NAS Flashcards
Manifestations of lower motor neurone damage
Flaccid muscle weakness
Hypotonia/atonia
Hyporeflexia/areflexia
Denervation muscle atrophy (muscle wasting)
Fasciculations
What do nerves supply?
Skeletal muscle
Smooth muscle
Glands
Caused of degeneration of nerves
Acquired through injury
Genetics of the body
Natural processes of aging
Which nerves regenerate?
Peripheral have the capacity to regenerate and Reinnervate
Central nervous system does not (capacity is there already)
Dysfunction of nerves
Environment damaged or interfered
Severity depends on nature of insult
Structured of neurone
Epineurium
Perineurium
Endoneurieum
Myelin sheath
Axon
(Getting more deep as you go down)
Fascicle
A collection of axons
Seddon’s classifications of nerve injuries
Neuropraxia
Axonotomesis
Neurotmesis
Neuropraxia
Most minimal
Damaged to peripheral aspects
Temporary loss of function
Most probably at level of myelin sheath
Restoration would be complete upon recovery (ie blood supply back to limbs)
Axonotomesis
Damage to axon
Connective tissue tubes remain intact but myelin and axon damaged -> means recovery can attract a new axon to restore function
Result of a severe crush injury to peripheral nerve
Neurotmesis
Fractioning of nerve/completely transected
Most severe
Axon and connective tissue all flanged
No recovery of function occurs
Nerve injury is divided into two parts called..
Proximal segment
Distal segment
Proximal segment will survive?
Yes as closer to cell body and will recurve support
Distal segment will survive?
No
Often cut off
Loses potential repairs
Loss of nutritional support
Becomes vulnerable to phagocytosis by glia, some tissues may be preserved to form hollow tubes
Sends signals of death
wallerian degeneration
3 classes of glial
Myelin forming -> oligodendrocytes, Schwann cells
Astrocytes (create a good environment)
Microglia (immune)
What happens to the axons after injury? minutes
Produce ?injury potentials from proximal
Axons will start leaking intracellular fluid
?neuroma
Sealing and swelling
Synaptic transmission stops
How do microglia react to damaged neurones?
Change from surveillance cells to phagocytes
What happens to synapses after injury?
hours after AstroGlia remove terminals and move away
So lose input and output
Synaptic terminal degenerates accumulation of neurofilaments/vesicles
Chromatolysis
Proximal segments undergoes a few days after injury
Cell body becomes very active -> produce proteins for repair
Swells with new products
Nucleus moves to peripheral
Nerve seals and forms neuroma
Change in colour of cell body
Minutes after injury…
Synaptic transmission cut off
Cut end swells
Denervation
Loss of nerve supply
Re-innervation
Re growth of nerve to re supply
Biochemical structure of muscle
Determined by chemicals released by neurone
Ie will change type of neurone that is connected is different
Acute phases of denervated muscle
Paralysis immediately
Areflexic
Fasciculate
Atonic
If not reinnervated then fasciculations will subside
Disuse atrophy
Loss of muscle due to no use
Chronic phase of denervated muscle
Fasciculation subside -> lose bulk due to lack of innervation
Will die
Muscle replaced with connective tissue including fat
State of fibrosis
Rhabdomyolysis
Life threatening disorder
Breakdown of skeletal muscle
Release of intracellular contents into circulation
Leads to acute renal failure
Possible death
Causes:
Crush syndrome
Vehicular accidents
Injected substances of abuse into muscle
Over exercise
Certain forms of pathologies that can damage muscles
Reflex definition
Stereotyped (predictable)
Involuntary
Rapid
In both somatic and autonomic
Autonomic system
Smooth muscles or glands
Somatic system
Skeletal muscle
Testing reflexes in clinical
Pupillary reflex
Deep tendon reflex
Function of reflexes
Protection (limb withdrawal)
Postural control (eg walking)
Homeostasis (Bp)
Neural components of a reflex arc…
Sensory receptor
Afferent neurones
Somatic: directly though integration or to efferent
Efferent
Effector
Interneurones
-> relay neurones
Take information from various inputs
Found in CNS - spinal cord, brain stem nuclei, and enteric
Part of integration
Can influence integration?
Can modulate by other inputs
Eg your brain can over come something hot etc
Efferent neurones
Bring about response
Inner age effectors
Effectors
Glands/muscle
Appropriate response
Myotatic
Simple stretch reflex
Posture
Adjust degrees of contraction in skeletal muscle
Sensory receptors: proprioreceptors
Proprioreceptors types
Muscle spindle
Golgi tendon organ
Muscle spindle reflex
Found in skeletal muscles
Monosynaptic, no interneurone (Direct afferent efferent connection)
Increased stretch ie lifting weight
Increase sensory/Motor activity -> increase ach
Why is muscle spindle reflex useful?
