Neuroscience and Mental Health Flashcards

1
Q

The nervous system is divided (2)

A

Central Nervous System

Peripheral Nervous System

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2
Q

CNS includes

A

Brain

Spinal Cord

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3
Q

PNS includes

A

Nerves

Ganglia (clusters of neuronal cell bodies)

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4
Q

PNS functionally divided into (2)

A

Somatic (motor and sensory divisions)

Autonomic (motor and sensory divisions)

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5
Q

What is the Somatic PNS?

A

Controls motor and sensory function for the body wall e.g. skin (sensory neurone) and skeletal muscles (motor neurone)

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6
Q

What is the Autonomic NS?

A

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

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7
Q

The type of nerves in the sympathetic division of the ANS are…

A

Spinal nerves

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8
Q

The type of nerves in the parasympathetic division of the ANS are…

A

Spinal nerves

Cranial nerves

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9
Q

The type of nerves in Somatic NS are…

A

Spinal nerves

Cranial nerves

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10
Q

Brain is composed of (3)

A

Cerebral cortex (cerebrum)
Cerebellum
Brainstem

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11
Q

Describe the input/output to cerebral cortex

A

2 hemispheres

Each receives sensory info and controls movement of opposite side of the body

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12
Q

What is the function of the cerebellum?

A

Controls motor coordination (movement) and involved in learning motor skills

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13
Q

Describe the brainstem

A

Most primitive part
Densely packed fibres
Regulates vital functions (e.g. consciousness, breathing)
Damage here usually serious (can be fatal)

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14
Q

What are the dorsal and ventral roots of the spinal cord?

A

Dorsal and ventral roots that emerge from the SC

Are part of the PNS

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15
Q

Describe the overall process of neurotransmission (not ions just overall action of NTs)

A

An AP reaches a neuronal chemical synapse

NTs released by presynaptic terminal bind to post-synaptic receptors

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16
Q

What are the differences between the regenerative capacities of injured axons in the CNS and PNS?

A

CNS
Unable to regenerate over long enough distances to be useful
Inhibitory molecules

PNS
Axons in PNS can regenerate after injury
No inhibitory molecules

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17
Q

How is regeneration/recovery compromised in the NS?

A

Recovery compromised by non-specific target re-innervation and aberrant axon sprouting
Absence of guidance cues to stimulate axon growth during development

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18
Q

Define: Afferent axons

A

Axons entering CNS
Propagate APs towards brain and spinal cord from PNS
E.g. sensory neurons (somatic and ANS)

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19
Q

Define: Efferent axons

A

Axons leaving CNS
Propagate APs from brain and spinal cord to PNS
E.g. motor neurons (somatic and ANS)

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20
Q

Define: Interneurons

A

CNS neurones that synapse with other CNS neurones within brain or spinal cord

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21
Q

What do somatic sensory neurons convey?

A

Convey sensory info from body to SC and then there to sensory cortex
Stimulate reflex activity

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22
Q

Where is sensation perceived?

A

Sensory cortex

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23
Q

Are the sensory and motor cortex anatomically distinct?

A

Yes

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24
Q

What does white matter comprise of?

A

Ascending and descending axon tracts to/from the brain

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25
Q

What are needed for a reflex response?

A

Somatic sensory inputs-> (interneurons)-> motor outputs from SC
Neurones must be intact

NOT communication with sensorimotor cortex

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26
Q

What is required for conscious registering of a sensory stimulus?

A

Sensory inputs activate sensory neurones in grey matter of SC (ascending tracts-> sensory cortex of the brain)

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27
Q

What happens to neurones from the motor cortex?

A

Axons extend downward to synapse with spinal motor neurones and transmit APs (descending tracts)
Important for voluntary movement

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28
Q

CASE
Lost voluntary movement and sensation in L arm
Muscles show reflex activity
CAUSE?

A
Likely to be injury to R hemisphere 
Close to sensorimotor cortex 
Not peripheral nerve (reflex intact)
Not SC (only 1 arm)
Probably stroke
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29
Q

CASE
Lost voluntary movement and sensation in L arm
Muscles don’t show reflex activity
CAUSE?

