Neuro Flashcards
Name the physical features of the frontal lobe
Precentral gyrus (primary motor cortex)
Superior frontal gyrus
Middle frontal gyrus
Inferior frontal gyrus
Name the physical features of the parietal lobe
Postcentral gyrus
Supramarginal gyrus
Angular gyrus
Name the physical features of the temporal lobe
Superior temporal gyrus
Middle temporal gyrus
Inferior temporal gyrus
temporal pole
Name the physical features of the occipital lobe
Occipital pole
Preoccipital notch
Name the main features visible on the medial aspect of the brain
Corpus callosum Cingulate gyrus lateral, third ventricles Pons and medulla Thalamus
What is the function of the cingulate gyrus?
Gateway to the frontal cortex, higher functioning, and the flight and fight areas of the brain
Describe the precentral gyrus and its associations
It is the primary motor cortex, and it is arranged in a homuncular fashion. This means that the part for the face is located basally, then eyes, hands, torso, legs etc. It is associated with the motor planning area of the frontal cortex, which includes broca’s area, eye fields and exter’s area.
Describe the rest of the frontal lobe and its overall function
The frontal lobe contains the superior, middle and inferior frontal gyri. Its function is in intelligence, behaviour, personality, mood and cognitive function.
Describe the SMAGLA and the overall function of the parietal lobe
SMAGLA is associated with reading and writing, respectively, and have connections to the eye fields and exter’s area. The parietal lobe is associated with spatial awareness, 3d recognition and abstract awareness on the LHS, and music, non verbal communication and nuance on the RHS.
Describe Wernicke’s area and the primary auditory cortex
Wernicke’s area surrounds the primary auditory cortex on the superior temporal gyrus. The auditory cortex receives input from CNVIII to separate deep vs high sound pitches. Wernicke’s area interprets the sound, and has a connection to broca’s area called the arcuate fasciculus. It also has a connection to the SMG.
Describe the overall structure of the temporal lobe and its function
The temporal lobe has superior, middle and inferior gyri. It is involved in mood, memory, aggression and intelligence.
Describe the different aphasias that can form and how to tell two apart
Connectional aphasia: Understand what is being said and can verbalize, but the response is not appropriate
Sensory aphasia: Lesion in Wernicke’s area. CCannot understand what is being said but can produce words.
Motor aphasia: Can understand what is being said but cannot verbalise
Can tell the difference by asking for a written response to a verbal question
Describe the occipital lobe’s structure
It has the primary visual cortex at the occipital pole, which then dives deep. It also has a secondary cortex surrounding it and dipping into the temporal lobe, which is used to interpret the raw info given by the primary
What is the difference ebtween allocortex and neocortex?
Most of the brain’s cortex is neocortex, which is made of 6 distinct cell layers
Allocortex has 3 layers of mixed cell type, and only covers a very small portion of the inferior brain. It is associated with fight or flight, the hippocampus and the olfactory centre
What are the 6 layers of the cerebral cortex and what is its general pattern?
I: Molecular II: External granular III: External pyramidal IV: Internal granular V: Internal pyramidal VI: Multiform The upper 3 layers are involved in information from brain to the brain The lower 3 layers are involved in relaying information between the brain and spinal cord
Describe the molecular layer of the cerebral cortex
Nonspecific cells. Important for development as it’s where radial fibres stick into the neocortex and allow its integration into the brain
Describe the external granular layer of the brain
Made of small granular neurons, which receive sensory input from other brain areas (eg. ears)
Describe the external pyramidal layer of the brain
Cells taking info to other cortex areas. They only carry information a short distance and so are small cells (10-40um)
Describe the internal granular layer of the cortex
Granular cells that receive sensory input from the periphery
Describe the internal pyramidal level of the cortex
Betz cells. Large motor neurons of the pyramidal tract (UMNs). 60-120um.
Describe the multiform layer of the cortex
Integrate different sensory inputs of the brain
What can afferent and efferent fibres also be called when in the brain?
- Efferents can also be called corticofugal.
- Afferents can also be called Corticopetal
What are the major forms of arrangement of these six layers, and where are they likely to be found?
It can be homotypical- around equal amounts of each cell type. Found where many types of info are received and sent. Eg. Prefrontal cortex, parietal cortex, temporal cortex
Heterotypical is divided into two categories
Agranular hetero typical is when there are more pyramidal cell types as their primary function is projection to other areas or to the spinal cord. Areas III and V are increased, while II and IV decrease. Eg. Primary motor cortex
Granular heterotypical is where there are more granule cells as the primary function is reception of info. II increases, IV increases massively, and III and V decrease. Eg. Primary somatosensory, visual or auditory cortices.
Describe the circle of willis
Posterior cerebral arteries join the middle cerebral arteries via the posterior communicating arteries. The middle cerebral arteries (arising from internal carotids) join to the anterior cerebral arteries via anterior communicating arteries
Describe the circulation of the posterior brain
2 vertebral arteries join to form the basilar, which then give anterior cerebellar, superior cerebellar, pontine and posterior cerebral arteries
Describe the structure and associated function of the internal capsule
The anterior internal capsule takes info to the frontal lobe from the thalamus (eg. memory)
The curve in the internal capsule is called the genu. It separates the lens and the caudate nucleus
The outer posterior IC takes motor information from the primary motor cortex to the spinal cord
The inner posterior IC takes sensory info from the spinal cord to the primary sensory cortex.
These two areas are arranged in a homuncular fashion, with the genu representing the face, and the rest of the body located more posteriorly
What does each thalamic nucleus do?
