Week 5 Flashcards
What do neurones supply
Skeletal muscles via somatic nervous system
Smooth muscles via autonomic nervous system
Glands via autonomic nervous system
Causes for degeneration of nerves
Acquired causes through injury
Genetics of body
Natural processes of ageing
Which neurones have capacity to regenerate and re-innervate effectors
Injured peripheral nerves
CNS neurones don’t regenerate as readily
What does the extent of dysfunction and its severity depend on
Nature of the insult to neurone (or its environment)
Structural features of neurone likely to be affected by insult
Epineurium (superficial)
Perineurium
Endoneurium
Myelin sheath
Axon (deepest)
What attaches adjacent nerve fascicles
Interfascicular bands
What is the system of classification of injuries to nerves based on
Degree to which insult reaches depth of tissue
The measure of depth of tissue is given by layers of ensheathing connective tissue
Seddons’ classification of nerve injuries
Neuropraxia
Axonotmesis
Neurotmesis
What is neuropraxis
When a neurone temporarily loses its ability to function normally this is known as neuropraxis
-injury would be most probably at level of myelin sheath only
-restoration of function would be complete, upon recovery
What is axonotmesis
Usually result of a severe crush injury to a peripheral nerve
Axons of nerve together with their myelin sheaths are damaged
The endoneurium, perineurium, epineurium remain intact
Motor and sensory nerves are affected in same way
Restoration of function can be expected to return fully
What is neurotmesis
When the entire nerve fibre is completely transected or severed
It’s the most severe class of nerve damage according to seddon’s classification system
The axon and connective tissue of nerve are all damaged
Recovery of function doesn’t occur in such nerve injuries
What is the proximal segment
Likely to continue to receive support of cell body
Survives injury
What is the distal segment
Often cut off from cell body
Loses potential for repairs
Loses potential for nutritional support
Becomes vulnerable to phagocytosis by glia
3 classes of glial cells
Myelin forming cells- oligodendrocytes, Schwann cells
Astrocytes- create an environment in which neurones thrive
Microglia- these are immune cells of nervous system
What happens minutes after injury if sustained
The neurone will immediately stop conducting action potentials beyond site of injury
The 2 ends of the cut axon will be exposed and they will start leaking intracellular fluid- axonal transport occurs in both directions
The cut ends will soon pull apart, sealing themselves and swelling at same time
An hour or so after injury is sustained
Synaptic terminal degenerates- accumulation of neurofilaments, vesicles
Astroglia surround terminal normally - they react by causing terminals to be pulled away from postsynaptic cell
Fate of the distal segment of a severed nerve
The segment of the axon distal to site of lesion is never viable
It soon dies as a result of loss of nutritional support from cell body
The axonal segment undergoes Wallerian degeneration
The axon is digested by phagocytes
Tissues that might be preserved are: myelin sheaths, epineurium, perineurium, Endoneurium
These form hollow tubes to guide any new re growth of the end of proximal end
Days to weeks after axotomy
The distal segment stump of axon will undergo Wallerian degeneration (I.e. digested by phagocytes)
Fate of the proximal segment of a severed nerve
Days after sustained injury the proximal segment undergoes chromatolysis
The cell body soon becomes very active producing lots of proteins for repairing cell
The volume of the cell body increases and it also becomes bloated with newly synthesised products
The nucleus of cell is consequently displaced from its central position to peripheral margins of cell body
Then injured nerve soon seals wounded stump to form neuroma
This segment doesn’t die, in some cases the nerve stump soon regenerates to innervate peripheral structures
Fate of the axonal stump on proximal segment of axon
Regenerating axons form many sprouts some of which find Schwann cell tubes
Severing the axon causes degenerative changes in the injured neuron and in the cells that have synaptic connections with injured neuron
Acute phase of denervation muscle that’s not reinnervated
The muscle is immediately paralysed
