Another way to speed up transmission of action potential is to limit the amount of Na+ pumped out of the cell by the Na+, K+, ATPase pump
-Insulation around the cell can limit the amount of Na+ being let into the cell, but more importantly, it is not allowing the Na+, K+, ATPase pump to push out Na+
-This allows the Na+ to move forward along the neuron, making the action potential quicker, more efficient, and reducing the energy requirements of the neuron because it does not get pumped out of the cell until the next gap (Node of Ranvier) in the myelin sheath
22
Q
Myelinated Neurons: Why are they less prone to ischemia?
A
The myelin allows for action potentials to be more efficient by requiring less energy.
By having decreased metabolic demands, the neuron does not require as much direct blood flow
23
Q
Nodes of Ranvier & Saltatory Conduction
A
-There is a considerable amount of distance between each gap along the cell wall of the neuron
-Most neurons will have a very high population of fast Na+ channels within each node of ranvier
-The movement of the Na+ from one node to the next occurs in a jumping pattern, and this is referred to as Saltatory Conduction
24
Q
Nerve Blocks; Does a myelinated or non-myelinated neuron require more anesthetic?
A
A myelinated neuron requires more anesthetic during a nerve block because of the super high density of fast Na+ channels at the Nodes of Ranvier
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Demyelinating Diseases
-Optic Nerve: Our vision is going to be cloudy, can lose our peripheral vision
-Guillain-Barre: The body is generating antibodies to "stuff" that shouldn't be there (after a viral infection, new vaccine)
-MS: Demyelinating disease that affects our motor neurons
Causes: Genetics, infection (with crazy stuff that our body hasn't seen before), autoimmune
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How does demyelination affect the neuron?
-Our fast Na+ channels, VG K+ channels tend to degrade and disappear underneath the myelin
-There will be Na+,K+,ATPase pumps still in place where the myelin has degraded, meaning that Na+ is going to be pumped out of the neuro prior to reaching the next node of ranvier
-We will not be able to send signals. What happens if this is occurring in a motor neuron? Action potentials will not be able to spread, this can result in paralysis
-The neuron will not look normal and will not function normally
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Cell-Cell Signaling; Electrical Synapse
| What is it? How does it function? What are they made of?
-Located in some smooth muscle, the heart, and in a few neurons
-Six connexin proteins form two connexons
-Connexons in one cell wall will pair up with adjacent a second connexon in an adjacent cell
-This happens in "rows"
-There is a channel through the connexons that acts as a conduit for small ions
-The ions can move easily and very quickly through the connexons. This is a much faster process than the binding of a neurotransmitter
A downside to this is that the electrical current can move in both directions. In the heart, for example, this can cause re-entry arrhythmias
-These re-entry problems only exist because of electrical synapses. This would not occur with a chemical synapse
28
Electrical Synapses in the Heart
| What are they there for? What issues can this cause?
-There are many gap junctions in the heart to allow action potential to quickly spread
-In some areas of the heart, such as the pacing areas, our body intentionally has fewer gap junctions to allow for some delay
-An issue that can arise because of these gap junctions is that electrical current can flow both directions, allowing for re-entrant tachycardia
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Cell-Cell Signaling: Chemical Synapses
| What are they? How do they work?
-Electrical signal that is relayed via a chemical intermediary (neurotransmitter)
-The "target" on the receiving cell is going to define what the neurotransmitter does
Ex: ACh is inhibitory on the muscarinic receptors of the heart, and stimulatory on the nicotinic receptors of the skeletal muscle
-Presynaptic terminal: Sending cell
-Post-synaptic terminal: Receiving end
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General Nerve Fiber Classification
-A fibers: heavily myelinated (largest)
-B fibers: lightly myelinated
-C fibers: no myelination (smallest)
A Fibers are subcategorized into:
Alpha: Largest
Beta: 2nd largest
Gamma: Third largest
Delta: Smallest of A fibers
-Fiber sizes vary from 20 microns to 0.5 micron
-Important motor neurons (like for skeletal muscle) are going to be large and heavily myelinated
-Tickle, cold, warmth, are typically smaller and unmyelinated
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Neuron Structures
| What structures make up a neuron? How many neurons do we have?
-Cell body: Soma. Vrm ~-60mv
-Dendrites: Receiving ends, not typically myelinated, project from the soma
-Axon: Sending end. Specialized to send action potential quickly. Usually myelinated. The end of the Axon is presynaptic side of the next connection point
~100million neurons
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Post-synaptic neural connections:
Dendrites
-Dendrites are the signal-receiving end of the neuron. Not myelinated because they have so many connections. They can have excitatory or inhibitory connections.
Each "connection" is an individual synapse.
A neuron can connect with greater than 10,000 other neurons
-The Vrm will be less negative near an excitatory connection than the Vrm of the soma (~ -10mv, -20mv)
-Inhibitory connections will be more negative and more difficult to excite
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Postsynaptic Neural Connections
| Axon Hillock, Gaba
-Axon Hillock: Beginning of the Axon. There are only inhibitory synapses here. Vrm is about -70mv, -75mv This is how we pump the brakes on the nervous system.
Usually the receptors here are Gaba. Gaba receptors on the axon hillock increase Cl- permeability, and this is a key component of controlling the electrical activity of the central nervous system
If we removed all of the gaba, it would result in over-the-top levels of central nervous system activity (seizures).
ETOH is a Gaba receptor agonist. If someone has been consuming massive amounts of alcohol for 10-20+ years, they're not going to be producing their own Gaba. Take the alcohol away--> massive seizures & over activity of the CNS
We only have inhibitory synapses at the axon hillock because an excitatory connection would mean that we bypass the thousands of connections with other neurons.
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Glial Cells
| Which is more predominant, neurons or glial?
## Footnote
If you had a brain tumor, what type of cell would it be?
Neurons are the most predominant type of cell in the nervous system. They are not proliferative
Glial cells are proliferative, so if you have a brain tumor it is most likely some type of glial cell.
Macroglia cells:
-Astrocytes: Provide support for the BBB. The appendages of the astrocyte wrap around the endothelial cells and capillaries within the brain.
Maintain pH of CSF (buffer) and electrolyte balance of CSF
-Ependymal Cells: Cilliated. Produce CSF and circulate the CSF with cillia
-Oligodendrocytes/Schwann: Myelin-producing cells
Microglia: Smallest. Immune function in the CSF. Function as macrophages and are able to keep the CSF clean and free of debris.