The ventroposterior nucleus is responsible for receiving sensory information and sending it out to the primary sensory cortex. The medial part represents the face and the lateral represents the body.
The VAVL nuclei receives info from the basal ganglia and sends it to the motor planning area
The Anterior nuclear group allows memories to be retrieved from and sent to the frontal cortex via papez’s circuit.
The medial and lateral groups integrate sensory input from the association cortices, with the lateral being particularly involved in secondary visual information.
The lateral geniculate body receives visual information from the eyes and sends it to the primary visual cortex
The medial geniculate body receives auditory information from the ears and sends it to the primary auditory cortex.
The Intralaminar nuclear group is responsible for consciousness.
What are the overall functions of the thalamus?
Monitors and gatekeeps info for higher cortex
Consciousness
Integrating regionalized brain function
Motor planning and refining
Describe the reticular sheet
A membrane beneath the thalamus which controls UMN sensitivity
Describe papez’s circuit
Info is sent in a circle from the anterior thalamic nuclei, to the cingulate gyrus, to the parrahippocampal gyrus, to the hippocampus, to the fornix, to the mamillary body, and back to the anterior thalamic nuclei.
The cingulate gyrus also communicates with the frontal cortex.
Describe the basic shape and ending of the spinal cord
There are two enlargements- the cervical and lumbar.
The cord terminates at the bottom of L1, and forms the cauda equina. The filum terminale of this is attached to the base of the coccyx.
The arachnoid mater terminates at S2 level, and the dura mater ends at S3.
What are rexed’s laminae?
10 subdivisions of the gray matter of the spinal cord 1. Posteromarginal nucleus 2. Sustantia gelatinosa 3-4. Nucleus proprius 5-6 7. Intermediate zone 8-9. Medial and lateral motor columns 10
Describe the functions of the different parts of the gray matter of the spinal cord in terms of non discriminative sensation
The posteromarginal nucleus and substantia gelatinosa perform the same function in pain and temperature sensation, although the SG has opioid receptors, so pain referred here can be lessened with analgesics. A further neuron carries the information either to area 8/9, which has LMNs necessary for creating a polysynaptic reflex, or decussates at the anterior white commissure, to be transferred to the brain via the lateral spinothalamic tract.
Describe the functions of the different parts of the gray matter of the spinal cord in terms of discriminative sensation
The nerve fiber enters either directly to the gracile/cuneate fasciculi (25%) or else enter areas 3/4 or the dorsal nucleus of clark. These then conglomerate to form another neuron stretching from the gray matter into the dorsal funiculus, which prevents increasing spinal cord size superiorly.
Alternately, the fiber could go into area 8/9 to provide a myotactic reflex (although this is slow due to unmyelinated fibers)
Describe the functions of areas 5-7 of the gray matter
5-6: Abdominal and internal organs’ sympathetic supply
7: Intermediate zone for sympathetic input.
Describe where sensory vs motor neurons are located in the thalamus, cortex and spinal cord
Sensory fibers are located posteriorly, motor are anterior
Describe the function of the gray matter in terms of motor input
UMNs descend via the motor columns, allowing motor info to travel down to the spinal cord. These move into areas 8/9, where they synapse with LMNs and exit via the ventral root
Describe the organization of the midbrain
Most anterior is the crux cerebri, which transmit motor info from the primary motor cortex to the spinal cord, helping to start off the corticospinal pathway. It is arranged in a homuncular fashion, with face medial and body lateral for each of the legs.
Posterior to this is the substantia nigra, which produces dopamine
Deep to this is the tegmentum, which also extends through the brainstem. It is here called the midbrain tegmentum, and receives sensory info from the spinal cord, sending it to the brain.
Most posteriorly are the superior (sight reflex) and inferior (sound reflex) colliculi, made of 4 nerve fibers. Collectively they are called the tectum or corpora quadrigemina
Describe the arrangement of the pons part of the brainstem
Most anterior is the pons, which is overlaid by the basilar artery
It contains the pontine nuclei, which form a conduit from the cortex to the cranial nerve nuclei via the brainstem. This then transmits motor info to the face.
This overlays the pontine tegmentum, then the fourth ventricle, and most posteriorly is the cerebellar peducle, which transmits info to and from the cerebellum
Describe the arrangement of the medulla part of the brainstem
Most anteriorly is the medullary pyraminds, which are where motor info decussates
This overlays the medullary tegmentum, where the gracile and cuneate nuclei are found, and also contains the inferior olives, which coordinate exchange of info between the spinal cord and cerebellum
Describe the corticospinal pathway
It begins in the primary motor cortex before descending through the crus cerebri in the midbrain, into the pons, and then 85% cross over in the medullary pyramids. It then forms the lateral corticospinal tract, which descends into area 8/9 of the gray matter before exiting the ventral root. 15% descends straight down, and crosses over the anterior white commissure. It is thought that these are axial muscle fibers
Describe the corticobulbar tract
It begins in the primary motor cortex before descending through the crus cerebri in the midbrain. Once it enters the pons it synapses with the nucleus of the cranial nerve it supplies, which then runs out of the pons to the face
Describe the dorsal column- medial lemniscus pathway
It enters the spinal cord through the dorsal root ganglion, before entering the gracile/cuneate fasciculi. Then it runs up the dorsal funiculus before synapsing at the gracile/cuneate nuclei. They decussate as internal arcuate fibers, and run up the medial meniscus pathway. They enter the thalamus at the VP nucleus, and then run through the internal capsule to the homuncular part of the primary somatosensory cortex
Describe the lateral spinothalamic tract
Enters the dorsal root ganglion, into regions 1/2 of the gray matter. It then synapses, and decussates at the anterior white commissure. It ascends in the lateral spinothalamic tract, where it then joins the medial lemniscus pathway and enters the VP nucleus of the thalamus. From there it runs in the internal capsule to the homuncular part of the primary somatosensory cortex.
