WEEK 4 Flashcards
What causes Upper Motor Neurone signs
Damage to any aspect of the UMN
What causes Lower Motor Neurone signs
Damage to any aspect of the LMN or death or dysfunction to the muscle (disorders of MN’s soma/axon or NMJ)
Define innervation
normal state of nerve supply to a muscle/other target
Define denervation
depriving the muscle of its nerve supply
Define re-innervation
regrowth of the nerve to re-supply the muscle after denervation
What is often the result of re-innervation?
Original effector organ not always re-innervated, different effector organ innervated instead
Example of unsuccessful re-innervation
Crocodile tears syndrome due to re-innervation of tear glands from salivary glands-crying when smell/see food
What are the implications of disorders of a motor neurone’s cell body?
Loss or damage to the MN’s cell body (soma) leading to death of the MN
What is Polio Myelitis?
Communicable disease (polio virus) targeting LMN cell bodies in the ventral horn (known as infantile paralysis)
What is indicative of Polio Myelitis?
Atrophy (shrinking) of ventral (+dorsal) horns of spinal cord
What is the overall effect of Polio Myelitis?
Death of MNs leading to denervation hence paralysis of muscles they supply
What are the two variants of Motor Neurone Disease?
disease simultaneously killing UMN + LMN (progressive supranuclear palsy)
disease targets only LMN
What causes MND?
Spontaneous genetically programmed death (apoptosis) of body’s MN
Which motor neurones aren’t susceptible to MND?
MN supplying extraocular and anal sphincter muscles (neural root values S2-S4)
What are the implications of disorders of a motor neurone’s axon?
Loss or damage to MN’s axon doesn’t necessarily lead to MN death, however leads to denervation
What are two causes of MN axon disorders?
Complete transection of axons of MN (due to crushing/stabbing injuries)
Demyelination of axons of MN (Guillain-Barre Syndrome/Peripheral neuropathies)
How is Guillain-Barre syndrome acquired?
A complication following viral infection such as a common cold
What is caused by diabetic neuropathy?
Demyelination of both sensory and motor axons
What occurs with Guillem-Barre Syndrome when condition is cured/goes into remission?
Reversal of clinical signs
What are 3 examples of diseases to the NMJ?
Botulinum toxin (Botox)
Nerve gases
Myesthenia Gravis
What is Botulinum toxin (botox) and what effects does it have on the NMJ?
A toxin that depletes the Pre-S terminal of NMJ of it’s neurotransmitter causing paralysis of body muscles and potential death
What are nerve gases and what effects do they have on the NMJ?
A class of phosphorus-containing organic chemicals that block AChE from breaking down ACh in the NMJ
Myesthenia Gravis
explained in previous week
What are the implications of disorders of the muscle?
LMN sings of myogenic origin
Give an example of a disorder of the muscle
Duchenne Muscular Dystrophy
What is Duchenne Muscular Dystrophy?
Genetic condition resulting in progressive muscle weakness due to defects in muscle proteins, eventual death of individual
Give four examples of LMN signs
Muscle atrophy (shrinking) due to denervation, Ptosis (drooping of eyelid(s)), Fasciculations (muscle twitching), negative Babinski (Plantar) reflex
What is a local anaesthetic?
A medication that reversibly blocks nerve conduction when applied to a restricted area of the body to enable a procedure to be carried out without loss of consciousness
What is the difference between LA and GA?
LA acts on restricted area, GA is body-wide/results in loss of consciousness
Why are local anaesthetics used?
To prevent pain (nociception->senory receptor->AP-x->brain)
Naming convention of local anaesthetics
-caine (suffix)
What is the chemical structure of local anaesthetics?
aromatic ring-linkage-basic amine group
What is the linkage for LAs?
Amide or ester
What is the purpose of the linkage?
Site of metabolism (enzyme action)
Which linkage has the faster rate of metabolism?
Ester
What are the two key implications to consider for clinical use of LA?
Metabolism long enough to sustain procedural length and no allergic/toxic metabolites
What does the aromatic ring of LA allow?
Lipid solubility (not if molecule is charged)
What does the amine group of LA allow?
Ionisation (accepts proton)
Are local anaesthetics weak acids/bases?
Weak bases
What is the equation relating to LA ionisation?
LA + H20 ⇌ LA+ + OH-
What determines LA ionisation state?
pH (increased acidity=more ionised (lipophobic), increased alkalinity=less ionised (lipophilic))
Mechanism of LA action
unionised LA enters the cell due to lipophilicity, becomes ionised due to more acidic pH, ionised LA blocks V-gated Na+ ion channels, prevents Na+ influx, cells can’t depolarise
What is use-dependent blocking?
Degree of block depends on whether channel is being used (LA+ block open channels therefore increased pain=increased block)
What factor affects LA effectiveness and how is this altered?
Tissue pH which is made more acidic by inflammation/infection due to bacteria, causing more ionised LA-need proportion of LA to be unionised to travel through membrane
Explain what is meant by different neurone sensitivity
Motor neurones are much less sensitive to LA than nociceptive axons due to having a much thicker axon, so are less affected
What is the general principle of LA administration?
The more proximal the site of administration, the greater the area affected
What is topical administration?
anaesthetising the skin or throat, not very effective as LA mol. can’t diffuse as quickly through densely packed skin cell structure
What is infiltration administration?
injection into the skin, potentially a series of injections around area (eg. ‘ring block’)- eg. skin stitching
What is nerve block anaesthesia?
injection given quite proximally- eg. whole/half jaw anaesthesia
What is epidural anaesthesia?
injection into epidural space, into vertebrae not spinal cord therefore affecting nerve roots exiting spinal cord- eg. child birth
What is spinal anaesthesia?
injection into CSF in subarachnoid space affecting spinal nerves in that space and spinal cord
Side-effects of anaesthesia
Non-specific=related to other substance in LA solution-hypersensitivity (allergic) reactions
Specific=related to blocking of V-gated Na+ channels-high doses/injection into wrong area
What are the other drugs administered with LA?
Preservatives
Vasoconstrictors-localise LA to decrease unwanted effects and increase duration of action
