Flashcards in Neuroscience and Mental Health Deck (363):
The nervous system is divided (2)
Central Nervous System
Peripheral Nervous System
Ganglia (clusters of neuronal cell bodies)
PNS functionally divided into (2)
Somatic (motor and sensory divisions)
Autonomic (motor and sensory divisions)
What is the Somatic PNS?
Controls motor and sensory function for the body wall e.g. skin (sensory neurone) and skeletal muscles (motor neurone)
What is the Autonomic NS?
Visceral PNS, vegetative NS, involuntary NS
Regulates function of the viscera (internal organs, smooth involuntary muscle, pupils, sweating, blood vessels, bladder, intestine, glands etc.)
Controls heart contraction rate
Has sympathetic and parasympathetic arms
The type of nerves in the sympathetic division of the ANS are...
The type of nerves in the parasympathetic division of the ANS are...
The type of nerves in Somatic NS are...
Brain is composed of (3)
Cerebral cortex (cerebrum)
Describe the input/output to cerebral cortex
Each receives sensory info and controls movement of opposite side of the body
What is the function of the cerebellum?
Controls motor coordination (movement) and involved in learning motor skills
Describe the brainstem
Most primitive part
Densely packed fibres
Regulates vital functions (e.g. consciousness, breathing)
Damage here usually serious (can be fatal)
What are the dorsal and ventral roots of the spinal cord?
Dorsal and ventral roots that emerge from the SC
Are part of the PNS
Describe the overall process of neurotransmission (not ions just overall action of NTs)
An AP reaches a neuronal chemical synapse
NTs released by presynaptic terminal bind to post-synaptic receptors
What are the differences between the regenerative capacities of injured axons in the CNS and PNS?
Unable to regenerate over long enough distances to be useful
Axons in PNS can regenerate after injury
No inhibitory molecules
How is regeneration/recovery compromised in the NS?
Recovery compromised by non-specific target re-innervation and aberrant axon sprouting
Absence of guidance cues to stimulate axon growth during development
Define: Afferent axons
Axons entering CNS
Propagate APs towards brain and spinal cord from PNS
E.g. sensory neurons (somatic and ANS)
Define: Efferent axons
Axons leaving CNS
Propagate APs from brain and spinal cord to PNS
E.g. motor neurons (somatic and ANS)
CNS neurones that synapse with other CNS neurones within brain or spinal cord
What do somatic sensory neurons convey?
Convey sensory info from body to SC and then there to sensory cortex
Stimulate reflex activity
Where is sensation perceived?
Are the sensory and motor cortex anatomically distinct?
What does white matter comprise of?
Ascending and descending axon tracts to/from the brain
What are needed for a reflex response?
Somatic sensory inputs-> (interneurons)-> motor outputs from SC
Neurones must be intact
NOT communication with sensorimotor cortex
What is required for conscious registering of a sensory stimulus?
Sensory inputs activate sensory neurones in grey matter of SC (ascending tracts-> sensory cortex of the brain)
What happens to neurones from the motor cortex?
Axons extend downward to synapse with spinal motor neurones and transmit APs (descending tracts)
Important for voluntary movement
Lost voluntary movement and sensation in L arm
Muscles show reflex activity
Likely to be injury to R hemisphere
Close to sensorimotor cortex
Not peripheral nerve (reflex intact)
Not SC (only 1 arm)
Lost voluntary movement and sensation in L arm
Muscles don't show reflex activity
Likely to involve periphery (lose reflex)
Not SC (only 1 arm)
Probably due to fall
Lost voluntary movement in L arm and leg
Muscles show reflex activity
Likely to be in R brain sensorimotor cortex (leg and arm region)
Not peripheral (reflex intact)
Not SC (only 1 side)
Probably brain tumour? Stroke?
What is neurology?
Study of brain, SC, peripheral nerves and muscle
What components are there in a standard neurological exam?
Gait and station
MMSE (mini mental state exam) categories
Attention and calculation
Year, season, date, day, month
Country, city, part of city, house no., street name
3 objects said by Dr
Repeated until patient remembers all 3
Count trials and record
MMSE: Trials- attention and calculation
Serial 7s- 1 point for each correct
Stop after 5
Spell 'world' backwards
MMSE: Trials- Recall
Ask for 3 objects in registration phase
MMSE: Trials- Language
Name certain items, repeat certain phrases, follow 3 stage command etc.
5 stages of diagnosing neurological problems
Approach (present signs and symptoms to ID underlying anatomy-> characterise syndrome)
History (nature/onset of symptoms, family/social history, prev. medical problems)
Examination (MMSE, nerves, limbs)
Investigation (scans, lumbar puncture, EMG, EEG, pathology)
What does an EEG do?
Measures electrical potentials at scalp generated by underlying neurones
Useful for diagnosing epilepsy and coma
What are EMG and NCS used for?
Electromyography and nerve conduction studies
Examines integrity of muscle, peripheral nerve and lower motor neurones
How are CTs used in neurological diagnosis?
Uses X-ray source, high conc. of ionising radiation
Shows hard tissues well
Relatively fast and inexpensive
How are MRIs used in neurological diagnosis?
Based on behaviour of H protons in the tissues to a strong, externally applied magnetic field
Good for differentiating soft tissues
Don't use ionising radiation
What do lumbar punctures study and where can it be obtained from?
Between L3 and L4 AND L4 and L5
What can be used for neurological diagnosis?
Neurophysiology= EEG, EMG, NCS
Imaging= CT, MRI
What causes a stroke?
80% blockage of blood vessel (infarct- which may be caused by carotid arteries in neck)
20% bleeding (haemorrhage often related to high BP)
Where can strokes affect?
Any part of the brain (including brainstem)
Tends to cause problems contralateral to brain lesion
Symptoms relate to which artery in brain is affected
What are stroke risk factors?
Why can strokes cause aphasia?
Left side of brain responsible for language
Strokes here can lead to aphasia
Where do strokes most commonly affect and what symptoms does it cause?
Middle cerebral artery
Results in weakness and loss of sensation on the other side
What are the symptoms of posterior cerebral artery strokes?
Affect occipital lobe
Result in visual loss on contralateral side
What are the symptoms of anterior cerebral artery strokes?
Often cause contralateral leg weakness
What are the symptoms of strokes affecting the brainstem?
Problems with balance
Speech and swallowing
Stroke treatment: Acute
Intravenous thrombolysis- dissolve clot
Intra-arterial thrombectomy- remove clot
Stroke treatment: Complications
Neurosurgery for haemorrhage or dangerously high pressure
Stroke treatment: Prevent further stroke
Thin blood with aspirin
Treat diabetes and high cholesterol
Treat dangerously narrow carotid arteries
What neurotransmitter is associated with Parkinson's disease?
What are PD patients treated with? And why not Dopamine?
Dopamine doesn't cross BBB but levodopa crosses BBB and then converted into dopamine
Also treated with deep brain stimulation (DBS)
What are the causes of Spastic Parapesis?
Inflam/autoimmune (e.g. MS)
Neoplastic (e.g. SC tumour)
Degenerative (e.g. motor neurone disease)
Vitamin deficiency (b12)
Infection (e.g. syphilis)
Vascular (anterior spinal artery thrombosis)
---> sensory level
What is Multiple Myeloma?
Tumour of plasma cells
Treated with radiotherapy and chemotherapy
What causes Acute Polyneuropathy?