What is the mnemonic used to remember the functions of each of the cranial nerves?
Some Say Marry Money But My Brother Says Big Brains Matter More
What are the 12 cranial nerves?
1: Olfactory
2: Optic
3: Optothalamic
4: Trochlear
5: Trigeminal
6: Abducens
7: Facial
8: Vestibulocochlear
9: Glossopharyngeal
10: Vagus
11: Accessory
12: Hypoglossal
Where do each of the nerves exit the brain?
Cribiform Plate: I Optic Canal: II Superior Orbital Fissure: III, IV, V1, VI Foramen Rotundum: V2 Foramen Ovale: V3 Internal Accoustic Meatus: VII, VIII Jugular Foramen: IX, X, XI Hypoglossal Canal: XII
What is the function of the Olfactory nerve and what can happen if it goes wrong?
- Smell
- Fright and flight response
as only input into the limbic
system e.g. smell burning –>
Run fast - Issue can cause loss of smell sensation
What is the function of the optic nerve and what can happen if it goes wrong?
- Transmits visual information
- There is a chiasma where the medial fibers of each nerve decussate. If there is a lesion before the chiasma, there will be full blindness in one eye
If there is a lesion post chiasma, there will be partial blindness
What is the function of the oculomotor nerve and what can happen if it goes wrong?
Innervates ciliary muscle, sphincter of pupil and all external eye muscles except superior oblique muscle and lateral rectus muscle Muscles: Superior rectus, medial rectus, inferior rectus, inferior oblique - Damage --> Loss of light reflex, dilated pupil (Decreased tone of the constrictor pupillae muscle), downward, abducted eye on the affected side due to the unopposed action of the superior oblique and lateral rectus muscle
What is the function of the trochlear nerve and what happens if it goes wrong?
“Innervates superior oblique muscle (pulley) - pulls eye
up and outwards”
Trochlear nerve palsy - downward, inwards gaze
What is the function of the trigeminal nerve and what happens if it goes wrong?
Takes info about sensation back to the brain. It innervates skin as well as internal mucoase.
- V1 = Carries info from Opthalmic division
- V2 = Carries info from maxillary division
- V3 = carries info fromMandibular division.
ALSO HAS MOTOR FUNC. innervates chewing muscles. Innervates some salivary glands
- Trigeminal neuralgia = sudden
attacks of pain which are
triggered by touching the face,
chewing, speaking or brushing
teeth.
What is the function of the abducens nerve and what happens if it goes wrong?
"Innervates lateral rectus muscle (involved in lateral gaze - used in visual tracking or fixation on an object)" - Abducens nerve palsy --> The affected eye turns in towards the nose and is unable to abduct properly (double vision)
What is the function of the facial nerve and what happens if it goes wrong?
- Motor = Muscles of facial expression - Parasympathetic = submandibular, sublingual, lacrimal glands - Sensory = anterior 2/3 of tongue, soft palate - Facial nerve palsy - facial paralysis due to a lesion in the facial nerve (symptoms also include dry mouth and altered taste. Called bell's palsy and is due to compression of the nerve through the facial canal.
What is the vestibulocochlear nerve and what happens if it goes wrong?
Transmits sound (Cochlear) and balance (Vestibular) information from inner ear to the brain Damage to nerve - hearing loss, vertigo, false sense of motion, loss of equilibrium, nystagmus, motion sickness, tinnitus
What is the function of the glossopharyngeal nerve and what happens if it goes wrong?
- Sensory = posterior 1/3 of tongue, tonsil, pharynx, middle ear - Motor - stylopharyngeus, upper pharyngeal muscles, parotid gland - Damage to glossopharyngeal nerve = loss of taste (esp bitter & sour flavours), trouble swallowing, absent gag reflex
What is the function of the vagus nerve and what happens if it goes wrong?
- Parasympathetic input to GI system and Heart - Motor = heart, lungs, palate, pharynx, larynx, trachea, bronchi, GI tract - Sensory = heart, lungs, trachea, bronchi, larynx, pharynx, GI tract, external ear - If diabetes has damaged the vagus nerve, it can cause gastroparesis: muscles of the stomach and intestine arent able to efficiently move food through the GI system. Symptoms : nausea, vomiting, heartburn, constipation, abdominal bloat, stomach spasms and decreased appetite
What is the function of the accessory nerve and what happens if it goes wrong?
Innervates: - Stemocleidomastoid (Tilt & rotate head) - Trapezium (elevate shoulders) Accessory nerve disorder - inability to shrug shoulders and rotate head
What is the function of the hypoglossal nerve and what happens if it goes wrong?
Tongue muscles & strap muscles by ansa cervicalis. Also controls hyoid bone alongside some spinal nerves Paralysed tongue, or deviated away from injured side. See problems swallowing, chewing, speaking
Where are the cranial nerve nuclei? (generally)
I & II: Allocortex/Limbus
The rest sit within the midbrain and hindbrain
There can be multiple nerves associated with one nucleus, or one nucleus associated with one nerve
What are the different categories of sensory vs motor nerves?
