Week 1 Flashcards
Sympathetic NS rhyme
Fight or flight
HR increased
Guy activity decreased
Parasympathetic rhyme
Rest and digest
Each part of symp and para consists of two types of neuron?
Pre ganglionic and post ganglionic
Cell body in CNS - axon enters PNS …
Cell body in PNS - inner aged target organ …
Preganglionic
Post ganglionic
Where is postganglionic cell located
In a ganglion
Where are preganglionic neurons
Symp- in thoracic and upper lumber spinal cord ( leave in spinal nerves T1 - L3
Para - brainstorm (leave in some cranial nerves) and sacral spinal cord ( leave in spinal nerve S2-S4 )
Where are the ganglia
Symp ganglia are mainly found in sympathetic chain(trunk) located next to vertebral column
Para ganglia are located in the Walls of the viscera they innervate
meninges
tough connective tissue surrounding and protecting the CNS
total segments of the spinal cord
31 total 8 12 5 5 1
cervical nerves C1 to 7 pass through the intervertebral foramen at what point?
above their appropriate vertebrae
C8 to coc 1 pass through the intervertebral foramen at what point?
below their appropriate vertebrae
where is the lower limit of the spinal cord in an adult ?
L1/L2 border
what does the neural tube develop from
from a flat plate of cells - neuro-ectoderm
plate forms a tube central canal surrounded by nervous tissue - grey and white matter.
Alar plate ?
Basal plate?
aspects of the spinal
Dorsal (sensory)
ventral( motor outputs to periphery)
(cord at time of development )
different types of SB
occulta, lipomeningocele, meningocele, myelomeninggocele (increasing in severity)
Main features of the grey matter?
Dorsal horn
immediate horn (connects dorsal horn to central horn )
ventral horn
dorsal and ventral aspects are bigger in which segments of the spinal cord?
cervical and lumbar.
innervating the limbs (accommodation of muscles to consider)
the outermost layer of spinal cord?
Dura mater.
a think inelastic membrane, fuses with the endosteum of cranium at the level foramen magnum .
guves rise to the epidural space
MIDDLE meningeal layer?
Arachnoid mater
- much thinner than dura mater, thin fibrous membrane , bridges the subarachnoid space
CSF
a filtrate of blood made in the choroid plexus within the ventriculatr system of the brain . Affords mechanical and immunological protection to the brain and SC.
500 ml produced a day
subarachnoid space contains …
trabeculae, veins and CSF
what plexus of veins exits in the epidural space?
vertebral/baston venous plexus - major rote in spread of cancer from deep pelvic regions
what is the Artery of Adamkiewicz?
-supplies loew 1/3 of spinal cord
-typically arises from left post. intercostal artery
asscoiated with spinal artery syndrome ( loss of urinary and or faecal continence , impaired motor function of legs / spasticity)-
what is found in the ganglions?
cell bodies of the sensory fibres
lowest portion of the spinal cord
conus medullaris
filum terminale
thin filament attaches the spinal cord in place
site of epidural injections ?
lumbar cistern - L3/4 L4/5 vertebral level ( supracristal line passes through body of L4 )
4 main classes of axons
A alpha (largest myelin sheath -emminate from motor neurons, proprioceptors ) A beta (mechanoreceptors of skin) A delta (pain and temperature) C fibres - unmyelinated( temperature , pain and itch)
what does a myelin sheath do ?
speeds up conduction of electrical impulses
Tracts of myelinated axons
ascending (sensory) and descending ( modulate activity
Ascending pathways
discriminative touch - dorsal column pathway
pain - spinothalamic pathway
descending pathways
motor
- muscle tone
- voluntary ( corticospinal corticobulbar)
what is a neuron
communicating unit of the NS
- highly specialised to transmit info from one cell to another.
• Electrically excitable → ability to signal to other
cells
• Communicates via action potentials and
synaptic transmission
what is the resting membrane potential?
