Week 19 - Peripheral Neuropathy

Question 1

Explain the blood-nerve barrier.

Answer 1

Barrier between the inner perineurium and endothelial cells of miscrovasculature within endoneurium

Question 2

What are the two types of schwann cells?

Answer 2

Myelinating and ensheathing

Question 3

What are the two main variables that influence AP propagation rate?

Answer 3

Diameter and myelination.

Question 4

Describe the two classification schemes of neurons.

Answer 4

ABC which indicates conduction velocity.

Roman numeral 1-4 which indicates diameter and is used for sensory axons.

Question 5

Describe how Ach is made and is transported down the axon.

Answer 5

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.

Question 6

Describe a nicotinic Ach receptor.

Answer 6

5 subunits surrounding central pore with diff configurations possible.
Two molecules of Ach bind and open pore conducts Na and K ions.

Question 7

Name some presynaptic and postsynaptic NMJ pathologies.

Answer 7

Pre
- guillian barre, polio, botulism
Post
- myasthenia gravis

Question 8

Describe segmental demyelination.

Answer 8

Mildest form of nerve damage (called neuropraxia)

- reduction in myelin thickness, complete demyelination, or complete demyelination of several segments.

Question 9

Describe the process of remyelination.

Answer 9

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.

Question 10

Describe the effect on conduction studies in different neuropathies.

Answer 10

Segmental demyelination
- increased latency
Axonal loss
- decreased amplitude

Question 11

Can healthy peripheral neurons regenerate? If so, how many mm per day?

Answer 11

Yes. 1-4 mm.

Question 12

Describe the axon regeneration process. Do they find their appropriate targets?

Answer 12

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).

Question 13

What happens if a cut nerve is not repaired? What is the time limit for repair?

Answer 13

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.

Question 14

If a nerve is cut, does it matter how far the cut is from the distal site?

Answer 14

Yes! The farther away, the worse recovery.

Question 15

Can you tell the diff between neuropraxia and axon damage at time of injury?

Answer 15

No. But in three months you can because neuropraxia has had a chance to occur.

Question 16

What four pieces of info do our sensory receptors tell us about?

Answer 16

Modality, intensity, duration, and location.

Question 17

What is synesthesia?

Answer 17

Stimulation of one sensory pathway leads to involuntary stimulation of another.

Question 18

How is stimulus intensity coded by neurons?

Answer 18

One fibre fires more (temporal) or more fibres fire (spatial).

Question 19

What is an example of a slowly adapting vs fast adapting receptor?

Answer 19

Merkels discs are slow adapting and pacinian corpuscles are fast adapting (their outer shell absorbs the deformation).

Question 20

What is the sensory resolution on the back vs the finger?

Answer 20

Back = 30-40 mm
Finger = 1-2 mm
This is all due to receptor density and the size of the receptive fields.

Question 21

How is receptor modality encoded?

Answer 21

By the type of receptors and where its neuron terminate in the brain.

Question 22

Discuss the relevance of local anaesthetics being amphoteric.

Answer 22

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.

Question 23

Discuss what changes the potency, onset of action and duration of action for local anaesthetics.

Answer 23

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

Question 24

Describe the routes of administration for local anaesthetics.

Answer 24

Topical - corneal, mucous membrane, epidermal
Infiltration anaesthesia
Peripheral nerve blockade
Central blockade (epidural, subarachnoidal)
Systemic (IV)

Question 25

Describe the phases of systemic CNS toxicity.

Answer 25

Starts with inhibition (sedation, dizziness, tinnitus), then it becomes excitatory (tremor, myocloni, seizures), then it becomes depressive (coma, cardiorespiratory arrest, death)

Question 26

What is the diff between bupivacaine and ropivacaine?

Answer 26

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.

Question 27

What does the epineurium, perineurium, and endoneurium encapsulate respectively?

Answer 27

Entire nerve, bundles of axons called fascicles, contained within the perineurium consisting of axons.