Sensory can be: - General somatic (skin) - General visceral (organs) - Special somatic (sight, sound, balance) - Special visceral (taste/smell) Motor can be: - General somatic (skeletal) - General visceral (smooth) - Special visceral (pharyngeal arches)
What are the different patterns of sensory loss?
- Localized numbness
- Generalized one sided numbness
- Loss of sensation below a spinal level
- Glove and stocking loss
- Dermatome loss
- Trunk or plexus loss
How do different spinal cord lesions present?
- Can give weakness below a certain sensory level even if no discriminative sensation is lost. This is because a partial lesion can preserve the posterior columns, so pinprick sensation must be tested to determine whether the ventrolateral areas have been compromised
- Can give bilateral signs or paralysis
- Central lesions can also spare the posterior columns and power as they compress the anterior white commissure.
Hemicord lesions cause motor weakness and loss of discriminative sensation on the same side as the lesion, and loss of non discriminatve sensation on the opposite side to the lesion
How do PNS lesions present?
Mononeuropathy can be an AI disease, vasculitis or nerve compression. Sensory loss and weakness in the supplied area
Polyneuropathy presents as motor, sensory or a combination of both. Different issues can affect myelinated or unmyelinated fibers, or even myelin itself.
Eg. Diabetes attacks axons so it starts in the longest (feet) before moving into the hands
Plexus lesions (eg. slipped disc) is a single nerve issue in a dermatome
Guillain Barré syndrome is an example of a demyelinating disease
How do UMN vs LMN symptoms present?
UMN issues show weakness, increased tone and reflexes. Half body or spinal level may be affected
LMN issues show weakness, decreased tone and reflexes. They are due to nerve root or peripheral distal issues
What is the best way to do a sensory exam?
Keep questions unslanted, ie. does this feel the same as this?
Do it at the end of an interview to confirm a hypothesis, rather than to generate one
What are some common sensory exams and how do you do them?
Light touch: Dab a cotton wisp onto the skin, looking for lack of perception, no difference in perception, or different quality of perception (ie felt as pain)
Pinprick: Lightly touch the sharp end to the skin, but not hard enough to puncture. Can also use to differentiate sharp vs. dull
Joint position: Stabilize the joint with hand and then move it while the patient’s eyes are closed, asking them to tell you in which direction it’s being moved
Vibration: Press a tuning fork to the pulp of middle finger or big toe, and then bony prominences if necessary. See if vibration is felt and how long for (approx. 8 sec is normal)
Graphaesthesia: Can patient recognize a digit traced on their palm?
How do you move when testing sensation?
Move randomly when testing for any numbness
Move from numb area outwards when testing for border of numbness.
What are the three goals of anaesthesia and how are these achieved?
- Hypnosis- normally and IV or volatile agent
- Immobility- normally a muscle relaxant
- Autonomic Areflexia- normally opioids
Modern anaesthesia uses balanced anaesthesia, with different drugs for different purposes
What is the mechanism of uptake and release of volatile agents?
PI > PA > Pa > Pbr (start of anaesthesia)
PI < PA < Pa < Pbr (end of anaesthesia)
How do volatile anaesthetics work?
They likely modulate gaba in the brain and glycine in the spinal cord to reduce synapse transmission
What is the MAC and what factors affect it?
Minimal alveolar concentration producing immobility on standard surgical stimulus in 50% of patients. It is usually expressed as a percentage. The lower the percentage the more potent the drug.
Factors increasing MAC include young age, hyperthermia, hyperthyroid, drugs, and heavy alcohol
Factors decreasing MAC include old age, hypothermia, hypothyroid, drugs, pregnancy and low O2/High CO2
How is volatile anaesthetic dosing monitored?
The FI is compared to the FE, adjusting for minute ventilation, FA and transfer into the blood to estimate blood concentration.
What are the effects of volatile anaesthetics?
Hypnosis, immobility and amnesia
Decreased CMRO2, and increased CBF and ICP- so there are protective and harmful factors for neuro
Peripheral vasolilation, lower BP. Unchanged HR and SV
Resp depression, impaired reflexes to hypoxia and hypercapnia.
Bronchodilation
What are some of the features of NO?
Odourless, non flammable inhaled anaesthetic Low potency Low blood-gas solubility, rapid onset Analgesic Nausea and vomiting
What are some of the features of isoflurane?
Potent inhaled anaesthetic, good CVS stability
What are some of the features of sevoflurane?
Non pungent and least resp. depression- good for gaseous induction anaesthesia
Low solubility, rapid onset
Theoretical renal toxicity
What are some of the features of desflurane?
- Pungent inhaled anaesthetic
- Low blood gas solubility, rapid onset and offset
What are some categories of IV anaesthetic and how do they work?
Barbituates (thiopentone)
Phenols (propofol)
Imidazoles (Etomidate)
Ketamine
Benzodiazepines (Midazolam)
All but ketamines act on GABA receptors to enhance GABA, increase Cl- current and cause hyperpolarization
Ketamines act on NDMA receptors in PCP receptrs to antagonize glutamate, suppress excitation and cause analgesia
How do IV agents act in the body?
They are highly lipid soluble and cross the blood-brain barrier
Drug is taken up by well perfused organs, and then decrease blood concentration and they see a concentration drop as the drug leaves the well perfused organs and is metabolized in the liver or is redistributed to tissues.