Infections e.g. Diptheria
Autoimmune e.g. Guillain Barre
Drugs e.g. chemo
Exposure to toxins e.g. organophosphate insecticides
What is GBS/AIDP?
Common cause of acute neuromuscular weakness
Progressive ascending sensorimotor paralysis with areflexia, affecting 1 or more limbs and reaching nadir within 4 weeks
Patients may progress to almost complete paralysis and require ventilation
What is the treatment for GBS/AIDP?
Immunotherapy= plasma exchange or IV immunoglobulin
Supportive e.g. ventilation
Anticoagulation to prevent leg clots (and subsequent pulmonary emboli)
What are the symptoms of Parkinsonism?
Soft, monotonous speech
Slow shuffling gait
Loss of arm swing
Increased tone and cogwheeling
Micrographia (small handwriting)
What is a neurone?
Basic structural and functional unit of the NS
Responsible for generating/conducting electrical signals
Supported by neuroglia
Highly organise metabolically active secretory cell
What is the ratio neuroglia:neurones
Describe neuronal structure
Cellular structure of all neurones is similar (diversity achieved by differences in number and shape of their processes)
Well developed Golgi
Highly organised cytoskeleton
What is a dendrite (input)?
Dendritic spines receive majority of synapses/info
Spread from cell body
Increase s.a. of neurone
Often covered in spines (protrusions)
NB. Large pyramidal neurones may have 30,000-40,000 spines (pyramidal cell body in pyramidal cells)
What is an axon (output)?
Conduct impulses away from cell body
Emerge at axon hillock
Usually 1 per cell (may branch)
Contain abundant intermediate filaments and microtubules
Can be myelinated or unmyelinated
Organised into (molecular) domains
What are the domains in an axon?
What is an axon terminal?
Axons often branch extensively close to target (terminal arbor)
From synaptic terminals with target
Either bouton (synapse) or varicosities (in smooth muscle cells)
What are synapses?
Contain synaptic vesicles containing neurotransmitters
Vesicles fuse with axon membrane and release NT which reacts with synaptic vesicles
Specialised mechanisms for association of synaptic vesicles with the plasma membrane
Abundant mitochondria needed for ion pumping and synaptic transmission
Neurones can be excitatory, inhibitory or modulatory. Which types are which?
Axo-dendritic= often excitatory
Axo-somatic= often inhibitory
Axo-axonic= often modulatory
Neurofilaments play a critical role in what (to do with neuronal cytoskeleton)?
Name the main intracellular transport types (functional polarization)?
Fast axonal transport
What is fast axonal transport?
Transport of membrane associated materials
Vesicles with associated molecular motors (moved down axon at 100-400mm per day)
Different membrane structures targeted to different compartments
What is anterograde transport?
Transport of materials needed for neurotransmission and survival away from cell body
Fast or slow
Fast= synaptic vesicles, transmitters, mitochondria
Uses microtubular network and requires oxidative metabolism
Slow= bulk of cytoplasmic flow of soluble constituents
What is retrograde transport?
Fast= return of organelles
Transport of substances from EC space
Uses different molecular motors
E.g. Trophic growth factors, neurotrophic viruses
What is the size range of cell bodies?
5 micrometers to 135 micrometers
Describe DRG sensory neurones
2 fused axonal processes
No dendrites (receive no synapses)
Have a soma
Describe bipolar neurones?
Two axonal processes with central soma
E.g. in cerebral cortex, retina
Describe Golgi Type I Multipolar cells
Highly branched dendritic trees
Axons extend long distances
E.g. pyramidal cells of cerebral cortex, purkinje cells of cerebellum, anterior horn cells of spinal cord, retinal ganglion cells
Describe Golgi Type II Multipolar cells
Highly branched dendritic trees
Short axons terminating quite close to the cell body of origin
E.g. stellate cells of cerebral cortex and cerebellum
Describe pyramidal cells of the cerebral cortex
Golgi Type I multipolar
Major excitatory neurones
Single axon with triangular shaped soma
Large apical dendrite which arises from apex of principle cell's soma
Basal dendritic tree consists of 3-5 primary dendrites (profuse branching)
Describe stellate cells of the cerebral cortex and cerebellum
Golgi Type II multipolar
Major excitatory input to cortical pyramidal cells
Small multipolar cells with local dendritic and axonal arborizations
Use glutamate or aspartate as a NT
What are the functional subtypes of neurones?
Sensory (generally pseudounipolar-> 1 to CNS, 1 to sensory receptor)
E.g. DRG neurones
Motor (generally multipolar with large soma)
E.g. spinal motor neurones
Interneurons (can be multipolar or small bipolar local circuit neurons)
What are the functional organisational groups of neurones?
Functional organisation: describe nucleus
Group of unencapsulated neuronal cell bodies within the CNS
Usually consist of functionally similar cells
E.g. Raphe nuclei
Functional organisation: describe laminae
Layers of neurones of similar type and function
E.g. cerebral cortex grey matter
Functional organisation: describe ganglion
Group of encapsulated neuronal cell bodies within the PNS
Functional organisation: describe fibre tracts
Groups or bundles of axons in the CNS
Mixture of myelinated and unmyelinated
E.g. corpus callosum, internal capsule
Functional organisation: describe nerves
Discrete bundles of axons
Bring info to CNS and to effector organs
Often mixed sensory and motor neurones
Usually part of PNS
Describe the role of neuroglia
Support cells of the nervous system
Astroglia, oligodendroglia, microglia, immature progenitors, ependymal cells, Schwann cells, satellite glia
Many and varied functions
Essential for the correct functioning of neurones
Multi-processed star-like shape
Most numerous cell type
Numerous intermediate filament bundles in cytoplasm of fibrous astroglia
Gap junctions suggest astroglia-astroglia signalling
Describe the functions of astroglia
Scaffold for neuronal migration and axon growth
Formation of BBB
Transport of substances from blood to neurones
Segregation of neuronal processes
Removal of neurotransmitters
Synthesis of neurotrophic factors
Neuronal-glia and glial neuronal signalling
Potassium ion buffering
Glial scar formation
What are oligodendroglia?
Myelin forming cells of the CNS
(Interfasicular oligodendroglia and perineuronal oligodendroglia)
Small spherical nuclei
Few thin processes
Prominent ER and Golgi
Metabolically highly active
What are the functions of oligodendroglia?
Produce/maintain myelin sheath
Each cell produces multiple sheaths (1-40)
What is myelin?
Lipid rich insulating membrane up to 50 lamellae
Dark and light bands at EM level
Loss of oligodendroglia and myelin has disastrous consequences
What diseases are caused by faulty myelin?
What are microglia?
Derived from bone marrow during early development
Resident macrophage population of the CNS
Involved in immune surveillance
Present antigens to invading immune cells
First cells to react to infection or damage
Role in tissue remodelling
Phagocytic when diseased (in inflammation)
What are peripheral glia?
Myelin producing cells of the PNS
Each Schwann cell produces only 1 myelin sheath
Surround unmyelinated axons
Promote axon regeneration
Define Multiple Sclerosis
A chronic inflammatory multifocal demyelinating disease of CNS of unknown cause
-> Loss of myelin and oligodendroglial and axonal pathology
Typically affects young adults
Exacerbating-remitting pattern or chronic progessive evolution
Need 2 or more clinical attacks= dissemination in time and space
Symptoms of MS
Visual e.g. double vision
Motor (evenutal paralysiss)
Cognitive and psychiatric
Onset= hours to days
Recovery= days to months
How do you diagnose MS?