The muscle will become areflexic
The muscles will start to fasciculate
If muscle is not reinnervated the fasciculations will subside
Muscle will become atonic
Chronic phase of denervation muscle that isn’t reinnervated
As the fasciculations subside the muscle will: lose bulk due to denervation (denervation atrophy), lose bulk due to lack of use (disuse atrophy)
The muscle will die
Muscle tissue will be replaced with connective tissue including fat
This is a state of fibrosis
What is rhabdomyolysis
Potentially life threatening disorder caused by breakdown of skeletal muscle resulting in release of various intracellular contents into circulation
This then leads to acute renal failure and possible death
Causes include: crush syndrome in areas of frequent earthquakes , vehicular accidents at high speed
What is a reflex
Neural reflexes are stereotyped involuntary reactions of CNS to specific sensory input that can trigger any particular reflex
Produce a rapid response
Somatic and autonomic
What is the clinical relevance
Testing reflexes
Papillary reflex and deep tendon reflexes
What are the general function of reflexes
Constantly adjusting level of skeletal muscle contraction
Protective - stop injury and damage, e.g. limb withdrawal, coughing
Postural control- e.g. walking
Homeostasis- autonomic, e.g. blood pressure
What is the reflex arc
Sensory receptor- afferent- integration centre- efferent- effector
Communicates with other parts of nervous system
What are the neural components
sensory receptors
Afferents- sensory neurones
Integration centre: interneurones and modulation
Efferent neurones
Effectors
what do the afferents do
Pass through integration centre, part of CNS, brain or spinal cord, might directly synapse with efferent neurones or synapse in between in centre with neurone that lives in integration centre
What are interneurones
Not called relay neurones
Inbetween sensory and motor neurone
Found in CNS, spinal cord, brainstem nuclei , enteric NS (found in gut)
Take inputs compute them then output
Modulation
Inputs and outputs
Clinical relevance
Can influence reflex arc action through inputs through other parts of CNS through conscious effort
Efferent neurones
Innervate effectors
Motor neurones
Not just in somatic NS also in autonomic
Effectors
Not always skeletal muscle, can be cardiac, smooth or glandular tissue if autonomic reflex
Produce an appropriate response to stimulus
Simple stretch reflexes (myotatic)
Stimulus- stretch skeletal muscle
Changes muscle in response to stretch
Posture
Adjust degree of skeletal muscle contraction
Sensory receptors- proprioceptors
Two main types: muscle spindles and Golgi tendon organs
What are proprioceptors
Found in muscle, joints and tendons
Various points in muscular skeleton
They detect joint position and degree of stretching a muscle
The muscle spindle
Responds to stretch, stretch receptive sensory receptor
Live in skeletal muscle
Receptor-Sensory neurone- direct synapse with efferent (alpha motor neurone)- innervating skeletal muscle
Made up of specialist muscle fibres, sensory axon wraps round, receptors on nerve endings of sensory axon
Monosynaptic reflex arc
How does muscle spindle work
Increase in stretch increases sensory activity (increased AP), releases excitatory neurotransmitter, stimulates AP in motor neuron increasing motor activity, NMJ releases ACh, increases contraction- preventing damage
Knee jerk reflex uses muscle spindles
Stimulus (stretches quadriceps), AP in afferent, sensory neurone splits into branches, one has a direct synapse with motor neurone which causes muscle (quadriceps) to contract, one forms a synapse with interneurone which releases inhibitory neurotransmitter so motor neurone stops firing AP so muscle (hamstring) doesn’t contract
Golgi tendon organ
Sensory receptor for skeletal muscle
Reverse (inverse) myotatic reflex
Sometimes sensory neurones have nerve endings within tendons within collagen fibres of tendons connecting muscles to skeleton
Sensory neurone- inhibitory interneurone within spinal cord- efferent neurone- effector
So if activate GTO through lots of contraction cause muscle activity to decrease
How to Golgi tendon organs work
Increase in contraction of muscle (pulls on tendons)- increases GTO activation as more AP in sensory neurone- releasing excitatory neurotransmitter- excite interneurone to produce AP- release lots inhibitory transmitter- blocking activity in motor neurone