Describe some of the properties of thiopentone
Very rapid onset and offset, with slow clearance so accumulation will occur
Metabolized in the liver
Causes decreased PVR and BP, as well as rep depression and reflex loss
Mostly used in emergency cesarians and ED
Describe some of the properties of propofol
Moderately rapid onset and offset, with fast clearance allowing for maintenance infusions
Metabolised in liver
Significant decrease in PVR and BP, resp. depression and loss of airway reflexes
It is the standard IV anaesthetics as it reduces CBF and ICP, has less of a hangover and can be used for maintenance
Describe some of the properties of etomidate
It shows CV stability, less resp depression and rapid clearance. However, it shows adrenocortical inhibition, which prevents HPA axis functioning and reduces stress hormones, which are important for recovery
Describe some of the properties of ketabine
Analgesic
Stimulates CVS and preserves resp reflexes and drive
Increased CMRO2, CBF and ICP so not good for neurosurgery
Good for shock but slow and dysphoric emergence
Describe total intravenous anaesthesia, and its pros and cons
Avoids inhalation, and complications of this (malignant hyperthermia, PONV, increased ICP)
However, it’s expensive and unable to be effectively monitored.
Describe the structure of local anaesthetics
They have a hydrophobic aromatic group at one end, a hydrophilic amide group at the other end, and are linked together by either amides or esters.
How does the link of local anaesthetics affect their properties?
- Esters are more rapidly metabolized, and so have shorter action, and are more allergenic. Amides have the opposite. Additionally, lengthening the alkyl chain length increases the lipid’s solubility, making it more potent.
What are some examples of ester vs amide local anaesthetics?
Esters include cocaine, procaine, benzocaine, tetracaine
Amides are prilocaine, lignocaine, bupivacaine, and ropivacaine
What is the main property of local anaesthetics that determines their speed of action?
Their pKa. The closer their pKa to physiological, the more free base there will be in the body, allowing it to enter the cell and block nerve transmission from the inside
What is the fastest acting local anaesthetic?
Mepivacaine, followed by lignocaine
What does protein binding have to do with duration of action for LAs?
The higher the degree of protein binding, the longer the duration of action.
How are LAs metabolised?
Esters by plasma cholinesterases
Amides by liver metabolism
Describe the properties of lignocaine
Low solubility and potency
Low pKa so fast onset
Low protein binding so short duration
Ideal for short surgical procedures
Describe the properties of bupivacaine
More potent, longer lasting and slower onset compared to lignocaine. May cause cardiac arrest before the neurotoxicity warning sign. Ideal for nerve blocks for analgesia
Describe the general properties of cocaine, prilocaine, and ropivacaine
Cocaine- ester, topical to nose, vasoconstrictor
Prilocaine- amide, safest, used in IV regional anaesthesia with a tourniquet to prevent arrest
Ropivacaine- amide, slow onset, long acting but less CVS toxicity
How do you assess LA toxicity?
Allergic reactions are rare, however, CNS and CVS toxicity can develop, of which CVS is much more life threatening
Thankfully they are dose dependent, and CNS tends to occur earlier than CVS- simply watch for neuro and don’t give any more!
How do you administer LAs topically, and why?
They can be topical to the skin in a mixture of LAs in oil. This allows most to be free base and cross the skin. It is used in insertion of IV cannulae in children
Topical to mucus membranes: Cocain has the added advantage of vasoconstriction. Used for instrumentation of the nose/mouth/pharynx as in awake intubation
How do you administer LAs to the soft tissue?
For minor interventions like a mole removal, you use a fast, short duration agent
For post op pain relief you use a slow, long duration agent
What is a peripheral nerve block?
The LA ins infiltrated around a specific nerve or plexus. Sensory fibers are more susceptible, but motor nerves can also be affected. USed for surgery without a GA, or postop pain relief
What is a neuraxial blockade?
LA is injectd into the intrathecal space below L2. It produces a profound distal motor and sensory block, allowing major distal surgery while awake
What is an epidural anaesthetic?
A small catheter is inserted into the epidural space and LA is infused around the spinal nerves nearby. It can be done at any level, and produces a distal sensory and motor blockade. It allows maintenance infusion, and is excellent for postop and labour analgesia
What do NMBAs do?
They paralyse patients undergoing surgery or requiring intubation. They do not sedate, cause amnesia, or have analgesic effects.
Why are NMBAs necessary for intubation?
They paralyze the vocal cords, decreasing damage and postop hoarseness. It also allows control of ventilation intraoperatively, allowing oxygen consumption to be decreased and barotrauma to be prevented. Ventilating also lowers ICP.
What are the 3 areas of the NMJ and their general functions?
Presynaptic- ACh synthesis and storage. Release of ACh and reuptake of Ch
Synaptic cleft: Side of AChE, ACh crosses
Postsynaptic- AChRs anchored in folds
Describe the events at synapse including quantal theory
ACh is stored in vesicles. Ca2+ flows into the cell after an AP, causing the ACh vesicles to fuse with the presynaptic membrane and release ACh into the cleft. The number released is proportional to Ca2+. usually about 200 units with 5000 ACh each. About half are immediately hydrolysed, though more is released than necessary for a single transmission. Approx. 500000 AChRs are bound, allowing Na+ to flow in and causing endplate depolarization.
Describe AChRs
Ligand gated ion channels with 5 subunits each- 2a, b, y, e. Both a units must be bound simultaneously, causing a conformation change, opening the channel and allowing ions to flow in.
Describe AChE
An enzyme present primarily in the synaptic cleft, and to some extent in the extrajunctional area. It is secreted by the muscle and attached to the basal lamina by collagen.