MRI (hyperintense white spot signals)
CSF analysis (increased immunoglobulin production)
-> Oligoclonal bands by electrophoresis (has to be matched with blood)
What are the clinical subtypes of MS?
Relapsing-remitting (complete or incomplete recovery relapses)
Secondary progressive (relapses with increased worsening of disability and recovery)
Primary progressive (increased disability with no recovery)
Epidemiology of MS
20-40 years old
More frequently in females
What therapy is used for MS?
Immuno-modulatory and immuno-suppressive treatments are aimed at reducing relapses
Steroids given to patient for his attacks
Treatments to attenuate symptoms (pain, spasticity, bladder dysfunction)
Define: flux (relevant to diffusion)
Rate of transfer of molecules
E.g. no. of molecules that cross a unit area per unit of time (m2/s)
No net flux at dynamic equilibrium
What are the properties of ions?
Opposite charges attract
Like charges repel
Units of electrical properties
Voltage (pd)= volts (ions produce a charge gdt)
Current= amps (movement of ions due to pd)
Resistance= ohms (barrier that prevents movement of ions)
How do you measure membrane potential?
Reference electrode placed outside cell (0V level)
Another electrode inside cell
Measures voltage difference (-ve compared with outside)
All cells have a membrane potential
Describe ion channels
Permeable pores in membrane that open and close depending on trans-membrane V, ligands or mechanical forces
Can be selective for different types of ion
Allows membrane to selectively allow ions to cross
Define electrochemical equilibrium
For an ion reached when its concentration gradient is balanced by the electrical gradient across the membrane
What is the Nernst equation and what does it show?
Equilibrium potential of X ion (mV)
R= gas constant
T= temp (Kelvin)
F= Faraday's number (coulombs of charge per mol of ion)
Ln= natural log
Recall typical concentrations for ions (IC and EC)
.....ION..... EC..... IC.....
Na 150mM 10mM
K 5mM 150mM
Ca 2mM 0.0001mM
Cl 110mM 5mM
Organic phosphates 3mM 130mM
pH 7.4mM 7.1mM
Osmolarity 285mosmol/l (EC+IC)
What is the equilibrium potential for K+?
What is the equilibrium potential for Na+?
What is the typical Em?
Membrane more permeable to K
Why is the membrane closer to K+ equilibrium potential?
K diffuses out of cell (through permanently open channels)
Inside of cell becomes negative
Membrane slightly permeable to Na which cancels out equivalent number of K ions
This means real membrane potential more +ve than K equilibrium potential
K leaky channels
What is the Goldman Hodgkin Katz equation?
Describes the real resting membrane potential
Influenced by Na, K and Cl
Size of each ions' conc is proportional to how permeable the membrane is to the ion
What do different values for P (permeability/channel open probability) mean?
0= 100% closed
1= 100% open
0.5= open 50% of time
Work out mV for....
All channels open all the time
Only K channels open (Cl and Na closed)
K channels open, Na permeability 5% and Cl closed
Which membrane potential tends towards 0 (away from RMP)?
Which membrane potential tends above zero towards Na equilibrium potential?
Which membrane potential tends away from RMP but in same direction as repolarisation (leads to membrane potential closer to K equilibrium potential)?
Which membrane potential tends towards the RMP?
What are graded potentials?
Change in membrane potential in response to stimulation and occur at synapses and sensory receptors
Defining characteristics of graded potentials?
May be depolarising or hyperpolarising depending on stimulus
Magnitude of membrane potential dependent on strength of stimulus and decreases over time/distance from stimulus site
What is decremental spread? (Regarding graded potentials)
Magnitude of membrane potential change decreases with time and with distance from stimulus site
What effect does temperature change have of equilibrium potential of an ion?
Increased temp-> increased permeability-> membrane leaky
What are regenerative capacities?
CNS axons don't spontaneously regenerate after injury in adult mammals
PNS axons readily regenerate, allowing recovery of function after peripheral nerve damage
What are action potentials?
Occur in excitable cells
Nerve impulses that allow transmission of info reliably and quickly over long distances
Important in cell-to-cell communication and can be used to activate IC processes
What cells are electrically excitable?
Critical level to which a membrane potential must be depolarized to initiate an AP
Necessary to regulate and propagate signalling in both CNS and PNS
Define: Refractory state
Period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation
Define: All or nothing
Once triggered, a full sized AP occurs
Define: Saltatory conduction
Propagation of APs along myelinated axons from one node of Ranvier to next node, increasing conduction velocity of APs
Define: Voltage-gated ion channels
Transmembrane ion channels activated by changes in electrical membrane potential near the channel e.g. for Na and K
Define: Channel inactivation
Conformational change of a channel protein by which the channel goes from the open
State to permeate the channel pore
Occurs in sodium channels in APs
Define: Positive feedback
Enhancing or amplification of an effect by its own influence on the process which gives rise to it
Occurs in Na channels in AP
Sequence of events in typical AP
What causes the upstroke in an AP?
VGSCs open quickly
Increased permeability to Na
Na enter cell down electrochemical gradient
VGPCs open slowly
Slightly increased permeability to K
K leave cell down electrochemical gradient
Less than Na entering
Membrane potential moves toward Na equilibrium potential
What causes repolarization in an AP?
Decreased permeability to Na
Na entry stops
More VGPCs open and remain open Increased permeability to K
K leaves cell down the electrochemical gradient
Membrane potential moves toward K equilibrium
What is the absolute refractory period?
Inactivation gate is closed
New AP can't be triggered even with very strong stimulus
What causes hyperpolarization in an AP?
At rest, VGPCs are still open
K continues to leave cell down electrochemical gradient
Membrane potential moves closer to the K equilibrium
Some VGPCs then close
Membrane potential returns to the resting potential
What is the relative refractory period?
Na inactivation gate open
Stronger than normal stimulus required to trigger an AP
Are changes in membrane potential during APs due to ion pumps?
Ion pumps are not directly involved in ion movements during AP, involves passive movement
Electrochemical equilibrium is restored following the AP by K and Na ions moving through non VG ion channels
Some ions exchanged through pumps (but relatively slow)
How long do APs last?
Describe the regenerative relationship between Na permeability and membrane potential
Once threshold is reached, cycle continues
Positive feedback behaviour
Cycle continues until VGSCs inactivate (closed and V-insensitive)
Depolarisation doesn't lead to opening of Na channels
Membrane remains in a refractory (unresponsiveness) state until the VGSCs recover from inactivation
How does passive propagation/transmission/conduction of AP along the axon occur?
Local current flow depolarizes adjacent region toward threshold (becomes new active area)
Active area at peak of AP
Area 'behind' AP is at RMP (old active region)
What is the velocity of APs?
Large diameter, myelinated axons= 120m/s
Small diameter, non-myelinated axons=1m/s
What affects conduction velocity?
Axon diameter (less resistance to current flow inside large diameter axons)
Myelination (faster in myelinated than non-myelinated axons of same diameter)
Cold, anoxia, compression and some drugs (slows velocity)
Name 2 pathological conditions affecting conduction velocity
What does the brain develop from (and into how many divisions)?
From neural tube
3 main divisions= forebrain, midbrain, hindbrain
What divides the 2 hemispheres?
