Week 19 - Peripheral Neuropathy Flashcards
Explain the blood-nerve barrier.
Barrier between the inner perineurium and endothelial cells of miscrovasculature within endoneurium
What are the two types of schwann cells?
Myelinating and ensheathing
What are the two main variables that influence AP propagation rate?
Diameter and myelination.
Describe the two classification schemes of neurons.
ABC which indicates conduction velocity.
Roman numeral 1-4 which indicates diameter and is used for sensory axons.
Describe how Ach is made and is transported down the axon.
Precursors are made normally in the cell body, get transported down the axon on MT tracks using energy and oxygen. Then acetyl CoA and choline combine to form Ach where it is stored in vesicles.
Describe a nicotinic Ach receptor.
5 subunits surrounding central pore with diff configurations possible.
Two molecules of Ach bind and open pore conducts Na and K ions.
Name some presynaptic and postsynaptic NMJ pathologies.
Pre
- guillian barre, polio, botulism
Post
- myasthenia gravis
Describe segmental demyelination.
Mildest form of nerve damage (called neuropraxia)
- reduction in myelin thickness, complete demyelination, or complete demyelination of several segments.
Describe the process of remyelination.
Requires trophic factors and cytokines released from schwann cells and affected axons. This triggers the proliferation of undifferentiated schwann cells to become myelinated schwann cells.
Describe the effect on conduction studies in different neuropathies.
Segmental demyelination
- increased latency
Axonal loss
- decreased amplitude
Can healthy peripheral neurons regenerate? If so, how many mm per day?
Yes. 1-4 mm.
Describe the axon regeneration process. Do they find their appropriate targets?
Nucleus responds to lack of retrograde signals by upregulating genes for growth. Sprouts are then produced at the cut ends with a growth cone at each tip trying to find the right receptors.
Seems to be preferential innervation (motor will go to muscle).
What happens if a cut nerve is not repaired? What is the time limit for repair?
Small gap - some axons make it and some don’t. Conduit can be used to guide growth.
Large gap - neuroma will form (scar tissue on nerve)
12 months is the limit before the muscle cannot be innervated again.
If a nerve is cut, does it matter how far the cut is from the distal site?
Yes! The farther away, the worse recovery.
Can you tell the diff between neuropraxia and axon damage at time of injury?
No. But in three months you can because neuropraxia has had a chance to occur.
What four pieces of info do our sensory receptors tell us about?
Modality, intensity, duration, and location.
What is synesthesia?
Stimulation of one sensory pathway leads to involuntary stimulation of another.
How is stimulus intensity coded by neurons?
One fibre fires more (temporal) or more fibres fire (spatial).
What is an example of a slowly adapting vs fast adapting receptor?
Merkels discs are slow adapting and pacinian corpuscles are fast adapting (their outer shell absorbs the deformation).
What is the sensory resolution on the back vs the finger?
Back = 30-40 mm
Finger = 1-2 mm
This is all due to receptor density and the size of the receptive fields.
How is receptor modality encoded?
By the type of receptors and where its neuron terminate in the brain.
Discuss the relevance of local anaesthetics being amphoteric.
They dissociate and form an equilibrium between cation and uncharged form. The base can penetrate through lipid membranes, then becomes cationic and blocks the inside of the Na channels. As the pka goes up, the % of the drug in base form goes down, so it will be less effective. If the pka of the drug is less than the ph of the tissue, more of it will be in base form.
Discuss what changes the potency, onset of action and duration of action for local anaesthetics.
Potency - lipid solubility
Onset of action - lower pka, the faster it works (more base)
Duration of action - increases with lipid solubility and level of protein binding
Describe the routes of administration for local anaesthetics.
Topical - corneal, mucous membrane, epidermal
Infiltration anaesthesia
Peripheral nerve blockade
Central blockade (epidural, subarachnoidal)
Systemic (IV)
Describe the phases of systemic CNS toxicity.
Starts with inhibition (sedation, dizziness, tinnitus), then it becomes excitatory (tremor, myocloni, seizures), then it becomes depressive (coma, cardiorespiratory arrest, death)
What is the diff between bupivacaine and ropivacaine?
Bupivacaine is a racemic mixture with high cardiotoxic effects (particularly r isomer). Ropivacaine is purely the S isomer, so it is less potent and less toxic.
What does the epineurium, perineurium, and endoneurium encapsulate respectively?
Entire nerve, bundles of axons called fascicles, contained within the perineurium consisting of axons.