Describe depolarising muscle relaxants
Known as Sux (suxamethonium). It is similar in structure to ACh, and is comprised of 2 ACh molecules bound together. It mimics the effect of ACh by causing depolarization, although it causes fasciculation (a brief flicker of movement) and then relaxation lasting 3-5 mins. It is not hydrolyzed by AChE, but by pseudocholinesterase. Its neuromuscular blocking activity is terminated by diffusion into the plasma. Its time of action depends on the time taken to excrete it.
What are some of the side effects of Sux?
It cannot be reversed pharmacologically Anaphylaxis Fasciculations and postoperative myalgia Cardiac dysrhythmias Hyperkalaemia Increased ICP, IGP and IOP Malignant hyperpyrexia Masseter spasm
What are the positives of Sux?
It provides the quickest, most reliable relaxation for airway control, giving excellent intubating conditions with minimal time for aspiration. It is mainly emergent
Describe how non-depolarising NMBAs work
They are positively charged quaternary N compounds
They compete with ACh and bind to one or both a subunits, preventing ACh binding and opening of the ion channel. As only one molecule of the drug is required to do this, it is biased towards favouring the antagonist
Blockade starts when receptors are more than 70% occupied, and is complete when more than 90% are occupied
What are the two ways of grouping Non depolarising NMBAs?
Chemical structure: Aminosteroies have ammonium on a steroid- Rocuronium, Vecuronium and Pancuronium. Benzylisoquinolones have 2 ammonium joined by methyl. Atracurium, Cisatracurium and Mivacurium
Duration of action: Short acting (Mivacurium)
Intermediate acting: Atracurium, Vecuronium, Rocuronium
Long acting: Pancuronium
Describe atracurium
A NMBA with an intermediate duration and a 3-5 minute onset. It has 2 elimination pathways- Hoffman is nonenzymatic, and dependent on temperature and pH. Its inactive products are excreted. It is also partly removed by renal excretion and ester hydrolysis. It can cause histamine, hypotension and tachycardia. Its advantages are in elderly or kidney dysfunction patients as it is not dependent on renal excretion
Describe mivacurium
3x more potent than atracurium, slow onset of 3-5 mins short duration of action, hydrolysed by pseudocholinesterases. Less histamine. Used mainly in ambulatory surgery
Describe rocuronium
Rapid onset and intermediate duration. Used for rapid sequence induction instead of Sux, but longer duration. Can have anaphylaxis. 90% hepatic elimination
Describe vecuronium
Intermediate duration. Show onset, but no CV side effects. Active metabolites, renally excreted- means it accumulates in renal failure. Used ful in CVS disease patients, with least anyphylaxis and histamine
Describe pancuronium
Long duration of action, high potency and slow onset. Longest duration. Increases BP, HR and CO, so ideal for long cardiac surgery. Minimal histamines. Difficult to reverse
Describe the perfect NMBA
Rapid onset Titratable effect Easily reversible No histamine or anaphylaxis No haemodynamic effects Inactive metabolites No accumulation Low cost
How can you reverse NMBAs?
You cannot reverse depolarising NMBAs.
Strategies for reversing the others include titrating perfectly for their duration of action, but this is hard as both patients and surgeons can be unpredictable.
Additionally, you could accelerate their reversal, which is safer and more reliable. It can be acheived by increasing the concentration of ACh at the receptor, or decreasing the NMBA.
Increasing ACh is done by using AChE inhibiting drugs, although these act on all receptors throughout the body. This means they have side effects such as bradycardia, bradyarrhythmias, bronchospasm, salivation and increased bowel motility. To counteract these, antimuscarinic agents are given in combination
What is sugammadex?
A perfect antidote for rocuronium and vecuronium, by selectively binding rocuronium and rendering it incapable of binding to the AChR. It favours movement of rocuronium from the NMJ to the plasma, allowing muscle function to return within 2 minutes.
How do you monitor a neuromuscular blockade?
Stimulate the peripheral nerve, assessing the response of the muscle. A stimulator is connected to the ulnar nerve, and 4 stimuli 0.5 seconds apart are given at a frequency of 2hz. The movement of adductor pollicis is assessed, with the TOF count and the TOF ratio. TOF is the number of twitches seen, TOF ratio is the ratio of the 4th to 1st twitch as a percentage.
Intact neurotransmission shows four twitches of identical height.
Recovery from a neuromuscular block causes twitches to come back slowly.
What is TOF fade?
A deficiency of neuromuscular transmission requiring intervention. It is only seen in non-depolarising NMBAs. Different muscle groups respond differently. The diaphragm is less susceptible than peripheral nerves, so adductor pollicis is used as a proxy. It shows
What is double burst stimulation?
The fade of the second twitch is compared to the first. Two to three short bursts of stimuli are administered twice, comparing the twitches. Full recovery is two equal twitches.
What are the five basal ganglia?
The caudate nucleus, putamen (collectively called the striatum), globus pallidus, hypothalamus, and substantia nigra.
What is the function of the basal ganglia?
They smooth out and plan motor movement.
What are the three capsules of the basal ganglia?
The internal capsule, external capsule (separating the claustrum from the putamen) and the extreme capsule (separating the alimentary cortex from the basal ganglia)
What are the claustrum and alimentary cortex?
Claustrum is the centre for visual attention
The alimentary cortex represents the GI system.