Mid-saggital line (with diencephalon sitting between the 2 heminspheres)
What cover the hemispheres?
Cerebral cortex with gyri and sulci
What is the groove between 2 hemispheres?
Deep longitudinal fissure
What is the forebrain comprised of?
What is the hindbrain comprised of?
What part of the spinal cord has a sensory function and which has a motor function?
Dorsal horns= sensory, grey matter
Ventral horns= motor, grey matter
What is the brainstem?
Describe the dorsal and ventral horns of the spinal cord (cross-section)
Grey matter 'butterfly' with DH (sensory) and VH (motor)
Dorsal root (has DRG)
Roots-> spinal nerve
What spinal segments are higher than their corresponding vertebrae?
Lumbar and sacral
Describe the sensory input pathway in spinal cord
Dorsal root ganglia and dorsal roots
Dorsal horn of GM in SC
Describe the motor output pathway in spinal cord
Ventral horn of GM in SC
What protects the spinal cord?
Segmented structure= vertical column
What does the vertebral column consist of?
Vertebrae surrounding SC
Separated by cartilage rings (shock absorbers)
Intervertebral foramina (gaps between the arches laterally allows spinal nerves to emerge horizontally)
How many spinal nerves are associated with vertebrae?
What are the types of vertebrae?
Cervical (7, 8 nerves above and below vertebrae)
Thoracic (12, 12 nerves below vertebrae)
Lumbar (5, 5 nerves below vertebrae)
Sacral (5, 5 nerves below vertebrae)
Coccyx (2, may be fused to form one bone)
Coccygeal (1 nerve associated)
What is longer, the spinal cord or the vertebral column?
This means spinal and vertebral levels are not level (note for lumbar puncture- to protect SC, below L2, ideally L3-4)
What does the PNS consist of?
Peripheral nerves (axons)
What are peripheral nerves subdivided into?
What are ganglia in the brain called?
Describe sensory neurones (autonomic and somatic) in the PNS
Autonomic and somatic neurones are the same
Receptors on skin, joints, viscera, stimulation triggers AP
Impulses travel via DRG to the CNS (from motor neurones)
Describe autonomic neurones (general) in the PNS
Preganglionic neurone in CNS
Impulse passes along axon, where it synapses at the autonomic ganglion with the postganglionic neurone
Postganglionic neurone then carries impulse to appropriate target e.g. blood vessels, smooth muscle, glands, viscera
Describe autonomic sensory neurones in the PNS
Impulses travel from body periphery via DRG into DH of GM in SC
Describe autonomic motor neurones in the PNS
Preganglionic neurone forms ventral root from VM (of GM) and synapses with postganglionic neurone at autonomic ganglion
Synapse may be close to or far away from SC
Describe somatic (general) neurones in the PNS
Soma in CNS
Impulses pass along ventral root through spinal nerve to appropriate skeletal muscle and trigger contraction
Describe somatic sensory neurones in the PNS
Impulses travel from periphery of body via DRG into the DH of GM within the SC
Describe somatic motor neurones in the PNS
Impulses travel from the VH of GM via the ventral root
The location where dorsal and ventral roots meet WM of SC is the interface between the PNS and CNS
Spinal nerve formed at intervertebral foramen by junction of dorsal and ventral roots
Describe the development of spinal cord and how it relates to GM and WM
SC develops from neural tube, surrounded by GM and WM
GM divided into DH and VH
Dorsal and ventral roots of the somatic NS come together to form a spinal nerve which emerges horizontally from the vertebral column
Describe glia (microscopic organisation)
Sensory neurone cell bodies (both somatic and autonomic) lie in ganglia associated with DRG or some cranial nerves
DRG have no dendrites and are pseudounipolar cells
Postganglionic neurone cell bodies lie in autonomic ganglia (paravertebral sympathetic rows or parasympathetic internal organs)
Supporting cells of ganglia are satellite cells (a type of glial cells)
Describe bundles of axons in PNS
Bundles of individual axons are known as fascicles (fascicles are bundled into nerves)
Blood vessels lie between nerves
Axons are carefully packaged (not damaged by movement)
What are the layers of connective tissue around the myelin sheath of each myelinated nerve fibre?
What is the endoneurium?
Individual axons and their associated Schwann cells are surrounded by delicate loose connective tissue
What is the perineurium?
Groups of axons (fascicle) surrounded by dense connective tissue
What is the epineurium?
Whole nerve surrounded by loose connective tissue
What factors affect conduction velocity of peripheral axons?
Unmyelinated= usually small (1um)
Clothed in cytoplasm of Schwann cells (neurolemma) which can accomodate several axons per Schwann cell
Slow conduction speed= 1ms
Clothed in succession of Schwann cells (each wrapping tightly around the axon in up to 100 layers)
Describe how the myelin sheath is present in the PNS
Wrapping forces the Schwann cells to lose their cytoplasm forming a sheath of cell membranes
Myelin sheath separated by nodes of Ranvier
Increases velocity of conduction via saltatory conduction
Are there Na channels in Schwann cells?
Depolarisation can't occur
Cells therefore act as electrical insulators
Why are myelinated axons more energy efficient?
Repolarisation of membrane requires energy using the Na/K ATP pump
Myelinated axons are more energy efficient as repolarisation occurs at adjacent nodes (not entire axon membrane)
Give an example of the fastest and slowest axon group
Fastest= muscle spindle primary afferent (120m/sec)
Slowest= C-pain fibre (1m/sec)
Area of skin that a single nerve innervates
Striped appearance when drawn out (due to horizontal emergence of spinal nerves from the vertebral column)
Spinal nerves coded by letter and number
Some overlap of innervation (so may not have observable effects if damage to particular spinal nerve)
Group of muscles that a single spinal nerve root innervates
A branch connecting two nerves or arteries
DORSAL RAMI= innervate muscle and skin of back
VENTRAL RAMI= innervate muscles and skin of rest of body
What do the rami communicants (WM and GM) provide?
Interconnections between some spinal nerves and ganglia of the sympathetic NS
Define: Plexus (and brachial plexus/lumbosacral plexus)
Branching network of intersecting nerves
Brachial plexus= ventral rami of spinal nerves C5-T1
Lumbosacral plexus= ventral rami of L2-S2
Describe how spinal nerves are arranged in the main trunk and how they innervate limbs
Main trunk of the body= spinal nerves are in parallel e.g. cutaneous innervation of arm by spinal nerves
To innervate the limbs= combine to form peripheral nerves at plexus e.g. cutaneous innervation of arm by peripheral nerves (looks patchy)
What are peripheral neuropathies?
Result from progressive degeneration of nerves
Causes= metabolic, infections, heriditary
Usually distal to proximal
Affect sensory and/or motor neurons
May affect myelin or axon initially
How can you detect whether a neuropathy is present (if demyelinating or axonal)
How can you study pathogenesis of a neuropathic disease?