Why?
Increase contraction so prevent damage
Why is it important that the muscle spindle sensor neurone branches?
Relaxes paired muscle
The branch will then go to interneurone where inhibits motor
Golgi tendon organ
Reverse myotatic reflex
Increase contraction
Increase sensory activity
Interneurone is inhibitory
So will block efferent activity
Muscle activity decrease
What does GTO help?
Prevent damage due to over work
Stops the ripping of muscle
Fine control of muscle tension
Crossed extensor reflex
Pain
Sensory neurone increased activity and branches
Communication with brain -> ouch
Effects motor neurones from many interneurones
Effect:
-lift foot with pair of muscle (contract and relax)
-transfer weight back onto other foot
Connections through spinal cord to other side of body
Electrical excitability
Are able to momentarily discharge the standing electrical potential between the intra and extra compartments
How all living cells establish a resting membrane potential
Selectively concentrating various combinations of species of charge carrying particles within the intracellular compartment
Results in conc differences
Energy differences then give rise to an electrical potential
Use of a cells membrane
Defines the cells boundaries
Encloses the organelles
Enables the cell to create an internal environment that promotes normal functions
Creates an internal environment that is different from outside
A phospholipid is made from…
Phosphate
Glycerol
Fatty acid
What are charge carrying molecules?
Organelle
Proteins
Anions and cations
What is the resting potential of nerve cells?
-65 to -70mv
Relatively negative inside cell
What happens to the resting membrane potential at death?
Discharge permanently
What are excitable tissues?
Nerve
Muscle
And some gland
How to create an intracellular compartment?
Selectively permeable membrane
Some particles can cross (assisted maybe)
Some can’t
Transport ATPases
Presence of ion channels
Non-selective ion channels
What factors effect the movement of a particle across the membrane?
Size
Electrical charge
Whether it’s recognised by transport systems
What are ion channels?
Protein in the membrane
Trans-membrane spanning proteins
Water filled central pore
Facilitate passive movement
Some are selective/some not
Most common ion channel types
Voltage gated
Ligand gates
Mechanically gated
Non-gated
Leak
What are ion pumps?
In cell membrane
maintain rmp
Don’t set up RMP
Some Known as ion-exchange pumps
Without max 10mv difference in RMP so not crucial
What is discharge?
No unequal distribution
No RMP
0mv
Concentration gradients of:
Na+
K+
Cl-
Ca2+
Inside
Low Na+ 15mM
High K+ 150mM
Low Cl- 9mM
Low Ca2+ 10^-7mM
Outside
High Na+
Low K+
High Cl-
High Ca2+
What is a graded depolarisation?
The level that the membrane is depolarised is linked to the strength of the stimulation
Threshold level…
Is the level of membrane potential at which graded depolarisations become an action potential
It’s different in different tissue types
Factors that determine the movement during an action potential
The concentration differences at RMP
depolarisation
When the AP is generated
At rest, what is the movement of ions?
K+ under a conc gradient of them moving outside, however the negative charge prevent diffusion
Na+ large conc outside cell, want to diffuse in
Nernst equation used for?
Calculate the membrane potential at equilibrium for each of ions
Nernst equation is
Eion = RT/zF ln ([outside]/[inside])
R is gas Constant
T is temp in kelvin
Z is valency of ion
F is faradays number
What is the Goldman Hodgkin Katz equation?
Modification of Nernst equation
Takes into account relative permeability of ions
As ion channels can change permeability
How is RMP maintained?
Slow leak of Na+ ions into cell and K+ ions out of the cell
Sodium potassium ATPase maintains ionic conc grad over time
Why is the RMP close to the Ek?
As the membrane is more permeable to potassium
Why is there little cl- movement?
As RMP is very close to E Cl-
Depolarisation steps in AP
Na+ enters cell
Membrane depolarises
To threshold
Na+ channels open (vg)
K+ channels open (vg)
Peak
Inactivates Na+ channels
More vg K+
K+ efflux
Repolarises
What are the basic cell components of the CNS?
Neurones
And glia
What’s soma?
The cell body of a neurone
How is the nervous system organised? 3 ways
Peripheral vs central
Motor vs sensory
Somatic vs autonomic
Structure of neurone?
Cell body
Dendrites
Axon
Synapses
Parts of the CNS are?
Brain
Spinal cord
Three meningeal layers:
Dua mater, pia mater, arachnoid
What does the PNS do?
Connect CNS to target organs
Connects sensory to CNS
CNS integrated information
What does PNS include?