A

Likely to involve periphery (lose reflex)
Not SC (only 1 arm)
Probably due to fall

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30
Q

CASE
Lost voluntary movement in L arm and leg
Muscles show reflex activity
CAUSE?

A

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?

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31
Q

What is neurology?

A

Study of brain, SC, peripheral nerves and muscle

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32
Q

What components are there in a standard neurological exam?

A
Gait and station
Cranial nerves
Motor
Sensation
Mental state
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33
Q

MMSE (mini mental state exam) categories

A

Orientation
Registration

TRIALS
Attention and calculation
Recall
Language

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34
Q

MMSE: Orientation

A

Year, season, date, day, month

Country, city, part of city, house no., street name

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35
Q

MMSE: Registration

A

3 objects said by Dr
Repeated until patient remembers all 3
Count trials and record

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36
Q

MMSE: Trials- attention and calculation

A

Serial 7s- 1 point for each correct
Stop after 5

OR

Spell ‘world’ backwards

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37
Q

MMSE: Trials- Recall

A

Ask for 3 objects in registration phase

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38
Q

MMSE: Trials- Language

A

Name certain items, repeat certain phrases, follow 3 stage command etc.

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39
Q

5 stages of diagnosing neurological problems

A

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)
Syndromic formulation

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40
Q

What does an EEG do?

A

Electroencephalography

Measures electrical potentials at scalp generated by underlying neurones
Useful for diagnosing epilepsy and coma

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41
Q

What are EMG and NCS used for?

A

Electromyography and nerve conduction studies

Examines integrity of muscle, peripheral nerve and lower motor neurones

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42
Q

How are CTs used in neurological diagnosis?

A

Computerised tomography

Uses X-ray source, high conc. of ionising radiation
Shows hard tissues well
Relatively fast and inexpensive

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43
Q

How are MRIs used in neurological diagnosis?

A

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
Non invasive

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44
Q

What do lumbar punctures study and where can it be obtained from?

A

Cerebrospinal fluid

Between L3 and L4 AND L4 and L5

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45
Q

What can be used for neurological diagnosis?

A

Neurophysiology= EEG, EMG, NCS
Imaging= CT, MRI
Lumbar puncture

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46
Q

What causes a stroke?

A

80% blockage of blood vessel (infarct- which may be caused by carotid arteries in neck)
20% bleeding (haemorrhage often related to high BP)

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47
Q

Where can strokes affect?

A

Any part of the brain (including brainstem)
Tends to cause problems contralateral to brain lesion
Symptoms relate to which artery in brain is affected

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48
Q

What are stroke risk factors?

A

Smokers
Family history
Diabetes
Excess alcohol

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49
Q

Why can strokes cause aphasia?

A

Left side of brain responsible for language

Strokes here can lead to aphasia

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50
Q

Where do strokes most commonly affect and what symptoms does it cause?

A

Middle cerebral artery

Results in weakness and loss of sensation on the other side

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51
Q

What are the symptoms of posterior cerebral artery strokes?

A

Affect occipital lobe

Result in visual loss on contralateral side

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52
Q

What are the symptoms of anterior cerebral artery strokes?

A

Often cause contralateral leg weakness

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53
Q

What are the symptoms of strokes affecting the brainstem?

A

Problems with balance
Eye movements
Speech and swallowing
Breathing

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54
Q

Stroke treatment: Acute

A

Intravenous thrombolysis- dissolve clot

Intra-arterial thrombectomy- remove clot

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55
Q

Stroke treatment: Complications

A

Neurosurgery for haemorrhage or dangerously high pressure

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56
Q

Stroke treatment: Prevent further stroke

A

Thin blood with aspirin
Treat diabetes and high cholesterol
Treat dangerously narrow carotid arteries

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57
Q

What neurotransmitter is associated with Parkinson’s disease?