Arises due to a difference in charge (due to
ions) between the inside and outside of the
neuron at rest
• More +ve ions outside cell / more –ve ions
inside cell
• Measured in relation to outside, therefore RMP
is a –ve value
• Typical RMP of neurons -60mV to -70mV
what is the distribution of ions across the membrane of a typical neuron
extracellular - Na (high) K (low) Cl (high)
intracellular - opposite
what is the equilibrium potential ?
membrane potential where No
ions entering cell =
No
ions leaving cell (no net gain or loss of ions). concentration gradient and electrical gradient cancel each other out.
what does the opening and closing of voltage gated channels depend on?
membrane potential
what does the opening of a ligand gated channels depend on?
= opened in response to binding /
activation by neurotransmitter or drug
what is an action potential?
• An action potential is
a very brief, but
dramatic change in
membrane potentia
what is depolarisation related to?
Depolarisation related to
increased permeability
to Na+
ions
Repolarisation and
hyperpolarisation due to….
Repolarisation and
hyperpolarisation due to
increased permeability
to K+ ions
Action potential summary?
• Very brief, but dramatic change in membrane
potential
• All or nothing response
• Changes in membrane permeability to Na+ & K+
• Depolarisation: fast opening of voltage-gated Na
channels (Nav
)
• Repolarisation / hyperpolarisation: slow opening
of voltage-gated K channels (Kv
)
what is the propagation of the action potential?
Opening of voltage-gated Na channels during action potential → depolarises axon either
side of depolarised zone reaching threshold → opening of voltage-gated Na channels
how can a positive charge travel?
- along axon or 2. out of axon via
membrane
what does myelin do?
saltatory induction - action potential jumps between gaps - no leakage - action potentials travel much faster
Destination of current depends on …
- axon diameter and 2. number of
open pores / channels in membrane
synaptic transmission ?
chemical transmission between excitable cells
7 steps to synaptic transmission?
1. AP enters presynaptic terminal 2. Ca2+ entry through voltagegated Ca2+ channels 3. Docking of synaptic vesicles containing neurotransmitters 4. Neurotransmitters released (exosytosis) 5. Neurotransmitter binds to and activates receptors on postsynaptic membrane 6. Ions (Na+ / Cl) enter cell 7. = depolarisation (excitation) or hyperpolarisation (inhibition)
what does an excitatory post synaptic potential do?
An EPSP brings the post-synaptic membrane closer to threshold
(depolarisation), therefore increasing the probability of the postsynaptic
cell producing an action potential
Inhibitory postsynaptic
potential (IPSP)?
An IPSP moves the post-synaptic membrane further away from threshold
(hyperpolarisation), therefore reducing the probability of the postsynaptic
cell producing an action potential
types of neurotransmitters
- Cholinergic
- acetylcholine
- Biogenic amines
- catecholamines: noradrenaline, adrenaline, dopamine
- 5-hydroxitryptamine (5-HT / serotonin)
- Amino acids
- excitatory: glutamate
- inhibitory: gamma-aminobutyric acid (GABA)
- Neuropeptides
- endogenous opioids
- Miscellaneous
- gases: nitric oxide
- pruines: adenosine, ATP
Precentral gyrus is posterior or anterior to central sulcus ?
Anterior
Motor homunculus refers to what gyrus ?
Precentral gyrus
Broccas area?
Motor component of speech . Damage leads to slow speech
Wernickes area ?
Sensors language area
Damage - aphagia
Normally left hemisphere
Influences motor activity and motor control
Basal ganglia
Corpus striatum
Causdage nucleus
Putamen
Globus pallidus
Basal ganglia
Corpus striatum
Sub thalamic nuclei
Substantia Nigra
Parkinson’s
Huntingtons
Due to damage disease of what
Substantia nigra
Corpus Stratium
What sends info between two hemispheres
Corpus callosum
Helps generate and synthesise what
Cerebrospinal fluid
What is a dermatome ?
An area of the skin supplied by nerves from a single spinal nerve route
Info carried , myelin sheath, diameter and conduction speed of A-alpha nerve fibres?