31 spinal nerve pairs
12 cranial nerve pairs
Ganglia
Nerve plexuses
Enteric nervous system
What are ganglia?
Swelling or branches of nerve tissue
What are nerve plexuses?
Networks of nerves carry both afferent and efferent
Brachial/lumbar/sacral
Three main types of neurones
Multipolar (multi to one)
Bipolar (one to one)
Pseudo-unipolar (doesn’t go through cell body)
What are glial cells used for?
Responsible for creating optimum micro environment for neuronal activity
What are the four types of glial cells?
Astrocytes
Microglia
Ependymal
Oligodendrocytes
What shape are astrocytes?
Star dhaped
What are astrocytes used for?
Maintain BBB
Provide structural and metabolic support
Maintain synapses (clear up)
What are microglia used for?
Immune function
So are phagocytic and clear up dead neurones as well as preventing pathogens
What are ependymal cells used for?
synthesis of CSF
What is CSF useful for?
Nutrients
Microenvironment
Protection
Boyancy
What type of cells are ependymal cells?
Simple ciliated epithelial cells
What do oligodendrocytes do?
Create myelin sheaths in CNS
Provide metabolic support
And electrical insulation
What is a glial unit?
One oligodendrocyte wrapped around one part of an axon
What do Schwann cells do?
Great myelin sheaths around PNS neurones
Provide metabolic support and electrical insulation
What is myelination used for?
Increase speed of conduction
Provides protection
Structural support
Do unmyelinated cells still have Schwann cells?
Yes
Still surrounded but no total encapsulation
So are still supported
Propioception what is it?
The awareness of our body in 3d space
What is the afferent part of the nervous system?
Sensory/input portion of NS
stimulus from PNS to CNS
What is the efferent part of the nervous system?
Motor part of the nervous
What types of muscles does the efferent innervate?
Skeletal (somatic)
Autonomic:
Smooth
Cardiac
Bundles of axons are called…
Fascicles
The outer layer of a fascicle is called..
Epineurium
The connective tissue around fascicles are…
Perineurium
What connective tissues surround individual axons?
Endoneurium
What are the basic cell components of the PNS?
Neurones
Schwanna cells
Satellite cells
What does the body of the neurone contain?
Nissl substance
Cytoskeleton
What does nissl substance contain?
Aggregates of polyribosomes and RER
What does cytoskeleton contain?
Neurofilaments
Neurotubules
Functions of satellite cells
Electrically insulates PNS
regulates nutrients and waste exchange for cell bodies in ganglia
What shape are ependymal cells?
Cuboidal
Some areas they are ciliated
Lack basal lamina
Where are ependymal cells found?
Like Brain
spinal cord central canal
How many legs or wraps can oligodendrocytes do?
Multiple
More than one
What are the types of Astrocytes?
Protoplasmic
Fibrous
Where are protoplasmic astrocytes found?
Grey matter
Where are fibrous astrocytes found?
White matter
What is an electrical synapse?
Rare in adults
Bidirectional
Fastest
Adjacent cells
Direct transfer of ionic current
What are the major types of neurotransmitters?
Amino acids
Monoamines
Neuroactive peptides
Neurotransmitter receptors mechanisms
Membrane spanning proteins
Transmitter binding causes conformational change
Specific to neurotransmitter
One neurotransmitter can have several receptors
What are the two types of signalling mechanisms for receptors?
Ionotropic (conformational change)
Metabotropic (g protein- indirect effects)
Spatial summation is
Summing of post synaptic potentials generated at separate synapses to the same cell body
Temporal summation is…
Summing of post synaptic potentials generated at the same synapse
Define the term motor unit
The nerve and the muscle fibres it supplies
It is the somatic efferent and all the muscles fibres it supplies
A-motoneurone
And all extrafusal muscle fibres
What are the different types of motor unit?
Slow twitch (s)
Intermediate (fr)
Fast (ff)
What are the components of a Motor unit?
Motor neurone
Skeletal muscle
Neuromuscular junction
The three connective tissues in muscle fibres
Epimysium
Perimysium
Endomysium
Different types of muscle fascicles based on their architecture
Convergent
Strap
Circular
Fusiform
Pennated (uni, bi and multi)
Where are lower motor neurone found?
Cranial nerves
Lamina ix
All muscle fibres in a motor unit have…
The same contraction speeds
Susceptibility to fatigue
Myosin fibre typing
What’s the membrane of a muscle cells in a nmj called?
Sarcolemma
What are the receptors in the folds of the sarcolemma?