A

Dopamine

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58
Q

What are PD patients treated with? And why not Dopamine?

A

Levodopa
Dopamine doesn’t cross BBB but levodopa crosses BBB and then converted into dopamine

Also treated with deep brain stimulation (DBS)

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59
Q

What are the causes of Spastic Parapesis?

A

Trauma
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

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60
Q

What is Multiple Myeloma?

A

Tumour of plasma cells

Treated with radiotherapy and chemotherapy

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61
Q

What causes Acute Polyneuropathy?

A

Infections e.g. Diptheria
Autoimmune e.g. Guillain Barre
Drugs e.g. chemo
Exposure to toxins e.g. organophosphate insecticides

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62
Q

What is GBS/AIDP?

A

Common cause of acute neuromuscular weakness
Clinical diagnosis
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

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63
Q

What is the treatment for GBS/AIDP?

A

Immunotherapy= plasma exchange or IV immunoglobulin
Supportive e.g. ventilation
Cardiac monitoring
Anticoagulation to prevent leg clots (and subsequent pulmonary emboli)

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64
Q

What are the symptoms of Parkinsonism?

A
Impassive faces
Soft, monotonous speech
Slow shuffling gait
Stooped
Loss of arm swing
Pill-rolling tremor
Increased tone and cogwheeling
Bradykinesia
Micrographia (small handwriting)
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65
Q

What is a neurone?

A

Basic structural and functional unit of the NS
Info processing
Responsible for generating/conducting electrical signals
Supported by neuroglia
Highly organise metabolically active secretory cell

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66
Q

What is the ratio neuroglia:neurones

A

9:1

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67
Q

Describe neuronal structure

A

Cellular structure of all neurones is similar (diversity achieved by differences in number and shape of their processes)

Large nucleus
Prominent nucleolus
Abundant RER
Well developed Golgi 
Abundant mitochondria
Highly organised cytoskeleton
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68
Q

What is a dendrite (input)?

A

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)

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69
Q

What is an axon (output)?

A
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
Cable properties 
Organised into (molecular) domains
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70
Q

What are the domains in an axon?

A

Paranode
Node
Juxta-paranode

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71
Q

What is an axon terminal?

A

Axons often branch extensively close to target (terminal arbor)
From synaptic terminals with target

Either bouton (synapse) or varicosities (in smooth muscle cells)

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72
Q

What are synapses?

A

Between cells
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

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73
Q

Neurones can be excitatory, inhibitory or modulatory. Which types are which?

A
Axo-dendritic= often excitatory
Axo-somatic= often inhibitory
Axo-axonic= often modulatory
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74
Q

Neurofilaments play a critical role in what (to do with neuronal cytoskeleton)?

A

Axon caliber

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75
Q

Name the main intracellular transport types (functional polarization)?

A

Fast axonal transport
Anterograde transport
Retrograde transport

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76
Q

What is fast axonal transport?

A

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

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77
Q

What is anterograde transport?

A

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

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78
Q

What is retrograde transport?

A

Fast= return of organelles
Transport of substances from EC space
Uses different molecular motors
E.g. Trophic growth factors, neurotrophic viruses

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79
Q

What is the size range of cell bodies?

A

5 micrometers to 135 micrometers

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80
Q

Describe DRG sensory neurones

A

Pseudounipolar
2 fused axonal processes
No dendrites (receive no synapses)
Have a soma

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81
Q

Describe bipolar neurones?

A

Two axonal processes with central soma

E.g. in cerebral cortex, retina

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82
Q

Describe Golgi Type I Multipolar cells

A

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

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83
Q

Describe Golgi Type II Multipolar cells

A

Highly branched dendritic trees
Short axons terminating quite close to the cell body of origin

E.g. stellate cells of cerebral cortex and cerebellum

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84
Q

Describe pyramidal cells of the cerebral cortex

A

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)

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85
Q

Describe stellate cells of the cerebral cortex and cerebellum

A

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

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86
Q

What are the functional subtypes of neurones?

A

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)

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87
Q

What are the functional organisational groups of neurones?