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Types of Neurons: Mulitpolar, Pseudounipolar, Bipolar
| Locations & Purpose
-Multipolar: Decision-making cells; whether or not to fire an action potential. Lots of space to receive information
Ex: Motor neuron: Pain sensors are telling the motor neuron that something is painful, the motor neuron makes the decision to pull body part away
-Bipolar: Two projections off of the soma. Bipolar neurons are used in special organs. Do not need extra attachments because they are sensory neurons themselves
Ex: Photoreceptors in the retina that send messages through the optic nerve
-Pseudounipolar: Majority of the sensory cells that are in the spinal cord or immediatly outside the spinal cord. This cell body does not really make decisions. It basically exists as a place to build proteins and to support the rest of the structures
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Multipolar, Bipolar, Pseudounipolar Image
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Somatic Sensory Receptors (Types of)
| Pressure Sensors, Pain Receptors, Golgi & Muscle Spindle
-Somatic = Aware, "Sensible"
-Free Nerve Endings = Nociceptor; pain receptors
-Pressure sensors: (Na+ permeability)
Pacinian Corpuscle,
Meissner's corpuscle,
Golgi tendon apparatus: A sensor in which the body can figure out how the muscles & limbs are performing. Integrated into our tendons and skeletal muscle
Muscle spindle: Stretch sensors interwoven into our skeletal muscles that can confirm if that muscle has contracted or not
These are considered "mechanoreceptors." They're able to take some kind of physical environmental disturbance and turn that into an electrical signal that can be relayed to the rest of the body
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Somatic Sensory Receptors & Adaptation (Baroreceptor Ex)
Ex: Baroreceptors
Map is normally 100mHg; Baroreceptors should have some amount of Na+ flooding in, but this is our normal BP
If map increases to 150mmHg, the rate of action potential propagation would increase in the baroreceptors --> information is sent to the brainstem-> brainstem makes adjustments
If our map stays at 150mmHg for greater than 2 days; our baroreceptors become desensitized to prolonged hypertension and adapt to what they think is the new normal.
If our baroreceptors did not adapt, they would be extremely limited in their ability to respond to any additional changes from normal.
This is an example of slow adaptation.
Some sensors do not adapt at all. Some are fast, some are slow.
Reverse adaption occurs in some sensors- we stimulate something for a prolonged period of time, we become more sensitive to that stimulus
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Pressure Sensor/ Ball Example & how that relates to fast adapting sensors
We have fast adapting pressure sensors because the body is concerned with changes in pressure.
Ex: Holding a ball in your hand; pressure sensors do not need to continuously tell your brain that there is that same, consistent pressure in your hand. It does not help the nervous system accomplish anything or make any decisions. We are only concerned when the pressure changes; like loosening our grip and dropping the ball
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Susceptible to block?
Anatomy dictates whether or not the nerve bundles are easy to block
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Pain Receptors & Reverse Adaptation
-Free nerve endings or nociceptor
-The more stimulus these receptors are subjected to, the more sensitized those receptors become
-The worse the pain is, for longer periods of time, the worse the pain becomes
-It is very important to tackle pain before it gets out of control
-Creating a nerve block that prevents pain from even starting is a great way to manage pain
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Directional Nomenclature; Planes & Cross Sections
Superior/Inferior
Dorsal (Back) / Ventral (Front)
Anterior/Posterior
Medial/Lateral
Rostral (front and towards the top)
Caudal (Low and toward the rear)
These are typically used in neurosurgery
Distal (Further from the CNS)
Proximal (Closer to the CNS)
Sagittal: Left from right
Coronal: Anterior from posterior
Horizontal: Superior from inferior (magician's cut)
Oblique: Goofy or odd angle
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Brain:
Telencephalon- Cerebral cortex
Diencephalon- Thalamus: Important relay center, receives and sends information
Hypothalamus: Sensory area, control center for our osmoreceptors, infection sensors, body temperature regulation
Brainstem:
Midbrain, mesencephalon
Pons (olive shaped)
Medulla Oblongota
Spinal Cord
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Locate:
Cerebral hemisphere
Diencephalon
Brain stem
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Sulcus, Gyrus, Fissure
Sulcus: Groove
Gyrus/Gyri: Lump of neurons in supporting tissue
Fissure: Very deep groove
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Major Brain Divisions (Lobes and landmarks)
**Lobes:**
* Frontal: Where we do most of our thinking
* Parietal: Primary somatosensory cortex
* Occipital: Where vision is processed
* Temporal: Language comprehension, listening to music & figuring out what the lyrics mean
**Landmarks:**
* Central Sulcus: Defining groove that separates the frontal lobe from the parietal lobe. Main anatomical marker if dissecting a brain
* Temporolateral Fissue: It's name describes its function. It separates the temporal lobe from the parietal and frontal lobes
* Longitudinal Fissue: Separates the left and right cerebral hemispheres. Runs from the front of the brain to the back of the brain
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Left lateral side of brain
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Inferior view of the brain
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Coronal- Separating anterior from posterior
**Locate:**
Longitudinal Fissure
Temporolateral fissure
Corpus Callosum: Where crosstalk takes place
Cerebral Cortex
White matter- Myelinated axons, sending/receiving
Grey matter- Cell bodies, decision making neurons
* The grey matter is superficial, which is odd because the body typically protects important structures by making them "deep structures." One good thing about this location is that the blood vessels in the brain do not have far to travel to supply grey matter with nutrients
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Grey Matter & White Matter in the Brain
## Footnote
How is each protected? Blood flow to the area?
**White matter**- Myelinated axons, sending/receiving. Located deeper in the brain than the grey matter
**Grey matter-** Cell bodies, decision making neurons
* The grey matter is superficial, which is odd because the body typically protects important structures by making them "deep structures;" however, the main blood vessels in the brain are also superficial, meaning the blood does not need to travel far to supply the grey matter with nutrients
* If the grey matter hits the inside of the skull (concussion, head injury) the grey matter can be temporarily or permanently damaged
* The body's way of protecting the grey matter is by suspending the brain in CSF. The CSF gives us a bit of a buffer
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# What took place to get this view of the corpus callosum? Color?
Sagital, left lateral
We are looking at the inside of the corpus callosum. The only way we'd be able to see that is by cutting the brain in half with a saw. The corpus callosum is lighter in color because it contains a large amount of myelinated neurons
The cerebral hemispheres did not have to bet cut. Those can essentially be pulled apart because of the longitudinal fissure
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# Brain Subdivisions
Broca's Area: Word formation, speaking. This is more of a motor function, that's why it is in the frontal lobe
Wernicke's Area: Launguage, understanding
Motor cortex: Pre-central gyrus This is where we execute our motor function. Planning motor funtion happens in the frontal lobe
Somatosensory: Post central sulcus
Limbic system: Emotional responses to things that are happening around us. Happens in temporal lobe and throughout the brain
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# Spinal Cord Cross-section. Grey vs White Matter, Dorsal and Ventral Horn
**White Matter:**
Generally filled with myelinated axons
Function is to send/receive signals
**Grey Matter**
Non-myelianated neurons & cell bodies
Cell bodies are where decisions are typically made
Ex: A motor reflex to something that is painful. That decision is made in the spinal cord and typically is not routed up to the brain
* Dorsal Horns: Sensory information goes in here. The cell bodies that reside in the dorsal horn are sensory neurons. Easier to access for anesthesia
* Ventral Horns: Where motor information leaves the spinal cord
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# Where does crosstalk happen? What are these locations called?
**Locations to Find:**
Where does the sensory info go in?
Where does motor information leave?
Anterior side of the cord?
Posterior side of the cord?
Posterior median fissue
Anterior median fissure (what goes here?)
Dorsal horns
Ventral horns
**Central Canal:**Lined with cilliated cells, moving fresh CSF from the brain down the spinal cord until the cord terminates. Then the CSF is allowed to float back up to the brain
**Lamina X:** An area in the grey matter of the spinal cord where crossover takes place
**Anterior White Commisure (AWC)** An area anterior to the grey matter where crossover takes place. Commisure means connecting
These are the only two spaces in the cord where the left and right are able to communicate
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# Which blood vessels feed into the spinal arteries?