Polysynaptic
Function of reverse myotatic reflex
Prevents damage due to overwork
Fine control of muscle tension
Crossed extensor reflex
Sensory receptors activated- sensory neurone branches many interneurones, some excitatory and some inhibitory, cross spinal cord and synapse with efferents
For each leg one muscle is inhibited from contracting and one stimulated to contract
Function of crossed extensor reflex
Coordinated stereotype response
Coordinating a pair of muscles to be contracted or relaxed
Transfer of weight
Adjusting postural control
Do all reflexes use proprioceptors
No
Withdrawal reflex- pain, burning etc
Why is it important that local anaesthetics are lipid soluble
LA block voltage gated Na+ channels from the inside of neurons, to gain access to the inside of the neuron they must cross the plasma membrane which is made up of phospholipid and therefore need to be lipid soluble
Essential for penetration of both the epineurium and neuronal membrane. The greater the lipid solubility of a drug enhances potency but also enables more rapid diffusion through cell membranes, this hastens the onset for anaesthesia in isolated fibres
How do local anaesthetics work
Local anaesthetic agents are amphipathic molecules
They bind primarily to Na+ channels but also to K+ and Ca2+ channels and GPCRs
Unionised molecules cross neuronal membrane, molecules dissociate to reach new equilibrium of unionised and ionised moieties, dependent on intracellular pH and pKa of anaesthetic. Ionised form binds to open voltage gated Na+ channels in a reversible and concentration dependent manner. Bound molecule stabilises inactivated receptor state preventing further neuronal transmission, nerve block is concentration dependent, increased concentrations inhibit all nerve conduction
Local anaesthetics
Competitive antagonists at nicotinic acetylcholine receptors
Reversibly block nerve conduction when applied to a restricted area of the body to enable a procedure to be carried out without loss of consciousness
Experience of pain reflects damage to the body: detected by nociceptors and converts stimulus into AP
Chemical nature of local anaesthetics
Aromatic ring- lipid soluble to cross membranes
Basic amine group: equilibrium with water, accepting and donating H+
Aromatic ring and amine group attached by either an ester or amide
Ionisation state determined by pH
In body larger proportions are ionised than not
Mechanism of action of local anaesthetics
De-ionised and ionised forms exist outside the cell
Unionised form moves across the membrane into neuron
New equilibrium inside the axon: the ionised form blocks open voltage-gated Na+ channels, as it blocks open channels, it is a use dependent block because increase pain means increased open channels
Tissue pH affects effectiveness of LA.
-inflammation/infection causes more acidic conditions
-increased acidity further increases amount of ionised to unionised
-means LA cant cross membrane ands has weaker affect
Sensory information is divided into 4 categories
Modality
Intensity
Duration
Location
Forms of sensory receptors
They each take stimulus energy and transform into neural info- transduction. Type of transduction specific to type of energy used by given sensory system
Exteroceptors
Interoceptors
Mechanoreceptors -mechanical energy
Photoreceptors- electromagnetic energy
Chemoreceptors- chemical
Thermoreceptors- temperature
Nociceptors- noxious (chemical, thermal, mechanical), somatic sensory, pain.
What is receptor potential
Change in electrical state, a passively conducted change in membrane voltage
Intensity of receptor potential is related to intensity of stimulus
Generator potential
In other systems (mechanical and olfactory) the receptor specialisations are contained on primary sensory neurones
So receptor potential is referred to as generator potential since once the membrane crosses a threshold the neuron generates action potentials
Routes of administration of local anaesthetics
Topical- applied directly to skin or mucus membranes, liquids, creams, gels, sprays, patches
Infiltration- injection into tissue
Nerve block- injected into tissue near major nerve
Injected into epidural space/ subarachnoid space in spinal cord