A
Nucleus
Laminae 
Ganglion
Fibre tracts
Nerves
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88
Q

Functional organisation: describe nucleus

A

Group of unencapsulated neuronal cell bodies within the CNS
Usually consist of functionally similar cells
E.g. Raphe nuclei

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89
Q

Functional organisation: describe laminae

A

Layers of neurones of similar type and function

E.g. cerebral cortex grey matter

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90
Q

Functional organisation: describe ganglion

A

Group of encapsulated neuronal cell bodies within the PNS

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91
Q

Functional organisation: describe fibre tracts

A

Groups or bundles of axons in the CNS
Mixture of myelinated and unmyelinated
E.g. corpus callosum, internal capsule

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92
Q

Functional organisation: describe nerves

A

Discrete bundles of axons
Bring info to CNS and to effector organs
Often mixed sensory and motor neurones
Usually part of PNS

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93
Q

Describe the role of neuroglia

A

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

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94
Q

Describe astroglia

A

Multi-processed star-like shape
Most numerous cell type
Numerous intermediate filament bundles in cytoplasm of fibrous astroglia
Gap junctions suggest astroglia-astroglia signalling

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95
Q

Describe the functions of astroglia

A

Scaffold for neuronal migration and axon growth
Development
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
Barrier functions

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96
Q

What are oligodendroglia?

A
Myelin forming cells of the CNS
(Interfasicular oligodendroglia and perineuronal oligodendroglia)
Small spherical nuclei
Few thin processes
Prominent ER and Golgi
Metabolically highly active
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97
Q

What are the functions of oligodendroglia?

A

Produce/maintain myelin sheath

Each cell produces multiple sheaths (1-40)

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98
Q

What is myelin?

A

Lipid rich insulating membrane up to 50 lamellae
Dark and light bands at EM level
Loss of oligodendroglia and myelin has disastrous consequences

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99
Q

What diseases are caused by faulty myelin?

A

Multiple sclerosis

Adrneoleucodystrophy

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100
Q

What are microglia?

A

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
Synaptic stripping
Phagocytic when diseased (in inflammation)

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101
Q

What are peripheral glia?

A
Schwann cells
Myelin producing cells of the PNS
Each Schwann cell produces only 1 myelin sheath
Surround unmyelinated axons
Promote axon regeneration
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102
Q

Define Multiple Sclerosis

A

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

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103
Q

Symptoms of MS

A
Visual e.g. double vision
Motor (evenutal paralysiss)
Sensory
Cognitive and psychiatric
Bowel, bladder
Sexual
Speech issues
Vomiting 
Off-balance= dizzy
Onset= hours to days
Recovery= days to months
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104
Q

How do you diagnose MS?

A

Clinical history
MRI (hyperintense white spot signals)
CSF analysis (increased immunoglobulin production)
-> Oligoclonal bands by electrophoresis (has to be matched with blood)

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105
Q

What are the clinical subtypes of MS?

A
Relapsing-remitting (complete or incomplete recovery relapses)
Secondary progressive (relapses with increased worsening of disability and recovery)
Primary progressive (increased disability with no recovery)
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106
Q

Epidemiology of MS

A

20-40 years old

More frequently in females

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107
Q

What therapy is used for MS?

A

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)

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108
Q

Define: flux (relevant to diffusion)

A

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

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109
Q

What are the properties of ions?

A

Charged molecules
Opposite charges attract
Like charges repel

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110
Q

Units of electrical properties

A

Voltage (pd)= volts (ions produce a charge gdt)
Current= amps (movement of ions due to pd)
Resistance= ohms (barrier that prevents movement of ions)

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111
Q

How do you measure membrane potential?

A

Reference electrode placed outside cell (0V level)
Another electrode inside cell
Measures voltage difference (-ve compared with outside)
All cells have a membrane potential

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112
Q

Describe ion channels

A

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

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113
Q

Define electrochemical equilibrium

A

For an ion reached when its concentration gradient is balanced by the electrical gradient across the membrane

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114
Q

What is the Nernst equation and what does it show?