There is a large blood vessel that travels beneath each rib.
The intercostal blood vessels feed into the anterior & posterior segmental arteries
Another important area of blood flow comes from the top of the cord, just below the brainsteam
We have autoregulation of both brain & spinal blood flow that is very tightly controlled
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General Overview: Motor Pathway
Motor: (Efferent Signals)
A stimulus originating from the brain will need to go through deeper structures such as the thalamus. A portion of the information will have to go through the brainstem in order to enter the cord. Once at the level of the spinal cord, the stimulus exits through the anterior horn, down the anterior rootlets of the cord, and travels to skeletal muscles or motor targets
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# Afferent Sensory Pathway. How does the stimulus travel throuhg the cord?
-Sensory information travels in through the dorsal horns
-Motor information leaves the cord through the anterior horns
-The rootlets are segmented and attached with a horizontal approach. Sensory information travels through the posterior rootlets and enters the dorsal horn. From the dorsal horn, the information "jumps" over to white matter in the cord where it ascends the spinal cord, travels through the brain stem, and to the brain
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This is showing a generalization of where the ascending columns are
The majority of them are in the posterior part of the spinal cord, then the sides of the cord, and lastly the anterior portion.
Pain, pressure, and other sensory messsges are sent this way
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# Descending signals are primarily what?
These pathways are primarily motor. They are located in the lateral and anterior cord
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# The rootlets form what? And merge into which structure?
## Footnote
What makes up the spinal ganglion? What kind of information is received in the spinal nerve?
-The anterior roolets lead into the anterior root which merges into the spinal nerve
-Motor cell bodies are located in the anterior horn
-The posterior rootlets feed into the posterior root and form the spinal ganglion before merging into the spinal nerve
-The spinal nerve is where motor and sensory information meet. Most spinal nerves will have mixed motor/sensory function
-The spinal ganglion (located in the posterior root only) is a collection of cell bodies of our pseudounipolar sensory neurons
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# How many pairs of nerves at each level? Where do they exit?
-We have spinal nerves exiting the spine for each level of vertabra that we have
**-Cervical Spine: **7 cervical vertabrae. There are 8 pairs of spinal nerves, one coming out of the left and one coming out of the right. C1 spinal nerves exit above C1... ending with C8 spinal nerve pair exiting below C7.
The c-spine nerve pairs are named after the cervical vertebrae in which the originate ABOVE
**-Thoracic: **12 Vertebrae, 12 pairs of spinal nerves.
These spinal nerves originate BENEATH the vertebrae for which they are named
**Lumbar:** 5 lumbar vertebrae, 5 sets of spinal nerves, exiting the cord underneath the vertebra for which they are named.
Sacrum: Originally start off with 5 vertebra at birth. Fuse into one solid bone as we enter adulthood. 5 pairs of spinal nerves associated with each of the original sacral vertebra, exiting the spinal cord underneath the vertebrae they are named after
**Coccyx**: 1 pair of nerves, two distinct vertebrae. Nerves originate at the base of the spine.
We start off at birth with 4 distinct vertabrae
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# Dermatone Man
A dermatome is a region of the body that is innervated by a set of spinal nerves
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# What shape? Shock absorbers?
The spine follows an S-shaped patern in adulthood
There are discs in between each vertebrae that provide cushioning and some degree of shock absorption (springy)
This helps us when we're walking around all day, we don't really notice the pressures that are weighing on our spine
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# Physiologic & Pathologic Spinal Curvature
Cervical Spine: Lordosis
Lumbar Spine: Lordosis
Thoracic Spine: Kyphosis
Sacral Spine: Kyphosis
Lordosis: Anterior curvature, or if looking at from the front, convex curvture
Kyphosis: Posterior curvature
At birth, we typicaly only have kyphotic curvature. This is one reason why it's hard for newborns to balance their head. They have an off-balance center of mass. Anterior curvature is a crucial process in being able to walk
Pathologic Thoracic Kyphosis: the most common type of abnormal curvature. As we age, elder adults get the "hunchback" look. This destabilizes the overall structure and puts pressure points on some of these structures that are held within the spine itself
Scoliosis: Abnormal lateral curvature of the spine. Fairly common problem. Does not always need to be corrected surgically. Patient dependent; what's your lifestyle? How is this surgery going to affect you later on in life?
Kyphoscoliosis: Combination
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**Vertebral body: **Weight supporting structure of the spine. Our intervetebral discs sit on this structure. The higher up the spine you go, the smaller the vetrebral body becomes
**Vertebral arch:** U-shaped structure that extends off the vertebral body. Houses the spinal cord. Many proccesses (boney extension) extend off the arch.
**Pedicle:** First part of the arch coming off of the vertebral body
**Lamina: **The remaing part of the U. Connects the two pedicles together
**Spinous Process:** Palpable, gives anesthesia a good marker. Projection coming off the posterior portion of the vertebra
**Transverse Process:** Do not connect anything. Extend laterally from the arch
**Superior Articular Process:** Extends off the superior portion of the arch, connects to the **inferior articular process** on the vertebra above
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# Vertebral notch houses? What is the facet joint?
Inferior Vertebral Notch: Where the spinal nerve exits
Facet Joint: Where the superior & inferior processes connect. Lined with cartiledge
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# Where does the spinal cord go?
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# Specialized structures only found in the neck?
-Compound spinous processes. Two projections on the process **(Bifid)**
-C2-C5 is almost always bifid
-C6 is bifid 50% of the time
-C7 is bifid 0.3% of the time
-**Transverse foramen** located in the transverse process. Vertebral arteries run through here. There are two vertebral arteries (L/R) which of 2/4 arteries that supply blood to the brain. The vertebral arteries pass through the back of the neck. They are named because they pass through vertebral (technically transverse) foramens in the neck
-The vertebral artery does not pass through the transverse foramen in C7
-Tranverse notch/sulcus is where our spinal nerve passes through
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# What is different about C7?
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# Why is C1 different? How/where does it connect to C2?
-C1 has a specialized shape to provide a clean connection to the base of the skull.
-Also called Atlas. Supports the weight of the skull
-Atlas is a mythical god that held the weight of the world on his shoulders
-C1 has no vertebral body
-Anterior arch & tubercle in place of the vertebral body. The dens of C2 articulates to the posterior side of the anterior arch of C1
-Posterior arch & tubercle
-Superior articular facet is hollowed out, lined with cartiledge, connects with the base of the skull
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# What are the highlighted structures? 2 Ligaments that connect here?
-Foramen magnum: Cord & neck ligaments passe through this
-Occipital condyles connect to the superior articular facet of C1
-Occiptal bone
-Atlantoocciptal ligaments: Anterior & posterior; they connect the top of the spine to Atlas through the opening of the foramen magnum
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# Where is the base of skull resting? A pivot point does what?
-Pivot point gives us the ability to move our head back and forth to nod "yes"
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# Name of the specliazed structure? Purpose? Name of C2?