Describe the direct and indirect pathways of the basal ganglia
Direct pathway is GLUT from planning area to striatum, GABA to GPi, GABA to VaVL and GLUT to planning
Indirect pathway is GLUT from planning to striatum, GABA to GPe, TABA to subthal, GLUT to GPi, GABA to VaVL and GLUT to planning
What is the nigrostriatal pathway?
Dopamine pathway between the substantia nigra pars reticulata, and then the SN pars compacta to the striatum. It produces dopamine which is then transferred back to the striatum, holding the cells at a tonically active state
How does the pathology of huntingtons disease occur?
The pathway from the striatum to the GPe is inhibited. The fibres from GPe to SUT aren’t inhibited, and are free to inhibit the GLUT pathway to GPi. GPi then in turn inhibits the VaVL less, allowing uninhibited firing of the VAVL nucleus to the planning area.
What are the symptoms of and treatment of huntington’s disease?
Symptoms include behavioural and cognitive changes, hyperkinesia and involuntary movements. It is due to trinucleotide repeats within the base sequences. Males hand down longer copies of repeats, with women handing down the same length. Therefore, genetic anticipation can happen, where longer and longer chains cause the offspring to get it earlier and more violently than their parents.
What are the symptoms of parkinson’s disease, and how does this relate to its
It’s due to a failure of the nigrostriatal pathway, which produces dopamine. The lack of dopamine means that the striatum is unable to fire, leading to hypokinesia, emotionally flat moot, tremor at rest (esp. pill rolling) and rigidity.
It can be treated with oral levodopa (although this can cause toxicity), a pallidotomy, or thalamotomy, on one side of the brain, or deep brain stimulation (an adjustable pacemaker implant)
What are the different nuclei within the cerebellum and what do they do?
Fastigial nucleus: Sends info on proprioception to the reticular formation and lateral vestibular nucleus, to be transferred to the lower montorneuron pool.
The interpositus nucleus sends information on automated movement to the red nucleus, which then sends the information via the rubrospinal tract to LMNs
The dentate nucleus sends info on fine movement to the red nucleus and Vent. Lat nucleus, which then sends it ot UMNs and LMNs.
How is the cerebellum divided and what do each of the parts do?
It has lateral part, intermediate part, and vermis. There is also and anterior lobe, posterior lobe, and focculonodular lobe.
The neocerebellum receives input from pontocerebellar and olivocerebellar fibres, for fine motor control, rebound reflex and correction of movement (ie when somebody bumps into you while walking).
The palaeocerebellum is in the intermediate part, and receives proprioception info from the spinocerebellar fibres and olivocerebellar fibres
The archicerebellum is in the flocculonodular lobe and is the first part to develop. It receives vestibular info from the bod
What happens when there are issues with different parts of the cerebellum?
Issue with neocerebellum means issues with fine movement, like an intention tremor
Issue with the palaeocerebellum means there is an issue with postural instability
Issue with archicerebellum means there are problems with general balance, eye movements become quick, cannot focus.
What are the peduncles of the cerebellum and what goes through them?
The inferior peduncle receives info from the olivocerebellar fibres, and vestibulocerebellar fibres from the inf olive and vestibular nucleus
The middle cerebellar peduncle receives fibres from the pontine nuclei
The superior cerebellar peduncle receives info from the cerebellum’s nuclei and redirects it to the thalamus, vestibular nucleus, inf. olive, spinal cord etc,
Define drug tolerance and sensitization
Tolerance to a drug is the reduction in response to a drug after repeated administrations. It may be innate or acquired. Sensitization is the opposite process
What is physical drug dependence and withdrawal syndrome?
Physical dependence is the state that develops as a result of tolerance, produced by the resetting of homeostatic mechanisms in response to repeated drug abuse.
Withdrawal syndrome is the evidence of physical dependence- usually characterised by CNS hyperarousal. It is characteristic to the drug category and tends to cause the opposite effects of the drug itself. For example, opioids cause restlessness, cravings, nausea, aches, anxiety, tachycardia when withdrawn.
How is the mesolimbic system involved in addiction?
The stimulis hits the ventral trigeminal area, which gives a pleasurable sensation. It then continues through the nucleus accumbens, where it ends in the prefrontal cortex. Dopamine is the important neurotransmitter in this pathway.
What is substance dependence syndrome?
Continued use of a substance despite problems related to it
Tolerance
Withdrawal symptoms
Dependence is three of these (addiction), one or two indicates abuse.
What are the three sources of substance dependence?
The agent, host or environment.
How does the agent create substance abuse?
Reinforcement is the property that makes the user want to take the drug again- associated with central neurotransmitters and the rapidity of onset of the drug and its method of use.
How does the host create substance abuse?
People show variability in their pharmacokinetic response to drugs, pharmacodynamic response, and their behavioural response to drugs. Some people have polymorphic inheritance for propensity to addiction. Innate tolerance also occurs. Some physiological changes prevent addiction (ie. those with increase alcohol dehydrogenase will never be alcoholics)
Psychiatric disorders can also increase the risk of drug addiction
How does the environment create addiction?
Societal norms and their view of addiction. Additionally, peer pressure, low employment and low educational levels are important.
Describe alcohol as an addictive drug
It’s a CNS depressant (but a stimulant at low doses). It impairs recent memory, motor coordination, and causes sedation in high doses.
As tolerance develops, sedation is reduced but the lethal dose is unchanged- more dangerous.
Withdrawal symptoms include craving, tremor, irratability, nausea, tachycardia, etc.
Delerium tremens is caused by long term alcohol abuse and subsequent withdrawal. It shows agitation, confusion, hallucination, sweating etc.