A

Equilibrium potential of X ion (mV)
SEE FORMULA

R= gas constant
T= temp (Kelvin)
Z= valency
F= Faraday's number (coulombs of charge per mol of ion)
Ln= natural log
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115
Q

Recall typical concentrations for ions (IC and EC)

A
.....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)
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116
Q

What is the equilibrium potential for K+?

A

-90mV

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117
Q

What is the equilibrium potential for Na+?

A

+72mV

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118
Q

What is the typical Em?

A

-70mV

Membrane more permeable to K

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119
Q

Why is the membrane closer to K+ equilibrium potential?

A

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

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120
Q

What is the Goldman Hodgkin Katz equation?

A

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

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121
Q

What do different values for P (permeability/channel open probability) mean?

A
0= 100% closed
1= 100% open
0.5= open 50% of time
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122
Q

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

A
  • 14mV
  • 90mV
  • 66mV
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123
Q

Which membrane potential tends towards 0 (away from RMP)?

A

Depolarising

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124
Q

Which membrane potential tends above zero towards Na equilibrium potential?

A

Overshoot

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125
Q

Which membrane potential tends away from RMP but in same direction as repolarisation (leads to membrane potential closer to K equilibrium potential)?

A

Hyperpolarising

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126
Q

Which membrane potential tends towards the RMP?

A

Repolarising

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127
Q

What are graded potentials?

A

Change in membrane potential in response to stimulation and occur at synapses and sensory receptors
Contribute/initiate/prevent APs

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128
Q

Defining characteristics of graded potentials?

A

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

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129
Q

What is decremental spread? (Regarding graded potentials)

A

Magnitude of membrane potential change decreases with time and with distance from stimulus site

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130
Q

What effect does temperature change have of equilibrium potential of an ion?

A

Increased temp-> increased permeability-> membrane leaky

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131
Q

What are regenerative capacities?

A

CNS axons don’t spontaneously regenerate after injury in adult mammals
PNS axons readily regenerate, allowing recovery of function after peripheral nerve damage

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132
Q

What are action potentials?

A

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

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133
Q

What cells are electrically excitable?

A

Muscle fibres

Neurones

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134
Q

Define: Threshold

A

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

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135
Q

Define: Refractory state

A

Period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation

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136
Q

Define: All or nothing

A

Once triggered, a full sized AP occurs

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137
Q

Define: Saltatory conduction

A

Propagation of APs along myelinated axons from one node of Ranvier to next node, increasing conduction velocity of APs

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138
Q

Define: Voltage-gated ion channels

A

Transmembrane ion channels activated by changes in electrical membrane potential near the channel e.g. for Na and K

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139
Q

Define: Channel inactivation

A

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

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140
Q

Define: Positive feedback

A

Enhancing or amplification of an effect by its own influence on the process which gives rise to it
Occurs in Na channels in AP

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141
Q

Sequence of events in typical AP

A
RMP
Depolarizing stimulus
Upstroke
Repolarisation
Hyperpolarisation 
RMP
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142
Q

What causes the upstroke in an AP?

A

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

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143
Q

What causes repolarization in an AP?

A

VGSCs inactivated
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

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144
Q

What is the absolute refractory period?

A

Inactivation gate is closed

New AP can’t be triggered even with very strong stimulus

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145
Q

What causes hyperpolarization in an AP?

A

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

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146
Q

What is the relative refractory period?

A

Na inactivation gate open

Stronger than normal stimulus required to trigger an AP

147
Q

Are changes in membrane potential during APs due to ion pumps?

A

No

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)

148
Q

How long do APs last?

A

1msec

149
Q

Describe the regenerative relationship between Na permeability and membrane potential

A

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

150
Q

How does passive propagation/transmission/conduction of AP along the axon occur?

A

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)

151
Q

What is the velocity of APs?

A

Travels quickly
Velocity ranges
Large diameter, myelinated axons= 120m/s
Small diameter, non-myelinated axons=1m/s

152
Q

What affects conduction velocity?