-Dens is located on the anterior side of C2, on top of the vertebral body
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-C2 does have a spinous process
-Anterior articular facet lined with cartiledge, thats what rubs against the posterior side of the anterior arch of C1
-Ligaments wrap around the posterior side of the dens
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# What is this?
-Dens of C2 connecting to C1
-There is flexibility in this connection point. It's an axis or the skull to rotate on. Basically a swivel attachment
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# Names & Purposes of ligaments
-These ligaments run continuously from the bottom of the sacram to the base of the skull
-Anterior longitudinal ligament: Anterior to vertebral bodies, very long and wide
-Posterior longitudinal ligament: Posterior side of the vertebral bodies
-Intertransverse ligament: Links the transverse processes together
-Supraspinous ligament: Directly on top of the spinous processes
-Interspinous ligament- Immediately deep to the supraspinous ligament. Connects the spinous processes together (sits between them)
**-Ligamentum Flava: Connects the anterior arches at each vertebral level. This ligament is stretchy and elastic. This feels different when approaching the cord with a needle. You will feel a change in resistance when passing through this ligament**
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# Name the ligaments
-Ligmenta flava is a different color to highlight that it is made of a different composition than the other ligaments
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# What did they have to cut/remove? What does the gap signify?
-Cut the pedicle and the anterior portion of the vertabra off
-The midline gap in the ligamenta flava is an incomplete fusion of the two sides of the ligament (most people have this)
This is significant because if you are taking a midline approach with a needle, you will not feel the change in resistance. Need to take an off-midline approach
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# What are the ligaments? One of them is an extension of whats?
-The nuchal ligament is an extension of the interspinous ligaments. "Expanded fan-like ligament"
-Anterior longitudinal ligament
-Posterior longitudinal ligament
-Supraspinous ligament
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# Atlanto-occipital ligaments? Nuchal? Nub? Delicate structures?
-Anterior atlanto-occipital ligament/membrane
-Posterior atlano-occipital ligament/membrane
These connect the arch of C1 to the posterior side of the foramen magnum
-External occiptal protuberance (nub): Where the supraspinous ligament & nuchal ligament connects with the base of the back of the skull
-Back of the head is delicate, ligaments are not enough to keep the skull intact if you dive into a pool with 1ft of water
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# Apex of dens? Body of Axis? Nuchal ligament?
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# T-Spine. What's different about it? Vertabrae connect to what?
-According to textbooks, the vertebral prominance is the spinous process of C7
-Reallistically, it's the spinous proccess of T1. It is larger, more prominent
-Spinal processes of T-spine are angled steeply & downward. Makes it difficult for anesthesia
-Kyphotic curvature
-12 vertabrae have connection points for our 12 ribs
-Having our T-spine connected to our chest/ribs makes it a very stable, robust, strong structure
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# Where do our ribs connect?
-There is a costal facet on each transverse process of the T-spine
-There is a costal facet on the superior and inferior portion of the vertebral body of the t-spine
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# Sternum components? Cartiledge purpose here? Rib classification?
-The costal cartiledge between the sternum and the ribs allow for some flexibility. This helps prevent crush injuries
-3 connection points for ribs 1-10
-True ribs: 1-7: Cartiledge connecting ribs directly to the sternum
-False Ribs: 8-10: These ribs are connected to the cartiledge of rib 7
Floating ribs: 11-12- Easy to displace or dislodge. Only have one connection point
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# Rib connection points? Cartiledge or bone?
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# Standard structures and unique structures?
-Downward angled spinous process
-Hard to insert a needle here
-Superior costal facet, inferior costal facet, transverse costal facet.
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# At which three points does the rib connect to the t-spine?
True Ribs:
-The head of the rib will connect to the superior costal facet, and the costal tubercle of that same rib will connect to the transverse costal facet of **one** vertebra.
-The superior portion of the head of that same rib will connect with the inferior costal facet of the verebrae above
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# Head & Neck of rib attach where? Difference btwn L/R vertebral body?
| t-spine
-Heart shaped vertebral body
-Left side of the body is compressed, flattened out due to the aorta
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# Head, Neck, Costal Tubercle
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# Lumber Spine Anatomy
-Vertebral bodies are large because they need to support a lot of weight
-Spinous processes are angled straight back posteriorly. Good place for us to do epidurals. Can have the patient lean forward if we need more space
-Fit the generic mold for vertabrae, no real specialied structures
**Intervertebral Foramen**
-Inferior vertebral notch
-Superior vertebral notch
Where spinal nerves exit
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# What age does this fuse by?
-Starts off as 5 individual bones, fuse together by age 14-15
-Base of sacrum
-Promontory
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# Promontory? Intervebral disc? Transverse lines? Foramina?
-Tranverse lines (4 of them) from where the individual sacral bones fused
-Promontory is weight supporting. Intervertebral disc sits on top
-Anterior sacral foramina; 4 on left, 4 on right. Nerves exit here
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# Sacral Canal? Foramina? Lateral, medial, median crest, sacral hiatus
| Sacral cornu, Coccyx
-The sacral canal is a continuous opening that was created by the fusion of the vertebral foramen. This is where our spinal nerves and nerve roots sit before exiting the structure
-Posterior sacral foramina; Should be able to access these structures to insert medicine into the sacral canal
-Median sacral crest: Palpable area; remnants of the spinous processes of the origanl sacral vertabra
-Medial sacral crest (R/L): Formed with the fusion of our superior & inferior articular processes
-Lateral sacral crest (R/L): Formed with the fusion of our transverse processes
-Sacral Hiatus: Opening at the base of the sacram. Exit point for our coccyxgeal spinal nerves as well as ligaments that pass through the base of the sacrum (the only way for that to be true is if there is an opening)
-Sacral cornu: Projections that come off the sides of the sacral hiatus
-Coccyx: Originally 4 vertebra, 2-4 fused
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# Line that transects L4? Iliac Spines? Markers for S2 sacral foramina?
-Butterfly pattern
-Iliac crest; most superior ridge. Usually palpable
-If you draw a horizontal line between the two iliac crests, that line should run through the middle of the vertebral body for L4
-Just below that line, in the L4/L5 interspace
-Just above that line, in the L3/L4 interspace
-This line is used ALOT as a marker for epidurals. This line should transect the middle of L4
-Posterior superior iliac spines: Typically able to view if someone is wearing low rise jeans or a bathing suit. These are markers for the posterior S2 sacral foramina. Move down 1cm, move 1cm midline gives you a pretty good approach
The S1 posterior sacral foramina is much more difficult to approach from a perpindicular needle standpoint
-Posterior inferior iliac spine: Much harder to palpate
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# Promontory? Superior articular process? Pubic tubercle
-Anterior superior iliac spine: Inguinal ligament attaches here
-Anterior inferior iliac spine
-Anterior medial pelvis- there are two nubs called the pubic turbercle. The inguinal ligament attaches here
Inguinal ligament: Should be able to palpate or see even in patients with a high BMI. "There's usually a fold or.. well, you guys will figure it out"
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# Anterior longitduinal, inguinal, iliolumbar ligaments, pubic symphosis
-Anterior longitudinal ligament: Continuous with the entire spine
-Inguinal ligament
-Iliolumbar ligament: Connects the transverse processes of L4/L5 with the posterior area of the pelvis
-Pubic symphosis: Connects the two sides of the pelvis
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# Supraspinous Ligament
-Lays on top of the spinous processes down the entire spine, over the median crest of the sacrum
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-Transumbilical plane: Not a great marker because everyone has extra weight here. Located between the L3-L4 disk
-"Two sets of hips"
Superior hips = top of pelvis
Inferior hips = top of femur
-Pubic tubercle could be palpated but not sure what help that would be
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Top of femur= greater trochanter
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-Intervertral discs in between each vertabra. Can degrade overtime
-Anulus Fibrosus: Majority of the intervertebral disc
-Nucleus pulposus: Gel center
-Hyaline cartiledge: At the top and bottom of each vertebral body
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# What's unique here? What surgical procedure can be viewed from this?