Nicotinic ach receptors at top
Voltage gated sodium channels at bottom
Steps of release of acetylcholine
High conc of ca2+ outside neurone
Action potential reaches pre synaptic terminal
Depolarisation Causes vg ca2+ channels to open
Synaptotagmin changes conformation as ca2+ binds
Triggers vesicle fusion and realise via exocytosis
What is special about a NMJ?
Multi quanta release- way way more vesicles per synapse
Junctions fold in postsynaptic
What happens when ach binds to NMJ?
Binds to Nicotinic ach receptor
Channels open
That are permeable to na+ and k+
Down conc and electrical gradient
Na+ influx, less k+
Produces an end plate potential
What does an end plate potential trigger?
An action potential in muscle
V-g ion channels to open
Why does a muscle always contract
Lots of vesicles
Lots of nachrs
So produces a EPP that is very large
So easy reach threshold
What is a t tubule for?
Allows ap to transmit deep into muscle fibre
What is the job of a DHP receptor?
When an action potential reaches it, it allows Ca2+ into muscle
This then causes Ryanodine receptor in SR to release ca2+
What is a DHP receptor?
Dihydropyridine l type ca2+ voltage-gated channel
What is acetyl choline broke down by?
Acetyl choline esterase
What is myesthenia gravis cause by?
Autoimmune
Reduced number of nAChR in NMJ
What is syncytium
Many nuclei within one muscle fibre as cells are fused
Structure of skeletal muscle
Parallel regular
Single units
No branches
Nuclei at periphery
Structure of cardiac muscle
Striations less obvious
As branched
Nuclei in middle
Intercalated discs- where cells meet
Structure of smooth muscle
Single cells
With one nucleus
Spindle shaped
No striations
Not distinct
What is a sarcomere?
Contractile unit
A band has…
all of the myosin
H zone is…
Purely myosin
I band is…
Purely the actin
What are the three major types of skeletal muscle?
Red fibres (i)
Intermediate red (iia)
White (iib)
Triads vs Diads?
What muscles type are t tubules present?
Striated only
What is a myofilament?
The actin and myosin
What is a myofibril?
Chain of sarcomeres
Actin-myosin cross bridge steps
Attachment of ATP
Bending of myosin head
Due to energy of hydrolysis of ATP
attached to actin to form a bridge
The release of phosphate allows to return to normal
New ATP bonds and releases actin
The binding of ca2+ to troponin causes…
The exposure of tropomyosin
Triads have what components?
A t tubule next to two sarcoplasmic recticulums
Terminal cisternae is part of what organelle?
Sarcoplasmic reticulum in muscle
Next to t tubules
Calsequestrin holds what in the SR lumen?
Ca2+
Why are red fibres red?
High levels of myoglobin
To fully use o2
What shape are intercalated discs in cardiac muscle?
Irregular lines
Local anaesthetics key points
Reversibly block
Without loss of consciousness
What type of receptor does local anaesthetics block?
Nociception (pain)
Block voltage gated sodium channels
Name ending of local anaesthetic
-caine
What are the components of local anaesthetics?
Aromatic ring (hydrophobic)
Linkage group (amine or ester)
Basic amine group (water soluble)
What pH is the local anaesthetics?
Weak base
If normal pH is more alkaline, then which part of the equilibrium is favoured?
More dissociation
More ions
What part of the local anaesthetic can diffuse across the membrane?
Only the whole version
Not ion
Which part can block the receptor of a local anaesthetic?
The charged
But only from the inside
What factors effect the local anaesthetics effectiveness?
Tissue pH
-from inflammation or infection
Size of neurone
Routes of administration
What are the 6 routes of administration of local anaesthetic?
Topical
Infiltration
Nerve block
Epidural
Spinal
Regional
What are the side effects of local anaesthetics?
Hypersensitivity
Affect on other excitable tissues
-heart attack
-blood vessels etc
Why are vasoconstrictor given with local anaesthetics?
Promotes blood vessels constricting
Reduce unwanted effects
Increase duration, as not dispersed into blood as much so doesn’t reach liver
What are the 3 sources of dysfunction in a motor system?
Lower motor neurone
Upper motor neurone
Muscle
Re-innervation is the…
Realignment of nerve with an organ different to its original one
Loss or damage to cell body of a motor neurone would lead to…
Death of the motoneuron
Diseases that target cell bodies of neurones
Polio myelitis
-caused by polio virus
-cell bodies in the central horn
What are the two variants of motoneurone disease?
Kills both upper and lower
Or
Only the lower motoneurone
Which motoneurones are not susceptible to MD?
Ones that supply extraocular muscles
Supply Anal sphincter
Demyelination of axons could be a result of what diseases…
Guillain-barre
Diabetes neuropathy
Lower motor neurone symptoms
Paralysis
Fibrillations
Fasciculation