A

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)

153
Q

Name 2 pathological conditions affecting conduction velocity

A

Multiple sclerosis

Diptheria

154
Q

What does the brain develop from (and into how many divisions)?

A

From neural tube

3 main divisions= forebrain, midbrain, hindbrain

155
Q

What divides the 2 hemispheres?

A

Mid-saggital line (with diencephalon sitting between the 2 heminspheres)

156
Q

What cover the hemispheres?

A

Cerebral cortex with gyri and sulci

157
Q

What is the groove between 2 hemispheres?

A

Deep longitudinal fissure

158
Q

What is the forebrain comprised of?

A

Cerebral hemispheres

Diencephalon

159
Q

What is the hindbrain comprised of?

A

Pons
Medulla
Cerebellum

160
Q

What part of the spinal cord has a sensory function and which has a motor function?

A

Dorsal horns= sensory, grey matter

Ventral horns= motor, grey matter

161
Q

What is the brainstem?

A

Midbrain
Pons
Medulla

162
Q

Describe the dorsal and ventral horns of the spinal cord (cross-section)

A

Grey matter ‘butterfly’ with DH (sensory) and VH (motor)
Dorsal root (has DRG)
Ventral root
Roots-> spinal nerve

163
Q

What spinal segments are higher than their corresponding vertebrae?

A

Lumbar and sacral

164
Q

Describe the sensory input pathway in spinal cord

A

Dorsal root ganglia and dorsal roots

Dorsal horn of GM in SC

165
Q

Describe the motor output pathway in spinal cord

A

Ventral horn of GM in SC

Ventral roots

166
Q

What protects the spinal cord?

A

Segmented structure= vertical column

167
Q

What does the vertebral column consist of?

A

Vertebrae surrounding SC
Separated by cartilage rings (shock absorbers)
Intervertebral foramina (gaps between the arches laterally allows spinal nerves to emerge horizontally)

168
Q

How many spinal nerves are associated with vertebrae?

A

31

169
Q

What are the types of vertebrae?

A

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)

NB. coccyx+coccygeal

170
Q

What is longer, the spinal cord or the vertebral column?

A

Vertebral column

This means spinal and vertebral levels are not level (note for lumbar puncture- to protect SC, below L2, ideally L3-4)

171
Q

What does the PNS consist of?

A
Peripheral nerves (axons)
Ganglia (soma)
172
Q

What are peripheral nerves subdivided into?

A

Spinal

Cranial

173
Q

What are ganglia in the brain called?

A

Basal ganglia

174
Q

Describe sensory neurones (autonomic and somatic) in the PNS

A

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)

175
Q

Describe autonomic neurones (general) in the PNS

A

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

176
Q

Describe autonomic sensory neurones in the PNS

A

Impulses travel from body periphery via DRG into DH of GM in SC

177
Q

Describe autonomic motor neurones in the PNS

A

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

178
Q

Describe somatic (general) neurones in the PNS

A

Soma in CNS

Impulses pass along ventral root through spinal nerve to appropriate skeletal muscle and trigger contraction

179
Q

Describe somatic sensory neurones in the PNS

A

Impulses travel from periphery of body via DRG into the DH of GM within the SC

180
Q

Describe somatic motor neurones in the PNS

A

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

181
Q

Describe the development of spinal cord and how it relates to GM and WM

A

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

182
Q

Describe glia (microscopic organisation)

A

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)

183
Q

Describe bundles of axons in PNS

A

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)

184
Q

What are the layers of connective tissue around the myelin sheath of each myelinated nerve fibre?

A

Endoneurium
Perneurium
Epineurium

185
Q

What is the endoneurium?

A

Individual axons and their associated Schwann cells are surrounded by delicate loose connective tissue

186
Q

What is the perineurium?

A

Groups of axons (fascicle) surrounded by dense connective tissue

187
Q

What is the epineurium?