Proprioception
Myelinated
13-20
80-120m/s
Info carried , myelin sheath, diameter and conduction speed of A-beta nerve fibres?
Touch ( mechanoreceptors)
Myelinated
6-12
35-90m/s
Info carried , myelin sheath, diameter and conduction speed of A-delta nerve fibres?
Nociception(mechanical and thermal)
Myelinated
1-5
5-40m/s
Info carried , myelin sheath, diameter and conduction speed of C nerve fibres?
Nociception
Non-myelinated
0.1-1.5
0.5- 2 m/s
chemical transducers associated with pain include what?
And what do they do?
Peptides - bradykinin
Lipids - prostaglandins
Neurotransmitters - serotonin , 5HT and ATP
Neurotrophins - NGF
They sensitise ( lower the threshold ) or excite the terminals of the nociceptor by interacting with cell- surface receptors expressed by the neurons
what is pain
unpleasant sensory and emotional experience associated with actual or potential tissue damage
what is
nociception?
nociception mechanism by which an individual detects the presence of a potential tissue harming stimulus.
transduction , transmission, modulation, perception
what is allodynia?
pain from a stimulus not normally painful.
….analgesia
when mildly painful stimulus is much more painful than normal
what does the monosynaptic reflex involve
a proprioceptive afferent and a motor neuron .
example of monosynaptic reflex
muscles contain muscle spindles, which provide info about the stretching of the muscle . this info is conveyed to the CNS by proprioceptive afferents , the largest of which are called Ia afferents. among their connections, these afferents form excitatory synapses onto the motor neurons that supply the same muscle. passive stretching of the muscle will activate the afferents which will inturn excite the motor neurons , leading to contraction of the muscle.
what is a tract ?
consists of groups of axons which travel together and have a common origin and destination. they are usually named from the location of their cell bodies and target of their axons
what are ascending tracts
consists of axons which pass up to the brain from the cell bodies in the spinal cord or dorsal root ganglion. they relay sensory info that the spinal cord receives from primary afferents to the brain. much of this info passes through the thalamus to reach the cerebral cortex where it is consciously perceived
descending tracts
pass from cells in various parts in the brain to the spinal cord . they are concerned with control of movement , as well as regulation of autonomic and sensory functions.
sensory tranduction is detected by nociceptors , in the skin what are examples of these
free nerve endings - pain temp merkels disc - touch meissners corpuscle - touch pacinian corpuscle - vibration ruffini's ending - stretch
example of transducer receptors
TRPV2 - detects heat TRPV1 - heat and acid ASIC - acid and mechanosensation TRPM8 - cold TRPA1 - irritats , mechanosensation, cold
IN DORSAL HORN , the superficial laminae is made up of
lamina I + II
IN DORSAL HORN , the deep laminae is made up of
lamina III + VI
SOURCES OF LOWER BACK PAIN
disc- bulge/rupture vertebrae - lumbar instability,OA joints - facet , sacroiliac muscle- paravertebral, gluteal ligaments - anterior/posterior longitudinal
what kind of pain a a herniated disc and lumbar radicular pain
twwo types of pan
- constant ache , throbbing due to activation of local nociceptors
- shooting , burning pain in the footdue to ectopic discharges from nerve root lesion
how to assess chronic pain
NRS - numerical rating
VRS - verbal rating
VAS- visual analogue
co morbid symptoms associated with neuropathic pain
poor appetite anxiety depression drowsiness lack of energy difficulty sleeping
how does codeine work as an analgesia
it is metabolised to morphine by cytochrome P450 CYP2D6
WHEN PRESCRIBING OPIOIDS what is to be considered
appropriate pain model, pain patient (screen for risk of dependancy and addiction), pain prescription(drug , dose, duration)
neuropathic analgesics
anti-depressants - amitriptyline
anti-convulsants - gabapentin , pregabalin
anti-arrhythmics - lidocaine
harmful beliefs - 4 Ps
progressive pathology
passive ( sickness behaviour , extended rest)
dePression
Problems (social withdrawal, work, financial, legal claim)
psychology input to chronic pain
clinical explanation education classes support groups - pain association pain management programme 1:1 psychology
From which early embryonic tissue is the adult cerebellum derived?