E.g. sural nerve to study pathogenesis of the disease
Define: Neuromuscular junction
Specialized structure between a motor neurone and muscle fibre
Includes presynaptic nerve terminal, synaptic cleft, postsynaptic endplate region on the muscle fibre
Allows for the unidirectional chemical communication between peripheral nerve and muscle
What are the typical contact ratio of synapses in the muscle and CNS
1:1 for muscle
1000:1 in the CNS
Outline the 7 step process to initiate muscle contraction (at the NMJ)
1. AP opens VGCCs
2. Ca2+ enters
3. Ca2+ triggers exocytosis of vesicles (vesicle first fuses to terminal)
4. ACh diffuses in cleft
5. ACh binds to postsynaptic receptor-cation channel and opens channel
6. Local currents flow from depolarized region and adjacent region; AP triggered and spreads along surface membrane
7. ACh broken down by acetylcholine esterase (enzyme)
Muscle fibre response to that molecule of ACh ceases
What causes miniature end-plate potentials? (mEPPs)
Individual vesicles releasing ACh at a very low rate
What are myofibres?
Multi-nucleated single muscle cell
Covered by sarcolemma (surface membrane)
T tubules tunnel into centre
Sarcoplasmic reticulum present
Composed of myofibrils
What is the sarcoplasmic reticulum
SR is a network of fluid-filled tubules
Describe myofibrils appearance
1-2um in diameter
Extend along entire length of myofibres
Comprised of actin and myosin
What are the two main types of protein in myofibrils?
What gives muscle a striated appearance?
Light and dark bands of myofilaments
Overlapping myofibres are arranged in compartments (sarcomeres)
Describe the bands/lines in a sarcomere
Dark A band with lighter H zone (dark M line down middle)
Light I band with dark Z disc down middle
What are A and I bands made of?
A= thick myosin
I= thin actin
Outline the major changes during contraction to the bands/zones in a sarcomere (sliding filament theory)
I band shorter
A band same length
H zone narrowed (or disappeared)
Describe skeletal muscle activation and relaxation
1. AP propagates along sarcolemma into T-tubules
2. DHP (dihydropyridine) receptor in T-tubule membrane senses V and conformational change-> links to Ryanodine R (RyR) in SR and opens it
3. Ca2+ enters via SR into space around the filaments
4. Ca2+ binds to Troponin and Tropomyosin moves allowing cross bridges to attach to actin
5. Ca2+ is actively transported into SR continuously while APs continue (ATP-driven pump)
6. Ca2+ dissociates from troponin when free Ca2+ declines
7. Tropomyosin block prevents new cross bridge attachment
Active force declines due to net cross bridge detachment
List 3 examples of NMJ disorders
Botulism= botulinum toxin-> irreversible disruption in stim-induced ACh release
Myasthenia Gravis= autoimmune, antibodies against AChR
LEMS (Lambert-Eaton myasthenic syndrome)= associated with lung cancer and autoimmune, antibodies against VGCCs
List symptoms of Myasthenia Gravis
May affect ocular, bulbar, respiratory or limb muscles
Intermittent eye movement restriction/double vision/eyelid drooping (more pronounced when looking up)
Face weakness-> impaired ability to smile and speak
No other weakness and reflexes are norma
Symptoms worsen at end of day
How can Myasthenia Gravis be diagnosed?
Antibodies detected in 90% cases
Enlargement of thymus gland in younger patients
Benign tumours in older patients
How can Myasthenia Gravis be treated?
Pyridostigmine for symptomatic treatment (several times a day)
Immune suppression (steroids, other drugs to treat underlying cause)
In severe cases, antibodies in blood removed via plasma exchange
Thymectomy has therapeutic role in younger patients
Information transfer across the synapse
Requires release of neurotransmitters and their interaction with postsynaptic receptors
What are 4 features of neurotranmission
Describe a synapse
Presynaptic nerve terminal
Post synaptic region (very dense so post synaptic density)
What size is a synaptic gap?
Describe the specialised adaptations of a nerve terminal
Packed full of synaptic vesicles
Each vesicle contains approx 5000 NT molecules
Contains mitochondria (high oxidative metabolic activity)
What are the 3 stages of synaptic transmission?
Biosynthesis, packaging and release of NT
Receptor action chemical neurotransmission
Describe the function of the active zone and synaptic zone in neurotransmission
Active zone= vesicles primed and filled with NTs
Synaptic zone= vesicles docked (close to Ca2+ channels in microdomain)
List examples of neurotransmitters
GABA (y amino butyric acid)
Amines (NA, DA)
Neuropeptides (opioid peptides)
Concentrations of neurotransmitters vary from... to....
mM to nM
What does neurotransmitter binding on post-synaptic terminals lead to ?
Na+ influx -> depolarisation of post-synaptic terminal
In synaptic transmission what does NT release require?
Increase in IC Ca2+ concentration by 200 micromoles
(Calcium-dependent NT release)
How are vesicles recycled?
NTs broken down and taken up using active transport (uses ATP) back into pre-synaptic terminal
Repackaged into synaptic vesicles
Explain how neurotoxins target vesicle proteins
Zn2+ dependent endopeptides degrade the vesicle proteins and inhibit NT release
Alpha latrotoxin (black widow spider) stimulates NT release (so depletes source)
Tetanus toxin and botox target vesicle proteins
Fast excitatory and inhibitory transmission (ms) is mediated by...
Ion channel receptors
Typically pentameric complex
Slow transmission (mins) is mediated by....
G protein on cytoplasmic domain activates 2nd messenger-> amplifies effect
List ion channel-linked receptors and state whether they are excitatory or inhibitory
Nicotinic cholinergic receptors (nAChR)-> Na+ influx (excitatory)
Glutamate (GLUR) –> Na+ influx (excitatory)
GABA: Gamma amino butyric acid (GABAR)-> Cl- influx (inhibitory)
Glycine (GlyR)-> Cl- influx (inhibitory)
5HT3: 5-hydroxytryptamino receptor –> K+ efflux (inhibitory)
What are the 2 main types of GluRs
AMPA (alpha amino-3-hydroxy-5-methyl-4isoaxole propanoic acid)
What do AMPARs do?
Majority of fast excitatory synapses
Rapid onset, offset and desensitisation
Leads to Na+ influx
What do NMDARs do?
Slow component of excitatory transmission
Only activated if cell is depolarised (VG)
Leads to Na+ and Ca2+ influx
(Ca2+ acts as 2nd messenger activating other pathways)
Describe what happens at an excitatory CNS synapse in transmitter inactivation (glutamate mediated)
Glutamate synthesised in TCA (from a-ketoglutarate)
Binds with GluR on post syn membrane then removed from synaptic cleft
Removed by EAAT, excitatory AA transporter on nerve terminal and glial cells
Repackaged into synaptic vesicles
In glial cells= glutamate-> glutamine (by glutamine synthetase)
NB. Too much glutamate in synapse-> epilepsy
Describe what happens at an inhibitory CNS synapse in transmitter inactivation (GABA mediated)
Glutamate precursor to GABA-> GABA (loss of carboxyl group by GAD B6)
GABA binds with receptors
GAT (GABA transporter) takes GABA back into nerve terminal and glial cells
In glial cells= GABA-> SSA (succinate semi-aldehyde) by GABA transaminase (GABA-T)
In nerve terminal= GABA shunt (GABA-> SSA for TCA) or repackaged
Describe the pentameric organisation of the GABAR
5 binding domains
Targeted by barbituates, steroids, benzodiazepines, ethanol, zinc, convulsants
How many cases of epilepsy are unresponsive (refractory) to treatment?