A

Whole nerve surrounded by loose connective tissue

188
Q

What factors affect conduction velocity of peripheral axons?

A

Myelination

Unmyelinated= usually small (1um)
Clothed in cytoplasm of Schwann cells (neurolemma) which can accomodate several axons per Schwann cell
Slow conduction speed= 1ms

Myelinated= 1.5-20um
Clothed in succession of Schwann cells (each wrapping tightly around the axon in up to 100 layers)

189
Q

Describe how the myelin sheath is present in the PNS

A

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

190
Q

Are there Na channels in Schwann cells?

A

No
Depolarisation can’t occur
Cells therefore act as electrical insulators

191
Q

Why are myelinated axons more energy efficient?

A

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)

192
Q

Give an example of the fastest and slowest axon group

A
Fastest= muscle spindle primary afferent (120m/sec)
Slowest= C-pain fibre (1m/sec)
193
Q

Define: Dermatome

A

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)

194
Q

Define: Myotome

A

Group of muscles that a single spinal nerve root innervates

195
Q

Define: Ramus

A

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

196
Q

What do the rami communicants (WM and GM) provide?

A

Interconnections between some spinal nerves and ganglia of the sympathetic NS

197
Q

Define: Plexus (and brachial plexus/lumbosacral plexus)

A

Branching network of intersecting nerves

Brachial plexus= ventral rami of spinal nerves C5-T1
Lumbosacral plexus= ventral rami of L2-S2

198
Q

Describe how spinal nerves are arranged in the main trunk and how they innervate limbs

A

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)

199
Q

What are peripheral neuropathies?

A

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

200
Q

How can you detect whether a neuropathy is present (if demyelinating or axonal)

A

Conduction velocity

201
Q

How can you study pathogenesis of a neuropathic disease?

A

Nerve biopsy

E.g. sural nerve to study pathogenesis of the disease

202
Q

Define: Neuromuscular junction

A

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

203
Q

What are the typical contact ratio of synapses in the muscle and CNS

A

1: 1 for muscle
1000: 1 in the CNS

204
Q

Outline the 7 step process to initiate muscle contraction (at the NMJ)

A
  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
205
Q

What causes miniature end-plate potentials? (mEPPs)

A

Individual vesicles releasing ACh at a very low rate

206
Q

What are myofibres?

A
Multi-nucleated single muscle cell
Covered by sarcolemma (surface membrane)
T tubules tunnel into centre
Sarcoplasmic reticulum present
Composed of myofibrils
207
Q

What is the sarcoplasmic reticulum

A

SR is a network of fluid-filled tubules

208
Q

Describe myofibrils appearance

A

1-2um in diameter
Extend along entire length of myofibres
Comprised of actin and myosin

209
Q

What are the two main types of protein in myofibrils?

A

Actin

Myosin

210
Q

What gives muscle a striated appearance?

A

Light and dark bands of myofilaments

Overlapping myofibres are arranged in compartments (sarcomeres)

211
Q

Describe the bands/lines in a sarcomere

A

Dark A band with lighter H zone (dark M line down middle)

Light I band with dark Z disc down middle

Z-Z= sarcomere

212
Q

What are A and I bands made of?

A
A= thick myosin
I= thin actin
213
Q

Outline the major changes during contraction to the bands/zones in a sarcomere (sliding filament theory)

A

I band shorter
A band same length
H zone narrowed (or disappeared)

214
Q

Describe skeletal muscle activation and relaxation

A
  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

215
Q

List 3 examples of NMJ disorders

A

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

216
Q

List symptoms of Myasthenia Gravis

A

“Fatiguable weakness”
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

217
Q

How can Myasthenia Gravis be diagnosed?

A

Antibodies detected in 90% cases
EMG exam
Enlargement of thymus gland in younger patients
Benign tumours in older patients

218
Q

How can Myasthenia Gravis be treated?