metencephalon
the 3 divisions of the trigeminal ganglion
opthalmic V1
Maxillary V2
Mandibular V3
where does the maxillary branch of CN V leave the skull
the foramen rotundum
-infraorbital foramen
where does the opthalmic branch of CN V leave the skull
the superior orbital fissure
- supraorbital foramen
where does the madibular branch of CN V leave the skull
the foramen ovale
-mental foramen
The cribriform plate of the ethmoid bone is
a sieve-like structure between the anterior cranial fossa and the nasal cavity. fibres of the olfactory nerve pass through the holes
drug entry to the CNS is severely restricted by the
blood brain barrier
the blood brain barrier function to
- maintain a constant environment
- protect brain from foreign substances
- protect brain from peripheral transmitters
WHAT ARE THE Multiple routes of administration for drug entry to the CNS and what are approaches to aid entry?
enteral - lipophilic drugs
perenteral
invasive routes (intrathecal).
prodrugs - L-DOPA
carrier molecules
trasient BBB disruption - mannitol
Anxiolytics and sedatives
Definition: drugs that cause sleep and reduce anxiety
Antischizophrenia (antipsychotic) drugs
Definition: drugs that are effective in relieving the
symptoms of schizophrenic illness.
“typical” - e.g. chlorpromazine, haloperidol
Antidepressant drugs
Examples:
- monoamine oxidase inhibitors (phenelzine)
- tricyclic antidepressants (imipramine)
- SSRIs (fluoxitine)
- Rapid onset (~10 mins) - (ketamine)
Psychomotor stimulants
drugs that cause wakefulness and euphoria
Examples:
• cocaine, amphetamine (e.g. Vyvanse for ADHD)
• methylphenidate (Ritalin)
• caffeine
. Psychotomimetic drugs
drugs that cause disturbances of perception and of behaviour, that cannot be simply characterised as sedative or stimulant effects • Examples: • LSD • mescaline • ketamine, phencyclidine • THC
Cognition enhancers
drugs that improve memory and cognitive performance Examples: • galantamine, donepezil (AChE inhibitors – Alzheimer’s disease)
clinical importance of dopamine in the CNS
- Parkinson’s disease
- Schizophrenia
- Hormone regulation
- Addiction
- Vomit/sickness..
Different dopamine pathways
nigrostriatal - motor control - parkinsons
mesolimbic/cortical -behavioural effects - schizophrenia
tuberohypophyseal - prolactin secretion - galactorrhoea
what causes parkinsons
degeneration of the nigrostriatal dopamine pathway - required for fine motor control. disease characterised by a tremor , hypokinesia , rigidity . substantia nigra is diminished in parkinsons.
aging , synuclein gene , toxins
Parkinson’s disease pharmacotherapies
Therapies aim to ENHANCE dopaminergic signalling in this pathway
- Replace dopamine (precursor - L-DOPA – crosses BBB) effective 1st 5 yrs
- Mimic the action of dopamine (D2/3 agonists -
bromocriptine) effective in some (side effects) - Reduce breakdown of dopamine (MAOIs - selegiline)
side effects of dopamine agonists
hallucinations
pathological gambling / shopping
Schizophrenia
Problems with DA theory:
- D2 receptor blockade is immediate, but therapeutic benefit
takes weeks to appear - Some patients do not respond, despite D2 receptor
blockade - These drugs are effective against the positive symptoms,
but not against the negative and cognitive symptoms.
what is the tuberoinfundibulum system
group of short neurons that run fro the hypothalamus (arcuate nucleus) to the median eminence.
DA cell bodies in arcuate nucleus of the hypothalamus, terminals in median eminence, secrete DA into the portal blood vessels leading to anterior pituitary
how does dopamine affect prolactin
• DA binds to D2 DA receptors on the
prolactin-secreting cells to inhibit prolactin
secretion