-The anulus fibrosus lays in a criss-crossing pasttern along the anterior portion of the vertebral body. This provides a lot of strength
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Anulus fibrosus does not criss-cross on the posterior side of the vertebral bodies, more prone to injuries back here due to trauma or bad genetics
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# Types of surgerys to fix this?
-Posterolateral herniation
-Nucleus pulposus is pushed out of the vertebral disc, puts pressure on the spinal nerve. There is not enough space to accomodate the nucleus pulposus; extremely painful
Herniated disc surgeries:
Disectomy- Remove the part of the disc that's causing the problem. Incredibly painful when people wake up from surgery
Fusion- Stabilize the spine. Anterior approach. Really invasive and causes destabilization of the vertebra above and below the fused bone
Laminectomy- Shave part or remove all of the lamina. Creates more space if successful
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# Where does the CSF go? Connective tissue layers? Subdural space?
Connective tissue layers:
1. Pia Mater: Thinnest layer. Sits immediately on top of the spinal cord neurons and glial cells
2. Arachnoid Mater: Superficial to Pia and the large vessels that perfuse the spinal cord. CSF is subarachoid
3. Dura layer: Outer most layer. Thick and leathery
Subdural space in the spinal cord is a POTENTIAL space. Nothing exists in thts space in the spinal cord
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# Epidural space? Anesthesia? Subarachnoid space?
**Epidural Space: **Immediately outside of the dura. Contains a lot of fat cells & venous blood vessels here. If someone is getting work done on their knee and don't want general anesthesia, and epidural may be a good option. If the drug is fat-based, it will be absorbed into the adipose tissuse of the epidural space. Meaning it will take longer for the drug to take action, and will take longer for the drug to wear off.
Subarachnoid space: CSF, arteries, blood vessels
Spinal anesthesia needs to be done in the lower back once the spinal cord ends. Inserting a needle into the spinal cord accidentally would be pretty terrible
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The spinal cord extends from the medulla to L1. The tip of the cord is the conus medularis, which should terminate at the level of L1.
Spinal nerves extend farther than the conus medularis and then exit wherever they need to
Cervical enlargment: Because we have so many sensory/motor function nerves that control our upperlimbs, we have a cervical enlargment at the levels of C3-C6. This enlargment is immediately above and below where all of these extra neurons are housed.
Lumbar Enlargment: Due to innervation of the lower limbs. T11-L1
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# Brachial & lumbar plexus? Connective tissue layers?
-Cervical enlargment: The nerves that come off of the cervical enlargement feed into the brachial plexus (a giant tangled ball of nerves that we'll learn about in the summer)
-Lumbar enlargement: Nerves coming off of the lumbar enlargement feed into the sciatic nerve and the lumbar plexus
-Dura layer is continuous with the nerve roots all the way to the sacrum. When the nerves exit the spine, that is when the dura layer stops
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# Cauda Equina? Spinal Anesthesia? Filum terminale internum & externum
| Sacral Hiatus?
**-The cauda equina** (typically L1-S5 nerve roots): begins distal to the conus medularis. Specifically, this is a collection of posterior and anterior spinal roots. They come together to form a spinal nerve; however, in the cauda equina, the anterior & posterior roots have not combined into spinal nerves yet. This is a good place for spinal anesthesia
-**Filum terminale: **Connective tissue that is an extension of the pia matter that either comes off of the base of the spinal cord or the base of the dural sac to ensure the spinal cord stays in its natural position.
FT internum: Found within the lumbar cistern. Connects end of cord with end of dural sac
FT externurm: Starts where the lumbar cistern ends. Anchors the spinal cord to the coccyx.
The bones in the spine tend to grow faster that the spinal cord lengthens as we become adults. The filum terminale ligament keeps the cord from retracting upward (really bad)
**-Dural Sac (Lumbar Cistern): **The sac that extends further down the spine than the spinal cord. It is filled with CSF. This allows CSF to circulate much lower than the cord extends. It terminates where the cauda equina becomes spinal nerves that exit the lower parts of the spine (around S2). This is an ideal place for spinal anesthesia
-Sacral hiatus is also a place where spinal anesthesia can be administered
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# Conus medularis? Cauda Equina? Filum Terminale internum?
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# Where does the cord end in adult vs newborn?
Adult- L1
Newborn- L3
Our bones grow faster than the cord lengthens. The end of the cord shifts upward a couple of levels as we mature
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CSF shows up as black space on imaging
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# Lumbar cistern? CSF flow here? Intervertebral discs? CSF sampling?
-Remnants of vertebral disc below S1. These degrade overtime
-The CSF in the lumbar cisten becomes "stale." Does not get refreshed often. This can be a good place to sample CSF; however, this sample will be ~2 day old CSF. Need to take the results with a grain of salt
-Using the posterior superior iliac spine, we can determine where L4 is. Above that, L3/L4 interspace. Below that, L4/L5 interspace. Both are good locations to sample CSF
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1. Showing an epidural approach with the needle. Will not puncture CSF system
2. Spinal anesthesia approach. Quicker, but more dangerous
3. Sacral hiatus
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# What is preventing the midline approach?
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# Whats underneath the arachnoid layer?
Dural layer is thick and leathery
Arachnoid layer deep to the dura. Strong, but much thinner than the dura
Large blood vessels are located under the arachnoid layer
Having the grey matter on the outside perimeter of the brain means that it is more easily perfused
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# Structures? Epidural hematoma? Subdural hemorrhage? Subarach hemorrhage?
-Pia mater sits directly on top of neurons and glial cells.
-In between the pia and arachnoid layer, we have supportive structures called arachnoid trabeculae. These structures give us enough room to house our CSF and blood vessels in the subarachnoid space
-A subarachnoid hemorrhage is usually an arterial bleed. The veins in the subarachnoid space don't get distorted (aneurysm) or ripped very often
-Dura is very thick
-The epidural space is in close proximity to the skull which contains large arteries and veins lined through the skull. Skull fractures typically result in an arterial bleed in the epidural space
-Subdural hemorrhages are usually venous. This is because the dura layer is continuous some of the venous sinuses surrounding the brain
Arterial bleed progresses faster than venous
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# Electrolytes, glucose, pH. Astrocytes role
CSF Composition
| Color? Why is glucose lower?
