GA E-Learning Module Flashcards
what is the structure of a nerve>
A nerve is a bundle of axons surrounded by a protective sheath called the epineurium. They also have blood vessels to provide nutrients. Within the nerve the axons are bound together in groups called fascicles surrounded by a sheath called the perineurium.
what is the function of the Type Aalpha fibre?
proprioception motor
12-20uM
heavy mylienation
what is the fucntion of the type Abeta fibre type
touch and pressure
5-12uM
heavy mylienation
what is the function of the type A gamma fibre type?
muscle spindles
3-6uM
heavy mylienation
what is the function of the delta type A fibre?
pain and pressure
2-5uM
heavy myelination
what is the function of type B fibres?
preganglionic ANS
<3uM
heavy myelination
what is the function of type C sensory fibre types?
pain
0.3-1.2uM
no myelination
what is the function of the type C sympathetic fibre type?
postglaglionic
0.2-1.3uM
no myelination
what are the two most important fibres for pain?
type A gamme and the sensory fibres
what is the structure of the dorsal root ganglion?
Their cell bodies, located in the dorsal root ganglia, have a single axon that splits (“bifurcates) with one branch going to the periphery and the other into the spinal cord. C fibre sensory neurones also lack myelination.
what are nociceptors?
- Pain-sensing neurones are known as nociceptors or nociceptive neurones.
- The peripheral axon terminal of these neurones is a bare nerve ending that possesses receptors for noxious stimuli such as high or low temperatures and mediators such as H+ and ATP that are released by damaged tissue.
- They can also respond directly to mechanical stimuli.
- Activation of receptors to noxious stimuli generates action potentials that are transmitted from the periphery to the spinal cord (via the dorsal root ganglion). Some nociceptors respond to only a single type of noxious stimulus.
- Others, termed polymodal nociceptors, contain receptors for several types of stimulus.
what is the mechanism of action of LA?
Local anaesthetics act by blocking sodium channels
Therefore:
Local anaesthetics block action potentials
Therefore:
Local anaesthetics block nociception
what is the structure of voltage gated sodium channels?
- Voltage gated sodium channels are large proteins with structural similarities to calcium channels and potassium channels. They are also known as voltage sensitive sodium channels (VSSC). They consist of several different subunits but the main, pore forming subunit is the alpha subunit.
- The alpha subunit is a long chain with 24 membrane spanning domains. This structure is subdivided into 4 blocks of six transmembrane (TM) domains, termed pseudo-subunits. Each pseudosubunit forms a structure a bit like an individual subunit (hence the name). Within each pseudosubunit there are two key structures:
- The charges in the four TM4s move when the electrical field changes. It is this movement that causes the ion channel to open and close
- The membrane dipping domains from each subunit cluster in the centre of the protein to form the lining of the channel. The figure below shows the four pseudosubunits in the membrane. P indicates the pore.
how do sodium channels work?
The three main states of the sodium channel are:
• Closed/Resting: predominates at the resting membrane potential (-70 mV)
• Open: the activation gate opens and the channel starts to enter the open state at membrane potentials above threshold (about -55 mv)
• Inactivated: the activation gate stays open but the inactivation gate closes: this state starts to predominate as the action potential reaches its peak (about +40 mV)
what is the main structure and mechanims of LA?
Most local anaesthetics are variations on the structure of cocaine. They have an aromatic group, an amine group and either an ester or amide group linking the two.
Amide linked local anaesthetics are broken down in the liver while ester linked ones are broken down by plasma esterases. Usually you can recognise amide linked drugs because the prefix (bit in front of ‘caine) will contain an ‘i’. Amide linked drugs tend to have a longer duration of action than ester linked.