A disorder of brain function characterized by the periodic and unpredictable occurrence of seizures
Transient alteration of behaviour due to the disordered, synchronous and rhythmic firing of populations of brain neurones
Thought to arise from cerebral cortex
Synchronous firing of motor neurones
Define: Partial seizures
Beginning focally at cortical site
- Complex= impaired consciousness, repeated stereotype behaviours e.g. lip-smacking (usually temporal lobe)
- Secondary generalised= begin as partial, lead to full generalised
Define: General seizures
Involve both hemispheres widely (from outset)
- Tonic clonic= most common, loss of consciousness and convulsions
- Absence= common in kids, loss of awareness
- Myoclonic= sudden stiffening of muscles
- Atonic= sudden loss of all muscle tone
What are the main neurotransmitters in epilepsy?
Decrease in GABA-mediated inhibition in hte brain
Increase in glutamate-mediated excitation in the brain
Outline pharmacological evidence for a role of NTs in epilepsy
Impaired GABA-mediated inhibition-> seizures in animals
Enhanced GABA-mediated inhibition-> seizure suppression
Some anticonvulsants (e.g. benzodiazepines, phenobarbital) potentiate GABA-mediated inhibition
Glutamate R antagonists are anticonvulsant in experimental epilepsy model
Phenobarbital blocks glutamate-mediated excitation in the brain
Outline biochemical evidence for a role of NTs in epilepsy
Cobalt-induced seizures in rodents are associated with increased glutamate release, decreased GABA conc/GAD activity/GABA uptake
Audiogenic seizures in mice associated with increased glutamate binding and decreased GABA release
List examples of antiepileptic drugs
Benzodiazepines (clonazepam, clobazam, diazepam)
How does Valproate work?
Weak effect on GABA transaminase and on Na+ channels
Used for: most types, especially absence
How does Phenobarbital work?
Enhanced GABA action
Inhibition of synaptic excitation
Used for: all except absence
How do Benzodiazepines work?
Enhanced GABA action
Used for: all types, IV to control status epilepticus
How does Vigabatrin work?
Inhibits GABA transaminase (prevents conversion to SSA)
Used for: all types (especially when patients resistant to other drugs)
How does Tiagadine work?
Reduce GABA uptake
Describe the diencephalon
Contains several nuclei with different functions
Thalamus= acts as relay station between brainstem/lower structures and cerebral cortex
Hypothalamus= coordinates homeostatic mechanisms (interface between CNS, ANS and endocrine system)
Optic chiasma= passes through optic canal to retina
Infundibulum= stalk of pituitary gland (just below hypothalamus)
What is the function of the basal ganglia?
Group of nuclei within each hemisphere
Involved in control of movement
Influence nerve signalling in brain
What is the corpus callosum?
Interconnects corresponding parts of 2 hemispheres across midline
C shaped if brain cut down mid-sagittal plane
What are the main grooves in the cortical lobes?
Deep longitudinal fissure= separates the 2 hemispheres
Central sulcus= runs medially through lateral aspect of hemisphere (frontal lobe anterior, parietal lobe posterior)
Lateral fissure= anterior to and below central sulcus (frontal lobe anterior, temporal lobe posterior)
Parietal-occipital sulcus= posterior to central sulcus (occipital lobe anterior, parietal lobe posterior)
What are the primary cortical areas?
Discrete area associated with specific functions
Primary motor cortex (involved in effector/motor functions)
Primary somatosensory (receives sensory input from body)
Primary visual (1st location to receive input from retina)
Primary auditory (1st location to receive input from inner ear)
What are the language areas?
Associated cortical areas
Dominant in L hemisphere
Broca's= forming speech
What is the ventricular system?
Structure of interlocking spaces filled with CSF within the brain
List the components of the ventricular system
Describe the lateral ventricles
2 C-shaped spaces lie on either side of the corpus callosum
Structure= anterior horn and main body
Anterior horn connects to third ventricle
Describe the 3rd ventricle
Single ventricle which bisects the diencephalon along the mid-sagittal line between the two hemispheres
The lower end forms a narrow channel= AQUEDUCT
What is the aqueduct (ventricular system)?
Narrow channel goes through the midbrain (from lower end of 3rd ventricle and then forms 4th)
Describe the 4th ventricle
Forms posterior to the brainstem anterior to the cerebellum
Forms a narrow channel= CENTRAL CANAL
What is the central canal (ventricular system)?
Narrow channel goes down from 4th ventricle to spinal cord
Describe the circulation of CSF
Secreted by choroid plexus (glands) in each ventricle
Circulates through ventricular system and subarachnoid space between meninges
Reabsorbed into the venous sinuses via arachnoid villi
Most CSF leaves through the 4th ventricle and spreads to the subarachnoid space (some goes into central canal)
How is CSF formed?
Filtration and modification of blood
So differs cellularly and in ionic contents
What are the functions of CSF?
Protection of soft tissue of brain (from gravity and trauma)
Delivery of substrates to brain tissue
What are the 3 membrane layers of the meninges?
Dura mater= tough, connective tissue inside skull (forms folds within the dural fold)
Arachnoid mater= fine membrane
Pia mater= delicate membrane surrounding the brain
How is the CSF involved in preventing increased intracranial pressure?
CSF must be returned to venous circulation to prevent increased ICP
Via pockets of the arachnoid membrane (arachnoid villi)
CSF drained into venous sinus
What occurs when CSF builds up in the brain?
What's the difference between CSF and blood?
Reduced K and Ca ion conc
Higher Mg and Cl ion conc
What is the total volume of CSF (adult)?
What is the flow rate of CSF
What is the total volume of CSF (infant)
What is the turnover of entire volume of CSF
3-4 times per day
What is the rate of production of CSF
Condition in which fluid accumulates in the brain, typically in young children, enlarging the head and sometimes causing brain damage
Can be communicating or non-communicating
What is the difference between communicating and non-communicating hydrocephalus?
Communicating hydrocephalus= all 4 ventricles affects
E.g. due to meningitis, head injury, congenital, sub-arachnoid haemorrhage
Non-communicating hydrocephalus= not all ventricles enlarged
E.g. aqueduct stenosis, ventricular tumours, paraventricular tumours
What are the symptoms of hydrocephalus?
Increases intracranial pressure
Leads to headache, nausea, blurred vision, difficulty with walking, drowsiness
How can hydrocephalus be treated?
Shunt= thin tube surgically implanted into brain, drains away excess fluid (diverts CSF)
Remove cause e.g. papilloma
Open alternate pathway e.g. ventriculostomy
Define: Epidural/extradural haemorrhage
Escape of blood from a ruptured vessel
Usually due to a damaged meningeal artery between skull and dura after head trauma
Define: Subdural haemorrhage
Usually due to a damaged vein between the dura and arachnoid membrane (venous)
Can epidural or subdural haemorrhages cause a space-occupying lesion in the confined space of the cranium and hence neurological deficits?
How can you distinguish between haemorrhages?
The first symptoms (which may be headache, drowsiness, vomiting or seizure) are likely to arise promptly after arterial bleeding in an epidural haemorrhage
Symptoms may be delayed by hours or days after venous bleeding in a subdural haemorrhage
What happens when there is bleeding between the meninges?
How can you distinguish between bacterial and viral meningitis?
High WBC count with neutrophils predominating
Protein conc increased
Glucose conc decreased
Can be 'cloudy' CSF
Predominantly lymphocytes if increased WBCs
Protein and glucose level normal
Where do these parts of the brain lie:
Frontal lobe= in anterior cranial fossa
Temporal lobe= in middle cranial fossa
Cerebrum= in posterior cranial fossa
Hypothalamus= directly above body of sphenoid bone
Medulla= passes through the foramen magnum
In which part of the brain can you find the:
Lateral ventricle= cerebral hemispheres
Third ventricle= diencephalon
Fourth ventricle= pons and medulla
Central canal= brainstem
What is electromyography (EMG)?