-Very tight controls on the fluid surrounding our CNS. We have a fairly consisten environment
-Astrocytes help provide this consisten environment. They can absorb or donate electrolytes to maintain normality. (mostly K+)
CSF pH: 7.34
-HCO3- levels in the CSF are slightly lower than in the plasma
Na+: 140mOsm/L
Cl-: Higher than plasma. Usually the same as Na+ in CSF
K+: ~40% less than in the plasma
Mg++: Higher in CSF
Glucose: 60mg/dL
-AVG BG is 90mg/dL in plasma. Glucose crosses the BBB via glut-1 transporters/facilitated diffusion and is constantly being consumed by the CSF (this is why our glucose lvls are lower in CSF). Neurons cannot store their own glycogen or glucose
-CSF should be clear, no large amounts of protein, and no RBCs. May have immune system antibodies
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How does CSF composition limit neurological activity?
-Many neurons are permeable to Cl- due to GABA receptors. Cl- hyperpolarizes the neuron (gaba is the brakes of the CNS)
-Lower K+ hyperpolarizes the cell
-Higher Mg++ (remember, acts similar to Ca++) stabilizes/ calms the cell membrane
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CSF Volume
~150ml in the CNS at all times.
Produced at a rate of 500ml/day, meaning it is replaced about three times per day (except lumbar cistern)
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# How do anesthestics affect this?
How is CSF produced? Where is it produced?
-Produced by epindymal cells.
-Epindymal cells separate the CV system from the CSF circulatory system. These cells have access to blood for water, sodium, chloride.. etc
-These cells have Na+ and Cl- leak channels, allowing Na+ and Cl- to move into the cell from the blood. Water follows.
-Na+ ATPase pump cycles and actively pushes Na+ out into the CSF circulation, Cl- and water passively follow
-There are some anesthestics that can speed up or decrease the function of the Na+ ATPase pumping, meaning they can speed up or slow down CSF production
-A large collection of epindymal cells are called the choroid plexus. There is one in each ventricle
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# Ventricles & their locations, arachnoid gran. function?
| What is the name of the container that the median aperture feeds?
-CSF is produced in the choroid plexus (four of them)
-3rd ventricle, 4th ventricle, lateral ventricles
-3rd ventricle is located in the diencephalon where the hypothalmus is
-4th ventricle is located in the middle of the brain stem, just anterior to the cerebellum
-Left & Right lateral ventricles are deep within the cerebral hemispheres
-Cerebellomedulary cistern (cisterna magna)
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# Which ventricle? CSF pathways
Flows from the lateral ventricles through the interventricular foramen (Foramen of Monroe) to the 3rd ventricle
3rd ventricle through the cerebral aquaduct (Aquaduct of Sylvius) into the 4th ventricle
Three exit points from the 4th ventricle:
1. Central canal into the spinal cord
2. Lateral apertures, L & R, (Foramen of Luschka) provide a conduit for the CSF to exit the lateral sides of the 4th ventricle
3. Median aperture (Foramen of Magendie) empities into the cisterna magna to allow for CSF to circulate around the cerebellum
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Hydrocephalus
Extra CSF circulating in the CSF circulatory system
Communicating hydrocephalus: Pathways are intact, but CSF isn't being absorbed, or removed, from the CSF circulatory system like it should be. Ventricles are not enlarged, ICP is just higher Ex: blocked arachnoid granulations.
Noncommunicating hydrocephalus: When one of our drainage pathways is blocked (usually the cerebral aquaduct, tumor or something else). CSF is still being produced at a constant rate, ventricles will enlarge and compress the neurons and glial cells
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Arachnoid Granulations
-"In-foldings" located on top of the brain just superior to the longitudinal fissure (midline along the brain)
-Pressure blow-off valves that mediate CSF being absorbed back into the CV circulatory system
-Normal ICP is 10mmHg. If ICP increases to 12, CSF should be pushed out of these arachnoid granulations
-Majority of absorption happens here and typically happens at the same rate CSF is being produced. Some happens at the base of the spinal cord
-What happens if someone has a stroke and blood is clotted over the arachnoid granulations? Communicating hydrocephalus
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Sinus in this context = big vein with structure to it. Venous collecting systems that perfuses the brain and cord
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# 1-7, 10, 11
1. Superior sagittal sinus
2. Inferior sagittal sinus
3. Straight sinus- Extension of the inferior sagital sinus, Connects the superior and inferior sinuses. Where these meet, the vessel "straightens"
4. Sinus confluence- Where the superior, inferior, straight, and transverse sinuses meet
5. Transverse sinus (L & R)- Lateral exit point for superior & inferior sagittal sinuses
6. Sigmoid sinus (hair pin turn): Descends down via the internal jugular
7. Cavernous Sinus: Venous collection pool for the face and the front of the brain. Located anterior & medial
10. Falx cerebri: Connective tissue that separates the left and right cerebral hemispheres.
11. Tentorium Cerebeli: Where the falx cerebri forms a floor for the occipital lobe of the brain to sit on. The cerebellum will be located underneath
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# How does the CSF enter the cardiovascular system?
The arachnoid granulations sit superior to the superior sagittal sinus. CSF leaves via the arachnoid granulations, and enters the cardiovascular system through the super sagital sinus
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# Blood flow through this image?
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# Venous drainage flow?
-All cranial blood is emptied into the internal jugular vein.
-Superficial structures on the side of the end will empty into the external branch of the jugular vein
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# Arteries providing blood flow? Arterial blow flow speed
| Amount of BF to grey matter, white matter
Two vertebral arteries-Run along the back of the neck and feed the posterior portions of the brain
Two internal carotid arteries- Feed the more anterior portions of the brain
The internal carotid arteries are a protected part of the circulation that are going to ensure that we have a very large amount of blood flowing to the brain relative to it's size (under normal circumstances)
External carotid arteries- Supply blood to external, superficial structures
-Arterial BF to the brain is 750ml/min. That's 15% of our CO (5L/min)
-50ml/min/100g of tissue
-80% of brain BF is routed to the grey matter-This is where decisions are made, electrolyte levels in the cell are managed
-20% to the white matter (remember, white matter is really efficient)
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Cranial Sinuses
| What are they made of?
The walls of the cranial sinuses are formed from the dura mater and fairly stiff and rigid.
The reason we have a venous hemorrhage with a subdural bleed is because one the walls of these large veins are basically continuous with the dura mater
-The cranial sinuses are well supported with connective tissue layers compared to veins in the rest of our body (flimsy, collapsable)
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# Circle of Willis & Connecting arteries
| Cerebellar arteries
**-Circle of Willis:** Continuous pathway of arteries that will increase the likelihood of developing collateral blood flow if necessary
-Begins with the **internal carotid arteries** --> turn into **middle cerebral artery** once they enter the Circle of Willis. MCA is the largest and perfuses the lateral portions of the brain. This is probably the worst place to have a stroke
-**Vertebral arteries** feed in through the posterior portion of the brain --> form the **basilar artery** just inferior to the pons
-**Posterior cerebral artery **-->
-Early/Precommunicating part (P1); Part of the Circle of Wilis
-Late/Postcomminucating part (P2); extends from Circle of Willis . Perfuse the posterior part of the brain as well as far lateral portions
** Posterior communicating artery** connects both posterior cerebral arteries to the middle cerebral artery
-**Anterior cerebral artery**-->
-Early/Precommunicating part (A1); Part of the Circle of Willis
-Late/postcommunicating part (A2); Extend from the Circle of Willis. Perfuse the anterior portion of the brain, stopping around midline
**Anterior communicating artery** connects both anterior cerebral arteries in the circle of willis. Very small
-If it's part of the Circle of Willis and it's connecting large vessels to each other, it's called a communicating artery. If it's projecting from the Circle of Willis, it's called a post-communicating artery
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# Which artery perfuses each area?