How is alcohol metabolized?
It is metabolized in the liver by alcohol dehydrogynase. The decay is relatively quick for the first few drinks, but changes to zero order once the process becomes saturated, allowing a dangerous buildup.
What can long term use of alcohol cause?
Liver cirrhosis, myopathy, endocrine issues, FAS, mental retardation.
How are opioids as drugs of addiction?
It is used mainly as an analgesic, although its prescription rate has skyrocketed and its affordability plummeted. This has lead people to source cheaper versions from other sources.
There are short acting rapid onsets (morphine, fentanyl) and long acting slow onsets (methadone)
Describe heroin as a drug of addiction
It is the most important opioid of abuse, and is illegal in USA and NZ.
It is associated with abnormal pituitary function, irregular menses, reduced sexual performance, high mortality.
What are the withdrawal symptoms of opioids?
Craving, restlessness, irritability, pain sensitivity, nausea, cramps dysphoria, anxiety
Signs include dilated pupils. sweating, piloerection, tachycardia etc.
Describe cocaine as a drug of addiction
It blocks transporters that recover dopamine from the synapse, leading to increased dopaminergic stimulation. This results in arousal, enhanced performance, increase in HR and BP
Repeated doses lead to stereotyped behaviour, irratibility, violence, and addiction in some users.
Toxicity can result in arrhythmias, psychosis, seizure etc.
Describe meth as a drug of addiction
It releases high levels of dopamine, enhancing mood and body movement. It is neurotoxic, and damages dopamine and serotonin containing cells.
Toxicity includes CNS issues increased wakefulness, increased physical activity, decreased appetite etc.
Describe cannabinoids as a drug of addiction
Burning cannabis leaves contain over 61 cannabinoids, and is the commonest illegal drug in the US. The drug activates cannabinoid receptors in the brain, which results in a high, a reduction in cognitive function, reaction time, learning and memory long term. Anxiety attacks and hallucination may also occur.
Describe propofol as a drug of addiction
- Anaesthetic induction agent with a very narrow therapeutic index
Define epilepsy
A condition in which patients have recurrent, unprovoked epileptic seizures. This comprises an abnormal and excessive electrical discharge from neurones in the cerebral cortex, and is often associated with a loss of consciousness.
What can cause epilepsy?
Can be structural, genetic or metabolic dysfunction
What are the different categories of seizures?
Partial seizures involve neurones in one part of the brain only. A generalized seizure involves all the neurones of the brain
What is the physiology of a seizure?
An imbalance between excitatory and inhibitatory neurotransmitters. It is caused by the synchronous activation of large numbers of hyperexcitable neurones. This can be propogated by normal and abnormal pathways
It can involve GLUT.
NMDA receptors open the channel for Na+, K+ and Ca2_ cations, and is activated by NMDA
Non-NMDA receptors are activated by AMPA and kainic acid, not NMDA. It is permeable to Na+ and K+, but reasonably impermeable to Ca2+. It’s rapidly activated and inactivated
It can also involve GABA. Seizures can be caused by blocking of GABA, activation of GLUT receptors, blocking glycine or K+ channels, and unblocking NMDA receptors.
How do you treat epileptic seizures?
Can block Na+ channels (phenytoin). It stabilizes Na+ currents and prevents repetetive firing from sustained depolarization
It also enhanses GABA and reduces GLUT
What are some mutations that can cause epilepsy?
Na+ channel mutation can cause severe myoclonic epilepsy of infancy (causes intellectual impairment) as well as benign epilepsy
Ca2+ channel mutations in the thalamus cause hyperpolarized thalamic neurons, producing cortical depolarization. It is especially common for absence seizures.
What are the different ways of causing an epileptic seizure?
Anatomic rearrangement of local circuits
Frequency dependent changes in synaptic efficacy
Changes in local receptors
How does anatomic rearrangement of local circuits cause epilepsy?
Excitatory axons have collateral branches activating neurones in local regions of the CNS. They can contribute to feedback inhibition or excitation, of which inhibition is typically more powerful., If there is neuronal death, new circuits grow in to replace them, forming new uninhibited circuits
How does a change in local receptors cause epileptic seizures?
NDMA receptors may change, and it can be either perpetuated by seizures or by mutation from birth. This is the principle of kindling, where a repeated exposure to subthreshold stimulation produces spontaneous seizures.
Describe different generalised seizures
A generalized seizure involves both hemispheres of the brain, and may have major or minor motor manifestations.
Types can be- tonic- sustained contraction of muscle
Clonic- regular repeated jerks
Tonic clonic- sustained followed by jerks
Myoclonic- brief jerks of axial and limb muscles
Epileptic- brief contractions of limbs and axial, with an initial myoclonic component.
Absence- go completely blank
Frontal lobe- sudden, abrupt limb posturing
Describe partial seizures
They preserve consciousness, and only involve a certain part of the brain
Can be visual, somatosensory, auditory, psychic, abdominal, olfactory, versive, or focal motor
Complex partial seixures have a loss of consciousness and are unresponsive.
Why do we need sleep?
Most likely to do with synaptic shrinkage. This allows the brain to tidy up and lose unnecessary memories, to permit the formation of new circuits the next day
What are the different sleep stages?
1- on the verge of sleep 2- light sleep 3- deep sleep 4- unwakeable REM- dreaming
What sort of things are necessary to ask in a sleep history?
Sleep onset, interruptions, quality, extra sleep features (ie snoring, sleep walking)