Recording of APs occurring in skeletal muscle fibres
Both electrodes outside the muscle fibres
Record the potential (emf) between 2 locations
List 3 examples of EC recordings?
EMG= electromyography (APs from skeletal muscle, electrodes outside muscle fibres)
ECG= electrocardiogram (APs from heart, electrodes on limbs or chest)
EEG= electroencephalogram (APs from brain, electrodes on scalp)
What is the difference between IC and EC recording?
IC recording= 1 electrode inside cell, measure emf between inside and outside cell
EC recording= both electrodes outside, measure emf between 2 sites (outside the muscle fibres)
What nerve supplies the adductor pollicis muscle (and others)?
Why are APs in muscle fibres recorded rather than APs in peripheral nerve axons?
APs in muscle fibres are of larger amplitude than those in peripheral nerve axons
Easy to record through the skin using surface electrodes
Large amplitude also means precise time recorded and any changes in amplitude detected
How can you study the adductor pollicis muscle in the thenar eminence of the hand to monitor activity of some motor axons in the ulnar nerve?
Brief pulses (approx 0.5 ms) of negative electrical current applied to pre-determined locations over the ulnar nerve using a hand-held monopolar stimulating electrode (cathode)
Anode sited at a location on the arm proximal to the cathode
Stimulating cathode over the ulnar nerve at:
S1: the medial aspect of the forearm at the wrist
S2: the ulnar groove at the elbow
(Distances between measured with tape measure)
Recording electrodes over the thenar muscle group to an amplifier and computer
6 stimuli at each location, latency of each response in ms
What does the latency time (T1 and T2) include (in ulnar nerve conduction experiment)?
Conduction delay from cathode to NMJ (delay will be greater at S2 than S2 as it's further from electrode)
Delay at NMJ
Conduction delay along muscle fibres to EMG recording electrodes
How do you calculate the conduction delay (in ulnar nerve conduction experiment)?
Subtract the response latency from SI stimulation from response latency from S2 stimulation
How do you measure conduction velocity of activated nerve axons (in ulnar nerve conduction experiment)?
Measure distance between S1 and S2
Divide by conduction delay from 2 stimulating cathodes (T2-T1)
What might slowed conduction velocity (in ulnar nerve conduction) indicate?
Increased pressure to nerve bundle
Nerve compression in forearm
What might the absence of EMG APs in response to a stimulus (in ulnar nerve conduction) indicate?
Ulnar nerve is blocked
Device is broken
What does damage to .... lead to?
Dorsal root-> loss of sensation in dermatome supplied by corresponding spinal nerve (1 root probably not detectable)
Ventral root-> weakness of muscles supplied by the corresponding spinal nerve
Spinal nerve-> combined effects of DR and VR
Sensory nerve-> loss of sensation in area of distribution of that peripheral nerve
Muscle nerve-> weakness/paralysis of muscle supplied by that peripheral nerve
What are common causes of ..... lesions?
Spinal root/spinal nerve
Spinal root and spinal nerve damage is most often due to strain injuries to the spine (prolapsed disc)
Peripheral nerves may be affected by trauma or disease (peripheral neuropathy)
Brachial plexus may be affected by trauma to the shoulder joint
Lumbosacral plexus better protected, unlikely to be injured
What is the role of the sympathetic nervous system (of ANS)?
Fight or flight response
Prepares body for responses to stressful situations
Regulates blood pressure, body temp and metabolism
What is the overall role of the parasympathetic nervous system (of ANS)?
Rest and digest
Controls functions in non-stressful conditions e.g. GI motility
Opposes the actions of the sympathetic nervous system (e.g. on HR)
Outline the parasympathetic and sympathetic effects on the....
Trachea and broncheoles
Ureters and bladder
P= pupil constriction, ciliary muscle contraction
S= pupil dilation
P= copious, watery secretion
S= thick, viscous secretion
Trachea and broncheoles
S= dilation of bronchi and bronchioles (increases O2 delivery to lungs)
S= piloerection, sweating (S cholinergic)
P= decreased rate and contractility
S= increased rate and contractility
S= glycogenolysis, gluconeogenesis
P= increased motility and tone, increased secretions, peristalsis
S= decreased motility and tone, sphincter contracting, inhibits secretory activity
S= Increased renin secretion
S= penis flaccidity, ejaculation
Ureters and bladder
P= contraction of detrusor, relaxation of trigone and internal sphincter (PELVIC NERVE)
S= relaxation of detrusor, contraction of trigone and internal sphincter (HYPOGASTRIC NERVE)
Voluntary= external sphincter (PUDENDAL NERVE)
S= constriction (skin, mucous membrane and splanchic area) and dilation (skeletal muscle)
Describe the sympathetic nerves of the ANS?
Arise in thoracic and lumbar regions of SC
Ganglia in a chain close to vertebral column (paravertebral ganglia) or close to target tissue
What do connections between ganglia (of sympathetic nerves) allow?
What acts as a modified ganglion? What is it made up of?
Only one neurone (EXCEPTION)
Made up of secretory chromaffin cells innervated by pre-ganglionic fibres
Why does the adrenal medulla contribute to a generalised effect (sympathetic nerves, ANS)?
Produces catecholamines (released directly into the bloodstream-> generalised effect)
What are the thoracolumbar (sympathetic) central origins of the ANS?
Between layers of T, L, S regions of spinal cord
Coccygeal ganglia fused together (ganglion impar)
Define: Dual innervation
Most viscera receive nerve fibres from parasympathetic and sympathetic divisions
Organs not normally innervated equally by both divisions
Define: Autonomic tone
Background rate of activity of the ANS
Balance between sympathetic and parasympathetic tone
How is the ANS involved in regulating blood pressure?
What are baroreceptors?
Arterial stretch receptors that detect high blood pressure
Found in the heart (carotid sinus and aortic arch)
What are the 2 main formulae for cardiac output?
CO = SV x HR
NB. TPR inversely proportional to radius4 so radius x 2-> TPR x 16
Define: Cardiac output
The amount of blood pumped per unit time
What effect does sympathetic stimulation of the heart have on CO?
Ionotropic effect- increased force of contraction, increased stroke volume
Chronotropic effect- increased heart rate
How is total peripheral resistance controlled?
By controlling the sympathetic tone of arteries, veins and particularly arterioles
Therefore increased activity leads to generalised vasoconstriction and increased TPR
How is mean arterial blood pressure controlled?
Increased sympathetic activity -> increased CO and increased TPR
MABP= CO x TPR so this increases MABP
What leads to vasodilation (ANS-related)?