-Pink areas are perfused by the anterior cerebral artery
-Green area is perfused by the MCA
-Blue areas are perfused by the posterior cerebral artery
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# Identify arteries in the Circle of Willis
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# Cerebellar Blood Flow
-Lateral view of cerebellum and brain stem
-Cerebellum helps us coordinate complex motor movements
* Superior Cerebellar Artery; Perfuses the superior portion of the cerebellum. Branches off the basilar artery
* Anterior-Inferior Cerebellar Artery; Perfuses the middle of the cerebellum. Branches off the basilar artery
* Posterior-Inferior Cerebellar Artery; Perfuses the inferior portion of the cerebellum. Arises from the vertebral artery
All arteries have L/R branches
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Associated with skull fractures. Usually trauma
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# What makes up the walls of the sinuses?
-Dura is the yellow structure. We can see that the dura extends into the walls of the cranial sinuses
-This results from tearing of the wall of the dura
-We would see this happen in a car accident, terrible whiplash, and don't start to get a headache until a few days later
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Arterial bleed. This injury is messy, not contained in one spot. The blood here infiltrates the neurons and the glial cells
-Aneurysms are the result of genetics or lifestyle habits.
If you've been an alcoholic fro 30+ years, the blood vessels tend to become very thin. They don't handle abuse well
-HTN for prolonged periods of time can produce an aneurysm
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# What influences it?
Brain Blood Flow
-Determined by the metabolic requirements of the tissue
-CO2 is the major byproduct of metabolism in the brain. The more CO2 being produced, the more brain blood flow we're going to have. CO2 moves into the blood vessels surrounding the brain, and those vessels vasodilate in order to increase BBF
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# LLA & ULA? Relationship with drugs and autoregulation
Autoregulation of BBF
-A system that is able to maintain nearly constant BBF under changing environmental conditions
-Systemic blood pressure drives blood flow
-Autoregulation occurs between 50mmHg and 150mmHg, if we're outside of these limits, we should see a linear drop or increase based on what our map is
-Lower limit of autoregulation (LLA); 50mmHg
-Upper limit of autoregulation (ULA); 150mmHg
-If our cerebral metabolism hasn't changed, but our driving pressure increases, then the vessels in the brain will constrict to ensure we are not receiving too much BBF
-If we have no autoregulation and we have an increase or decrease in BP, we will see a linear response in the relationship between BBF and pressure
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# What happens w/ prolonged HTN? How is vascular health determined?
Adaptation of Autoregulation of BBF
-Chronic HTN causes the system to adapt to those conditions. Our autoregulation curve will shift to the right to the "new normal" changing both our LLA and ULA
-Blood vessels are able to squeeze tighter, they become harder and thick (arterial sclerosis). They're able to withstand higher pressures; however they are more sensitive to lower pressures because these vessels can only relax so much.
-Vascular health is determined by the ability to squeeze and relax. If the blood vessels in the cardiovascular system cannot squeeze and dilate, then the injury (stroke, MI) will be significantly worse
-Collateral circulation in the circle of willis is affected by arterial sclerosis
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Drugs and Autoregulation of BBF
-Pretty much all volatile anesthestics will limit the ability of the blood vessels to autoregulate
-This may interfere a little (small slant on the graph) or it could take your autoregulation offline completely (line is extremely steep)
-How is this determined? There are "error bars" on the graph, but because there is so much variability when collecting data with living beings, the larger the error bars are. There are limitations with how these experiments are run. The data may show that the effect of a volatile anesthetic on cerebral BF is not statistically signifcant, but that does not mean it does not have any affect on autoregulation
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# Motor Neuron Overview & How do we get there?
Release of ACh at the NMJ (Presynaptic)
-Cell body of the motor neuron is located within the spinal cord (anterior horn)
-Cell body fires an action potential, which moves down the motor neuron via fast Na+ channels. This Na+ causes VG Na+ channels to open. The cell repolarizes via K+ channels. Na+, K+, ATPase pumps exist here as well
-The action potential also opens P-Type Ca++ VG-Ion Channels--> Ca++ comes flooding into the end of the motor neuron. Ca++ entry into the motor neuron is the stimulus for the neuron to release ACh. This Ca++ acts on storage vesicles (Vp-2, Vp-1).
Vp-2 storage vesicles are sitting by the cell wall and are ready to fuse with the cell wall to empty their contents into the synapse. Ca++ comes into the cell and causes the vesicles to fuse to the cell wall--> empty ACh into the synpase
Vp-1 storage vesicles are not quite ready to release ACh. They are not close enough to the cell wall or not completely filled with ACh. We have more of these than Vp-2
-Ca++ transport pump (ATP dependent) moves Ca++ out of the cell, stops the Vp-2 vesicles from fusing with the cell wall and releasing ACh
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# What happens here? End plate potential? Total amt nACh-r?
Release of ACh- Postsynaptic
| Why do we always have sufficient end plate potential? Next step?
-There are two binding sites on the nACh-R. Both must be bound simultaneuously for the channel to open up. Once bound, Na+ floodsinto the cell. Sometimes Ca++ sneaks in. K+ tries to sneak out, but gets knocked out of the way
-These nACh-R are in very close proximity to the motor neuron and in very high density (millions)
-The localized depolarization that is happening here at the NMJ due to the nACh-r opening is called the **end plate potential.** This is the initial stimulus
-An end plate potential, in the healthy muscle, will always give rise to an action potential. The action potential is mediated through fast Na+ channels along the muscle. This provides the current for an action potential down the length of the skeletal muscle
The reason we always have a sufficient end plate potential to generate an action potential is that we have significantly more receptors and neurotransmitters than we actually need
We need roughly 500,000 nACh-r activated to give us an action potential which is 10% of the amount of nACh-r that we have available (5 million). Need 1million ACh to bind to receptors. ~ 2million are released
Next step would be contraction of the muscle
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# Innervated by? Where are the Neuron Cell bodies?
Skeletal Muscle
| What is the reflex arc?
-Every skeletal muscle fiber has one motor neuron associated with it
-Some are innervated by multiple motor neurons (ex: ocular muscles of the eye sockets)
-Motor neuron cell bodies are located in the anterior horn
-Cell bodies can be excited by descending pathways (motor pathway)
-Can also be excited be the reflex arc; Ex: A very strong pain signal can elicit a response- withdraw from the pain. This happens at the level of the spinal cord
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# Actin/Myosin, SR, Ca++ storage, T-Tubules
Skeletal Muscle Cell Anatomy
-Actin/Myosin: Contractile elements within the muscle cell. Arrange in tube like structures
-Sarcoplasmic Reticulum: Specialized endoplasmic reticulum in the muscle cell. This is where Ca++ is stored for contraction. Skeletal muscles are not really dependent on Ca++ coming in from outside the cell
Action potential starts at the NMJ and spreads lengthwise down the skeletal muscle. Because the skeletal muscles are so large, they have a specialized structure that allows the action potential to spread horizontally through the muscle
-Tranverse tubules (T-Tubules): Specialized structures that allow the action potential to spread perpindicularly through the muscle that allows the action potential to spread throughout the entire muscle
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# Mitochondria (What do they produce?) Clefts? Myelin?