Vasodilation mainly due to decreased sympathetic tone
How does the sympathetic nervous system increase oxygen delivery to lungs
Via noradrenaline/adrenaline from the adrenals
List examples of ANS neurotransmitters
Identify the principal loci of adrenoceptors in the ANS, their subclasses and type of GPCR
a1- smooth muscle (Gq)
a2- presynaptic nerves (Gi)
B1- heart (Gs)
B2- smooth muscle (Gs)
B3- fat tissue (Gs)
Describe the synthesis and release of noradrenaline
Tyrosine-> DOPA-> Dopamine-> Dopamine stored in vesicle-> NA-> exocytosis (due to Ca2+)
ENZYMES= tyrosine hydroxlase, DOPA decarboxylase, dopamine B hydroxylase
Describe the reuptake of noradrenaline
Uptake (back into presyn terminal)-> metabolites
Describe the synthesis and release of adrenaline
Tyrosine-> DOPA-> Dopamine-> Dopamine stored in vesicle-> NA-> Adrenaline-> adrenaline in vesicle-> exocytosis (due to Ca2+)
ENZYMES= tyrosine hydroxlase, DOPA decarboxylase, dopamine B hydroxylase, phenylethanolamine methyl transferase
In fight or flight response, what does mass sympathetic discharge in response to alarm or stress lead to?
Increased arterial blood pressure
Increased blood flow to active muscles (and decreased elsewhere)
Increased blood glucose concentration
What is the acute stress response?
Stress acts on the hypothalamus and brainstem-> catecholamine release from adrenal medulla (via sympathetic NS)
What does the acute stress response lead to?
Splanchic bed vasocontriction
Increased metabolic rate
Increased blood glucose concentration
Increase mental alertness
What feeds into the hypothalamus to prompt action by the medulla (-> parasympathetic and sympathetic activity)?
Higher brain centres
Define: Thoracolumbar outflow
The preganglionic fibres of the sympathetic system
Found in T1-T12 and L1-L3 spinal nerves
Define: Craniosacral outflow
The preganglionic fibres of the parasympathetic system
Found in cranial nerves and sacral spinal nerves
Define: Sympathetic trunk
A chain of ganglia and connecting fibres lying next to the vertebrae for the entire length of the vertebral column
Allows dispersion of the thoracolumbar sympathetic outflow to peripheral regions via all spinal nerves
A network of nerve fibres originating from different levels associated with an organ e.g. the cardiac plexus
Sympathetic anatomy: Where are the preganglionic neurones found?
Lateral column GM of SC
Sympathetic anatomy: Where do preganglionic efferent fibres arise from?
From the SC via the ventral root of the spinal nerve
Then pass through ventral ramus to white rami communicantes to ganglion (then send fibres to other ganglia via synapses)
Sympathetic anatomy: How are postganglionic fibres distributed to effector organs
Via grey rami comunicantes
What is in the sympathetic trunk?
3 ganglia in cervical region
11/12 in thoracic region
4/5 in lumbar region
4/5 in pelvis
What sympathetic plexuses are found in the cervical region?
Plexus around pharynx
What sympathetic plexuses are found in the thoracic region?
Plexus around thoracic aorta
To do with abdomen plexus= Splanchic nerves:
Greater- thoracic aorta supply, pierces diaphragm, enters abdomen plexus around great blood vessels supplying gut
Lesser- pierces diaphragm, enters abdomen plexus around aorta
Least- pierces diaphragm, enters abdomen plexus around gut
What sympathetic plexuses are found in the lumbar region?
4 lumbar ganglia
Lumbar splanchic nerves take part in all plexuses in abdominal and pelvis regions
Parasympathetic anatomy: Where is the sacral outflow?
Anterior rami of S2-4
Visceral branches pass directly to pelvic viscera
Minute ganglia in wall of viscera giving rise to postganglionic fibres
Parasympathetic anatomy: What are the pelvic splanchic nerves?
Motor fibres to rectum
Motor fibres to bladder wall
Inhibitory fibres to bladder sphincter
Erection of penis/clitoris via vasodilator fibres
Fibres also pass superiorly to supply large part of the gut with visceromotor innervation
Which cranial nerves contain parasympathetic preganglion and what are their associated origin nuclei?
Oculomotor (3)- Edinger Westphal nucleus
Facial (7)- Superior salivatory nucleus
Glossopharyngeal (9)- Inferior salivatory nucleus
Vagus (10)- Dorsal nucleus of the vagus and nucleus ambiguus
What is the associated parasympathetic ganglion of:
Ciliary ganglion (postganglionic fibres to sphincter pupillae and ciliary muscle)
Submandibular ganglion (postganglionic fibres to submandibular and sublingual salivary glands)
Pterygopalatine ganglion (postganglionic fibre to paranasal sinuses and lacrimal glands)
Otic ganglion (postganglionic fibres to parotid gland)
Enters neck and thorax via carotid sheath
Branches to lungs, heart, oesophagus, stomach, intestines
Describe the enteric system
In walls of alimentary tract
Sensory- monitoring mechanical, chemical and hormonal activity of gut
Motor- gut motility, secretion, vessel tone
Can be overriden by sympathetic and parasympathetic systems
How do baroreceptors respond predominantly to stretch of blood vessels (due to BP)?
Modified nerve endings of baroreceptors in carotid sinus and aortic arch
When stimulated, what do baroreceptors signal to?
Which then passes signal to sympathetic ganglia of the ANS
What happens when arterial blood pressure is increased?
Increased stretch of baroreceptors
-> Increased afferent nerve activity to brain
-> Increased inhibition of sympathetic nervous system
-> Blood pressure reduced
How does reducing sympathetic activity (increasing inhibition) lead to reduced blood pressure?
Inhibition of SNS:
Decreased vasomotor tone-> decreased TPR
Decreased HR and force of contraction-> decreased CO
Decreased circulating catecholamines from adrenal medulla
What happens when arterial blood pressure is increased?
Reduced stretch of baroreceptors
-> Reduced afferent nerve activity to brain
-> Reduced inhibition of sympathetic nervous system
-> Blood pressure increased
How does increasing sympathetic activity (reducing inhibition) lead to increased blood pressure?
Increased activation of SNS:
Increased vasomotor tone-> increased TPR
Increased HR and force of contraction-> increased CO
Increased circulating catecholamines from adrenal medulla
Also increases vagal tone
What blood pressure changes occur when standing upright?
Increased pooling of blood in lower limbs
Reduced venous return-> reduced contractility
Reduced blood pressure
Then baroreceptors respond to reduced stimulation to increase blood pressure
What is postural hypotension caused by?
Impaired autonomic (mostly sympathetic) nerve response
Little change in CO
No increase in TPR
Acute reduced sympathetic response
What does postural hypotension lead to?
Arterial blood pressure not maintained on standing
Decreased cerebral blood flow-> faint
(Blood flow restored when supine, consciousness restored)
Describe the pupillary light reflex
Pupil constricts in response to light
Photosensitive photoganglion cells
Edinger Westphal nuclei
What is the role of the iris in contraction of the pupil?
Increased parasympathetic activity-> elongation of iris-> contraction of pupil
Pilocarpine= ACh analogue that stimulates parasympathetic activity (miosis)
What is the role of the iris in dilation of the pupil?
Increased sympathetic activity-> iris contracts-> dilates pupil
Atropine stimulates the sympathetic nervous system (mydriasis)
What is the role of photoganglion cells in the consensual reflex?
Photosensitive photoganglion cells detect light
Sensory input carried by optic nerve (2) to the pretectal nucleus in the brain (bypassing visual cortex)
Pretectal nucleus activity sends impulses to Edinger Westphal nuclei
What is the role of the Edinger Westphal nuclei in the consensual reflex?
EW nuclei act as the parasympathetic activity origin
Parasympathetic activity via occulomotor nerve (3) to ciliary ganglion
Postganglionic fibre then carries the activity to the sphincter pupillus (constricts the pupil)