Skeletal Muscle- NMJ Anatomy
| Phosphatidylcholine?
-Lots of mitochondria located here and in the presynaptic motor neuron. They produce Acetyl
-Choline is stored in the cell wall via phosphatidylcholine
-"Infoldings" at the NMJ on the skeletal muscle are referred to as primary or secondary clefts.
-nACh-r located at the begining of the cleft, closer to the neuron
-The schwann cell is located at the distal end of the motor neuron, and the motor neuron is wrapped in myelin
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Acetylcholinesterase
-Breaks down ACh
-Achesterase is expressed in the skeletal muscle and is "parked" at the NMJ. This limits the length of depolarization. This gives the sequence of events in an actional potential a finite timeline. Needed to reset
-Uses hydrolisis to break ACh down into acetyl (acetic acid, acetate) and choline.
-Acetate is a small starch group
-Choline is put back into the motor neuron two ways 1) ATPase Choline pump and 2) a Na+, Choline transporter (2ndary active transport)
Acetate is recycled for re-use (not as well understood)
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Skeletal Muscle Ca++ Signaling (Action Potential)
-Action potential is generated in the skeletal muscle cell from the motor neuron and mediated by fast Na++ channels and repolarized with slow K+ channels
-Action potential sweeps through the muscle cell and down the t-tubule.
-DHP voltage sensors (located in the cell wall & t-tubule) "sense" the action potential. The DHP voltage sensor has a physical attached to the Ca++ release channel in the SR and tugs it open, releasing the Ca++ (like a cork).
-Very minimal amount of Ca++ comes in from outside the cell. The vast majority of the Ca+ is stored in the SR
Ryanodine Receptor and Ca++ release channel are the same thing. They are not true receptors, but what they do is facilitate release of Ca++ from the SR via a physical attachment to the DHP sensor
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Skeletal Muscle Ca++ Signaling (Repolarization)
-SERCA Pump. Sarco Endoplasmic Reticulum Ca++ ATPase pump
-Once the action potential is over (contraction happens) the SERCA pump uses ATP to push Ca++ back into the SR
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# Step by step
Skeletal Muscle E-C Coupling
1. Motor neuron generates an action potential (stimulus from brain or reflex arc). A.P spreads along the neuron to the most distal end
2. Activates P-Type Ca++ channels. Ca++ Influx into the motor neuron
3. VP-2 vessicles fuse to presynaptic cell wall
4. ACh secreted by presynaptic neuron into the NMJ
5. ACh binds with nACh-r
6. Na+ influx into the skeletal muscle cell along with some Ca++
7. Na+ & Ca++ influx generates LOCAL action potential--> end plate potential
8. EPP always causes an action potential in the skeletal muscle
9. A.P spreads down the muscle fibers in both directions
10. DHP voltage sensors sense AP, pull on ryanodine receptors (Ca++ release channel)
11. Ca++ influx into the sarcoplasm from SR
12. SERCA pump pumps Ca++ back into SR --> muscle stops contracting
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Na+, K+, ATPase, Leak Channel Quick Overview
-Na+ and K+ leak channels are on every cell wall, never close. Na+ leaks in, K+ leaks out
-K+ typically only leaks out of the cell while the cell is very positive
-Na, K+, ATPase pump pumps (3) Na+ back out, 2 K+ back in against their concentration gradients. This is responsible for the Na+, K+ concentration gradients
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Myastenia Gravis
| Dysfunctional Neuromuscular Physiology
-Immune system dysfunction where we create antibodies against our nACh-r. An immune response to inflammation of a genetic anomaly with the thymus gland
-Antibodies bind to the nACh-r, immune system destroy the receptors over time. (Antibodies cross-react with the nACh-r)
-Immune system infiltration of the NMJ causes scar tissue to form over the primary & secondy clefts --> less surface area for the these receptors to be located in, and less space for fast Na+ channels
-Remove the thymus gland, plasmapherisis to remove circulating antibodies (typically pull off more than that specific antibody)
-Acetylcholinesterase inhibitors (-stigmine) can be useful. Prolong the activity of ACh at the NMJ, has more time to interact with it's receptors
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# LEMS/ELMS
Lambert Eaton Myastenic Syndrome
| Dysfunctional Neuromuscular Physiology
-Perineoplastic syndrome. Can develop if you have cancer (especialy lung cancer). Antibodies are generated towards P-type Ca++ channels
-The most important role for P-type Ca++ Channels is neuromuscular transmission
-Antibodies either obstruct the P-type channel or the immune system destroy them, Ca++ cannot come into the motor neuron, ACh cannot be released
**-This is a motor neuron dependent disease**
-Acetylcholinesterase inhibitors will not help
-Plasmapheresis
-Remove the lung tumor
-Drugs used to tx this are horiffically dangerous
These drugs work by blocking K+ channels (can block leak channels, more specific to VG K+ channels).
-TEA- tetraethyl ammonium
-4-5 Diaminopuridine
How do these work?
Opening K+ channels would increase K+ permeability, causing the cell to be more negative, and hyperpolarizing the cell membrane.
These drugs work by CLOSING the K+ channels. This will cause depolarization (Vrm is more positive), typically resulting in a longer depolarization. With a longer depolarization, we should have more opportunity for Ca++ to come in through the P-type Ca++ channels that are unblocked.
P-type Channels, unlike L-type, do not have an inactivation gate. They open when the cell is depolarized, they close when the cell repolarizes
These would be great if they were specific to motor neurons. They're terribly dangerous because they are cross-reactive at every VG K+ channel that we have (heart)
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Depolaring Muscle Relaxant
-Succhinylcholine is pretty much the only one in use in clinical practice
-Two acetylcholine molecules
-Causes sustained depolarization of the skeletal muscle (at the NMJ, nACh-r are not located anywhere else) because of prolonged opening of the nACh-r. Typically, depolarization will last ~1milisecond or less. Sux causes depolarization to last 10ish minutes
-Acetylcholinesterase is not able to break the ester bond between the two ACh molecules in sux
Muscle depolarizes--> we will see fasciculations or twitch contraction (first thing we see) --> because these receptors are open, Na+ is constantly coming into the cell through nACh-r. Fast Na+ channels cannot reset. Na+ channels will be stuck in an inactive form. The Na+, K+ pumps will have a hard time keeping up with all of the Na+ coming in. The positive charge on the inside of the muscle cell is causing more K+ to leave through the leak channels and the VG channels. Will cause serum K to increase by about 0.5mOsm/L
In a normal, healthy person, not an issue. If someone has abnormal skeletal muscles (stroke, denervation injury) can greatly expand the amount of skeletal muscle that will hemmorhage K+ because these conditions will cause more nACh-r to generate even in areas outside the NMJ