A
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
219
Q

Define: Neurotransmission

A

Information transfer across the synapse

Requires release of neurotransmitters and their interaction with postsynaptic receptors

220
Q

What are 4 features of neurotranmission

A

Rapid timescale
Diversity
Adaptability
Plasticity

221
Q

Describe a synapse

A

Asymmetric

Presynaptic nerve terminal
Synaptic gap
Post synaptic region (very dense so post synaptic density)

222
Q

What size is a synaptic gap?

A

20-100nm

223
Q

Describe the specialised adaptations of a nerve terminal

A

Packed full of synaptic vesicles
Each vesicle contains approx 5000 NT molecules
Contains mitochondria (high oxidative metabolic activity)

224
Q

What are the 3 stages of synaptic transmission?

A

Biosynthesis, packaging and release of NT
Receptor action chemical neurotransmission
Transmitter inactivation

225
Q

Describe the function of the active zone and synaptic zone in neurotransmission

A

Active zone= vesicles primed and filled with NTs

Synaptic zone= vesicles docked (close to Ca2+ channels in microdomain)

226
Q

List examples of neurotransmitters

A
Glutamate
GABA (y amino butyric acid)
Glycine
Amines (NA, DA)
Neuropeptides (opioid peptides)
227
Q

Concentrations of neurotransmitters vary from… to….

A

mM to nM

228
Q

What does neurotransmitter binding on post-synaptic terminals lead to ?

A

Na+ influx -> depolarisation of post-synaptic terminal

229
Q

In synaptic transmission what does NT release require?

A

Increase in IC Ca2+ concentration by 200 micromoles

Calcium-dependent NT release

230
Q

How are vesicles recycled?

A

NTs broken down and taken up using active transport (uses ATP) back into pre-synaptic terminal
Repackaged into synaptic vesicles

231
Q

Explain how neurotoxins target vesicle proteins

A
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
232
Q

Fast excitatory and inhibitory transmission (ms) is mediated by…

A

Ion channel receptors

Typically pentameric complex

233
Q

Slow transmission (mins) is mediated by….

A

GPCRs

G protein on cytoplasmic domain activates 2nd messenger-> amplifies effect

234
Q

List ion channel-linked receptors and state whether they are excitatory or inhibitory

A

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)

235
Q

What are the 2 main types of GluRs

A

AMPA (alpha amino-3-hydroxy-5-methyl-4isoaxole propanoic acid)
NMDA (N-methyl-D-aspartate)

236
Q

What do AMPARs do?

A

Majority of fast excitatory synapses
Rapid onset, offset and desensitisation
Leads to Na+ influx

237
Q

What do NMDARs do?

A

Slow component of excitatory transmission
Coincidence detectors
Only activated if cell is depolarised (VG)
Leads to Na+ and Ca2+ influx
(Ca2+ acts as 2nd messenger activating other pathways)

238
Q

Describe what happens at an excitatory CNS synapse in transmitter inactivation (glutamate mediated)

A

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

239
Q

Describe what happens at an inhibitory CNS synapse in transmitter inactivation (GABA mediated)

A

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

240
Q

Describe the pentameric organisation of the GABAR

A

5 binding domains

Targeted by barbituates, steroids, benzodiazepines, ethanol, zinc, convulsants

241
Q

How many cases of epilepsy are unresponsive (refractory) to treatment?

A

30%

242
Q

Define: Epilepsy

A

A disorder of brain function characterized by the periodic and unpredictable occurrence of seizures

243
Q

Define: Seizure

A

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

244
Q

Define: Partial seizures

A

Beginning focally at cortical site

Can be:

  • Simple
  • Complex= impaired consciousness, repeated stereotype behaviours e.g. lip-smacking (usually temporal lobe)
  • Secondary generalised= begin as partial, lead to full generalised
245
Q

Define: General seizures

A

Involve both hemispheres widely (from outset)

Can be:

  • 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
246
Q

What are the main neurotransmitters in epilepsy?

A

Decrease in GABA-mediated inhibition in hte brain

Increase in glutamate-mediated excitation in the brain

247
Q

Outline pharmacological evidence for a role of NTs in epilepsy

A

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

248
Q

Outline biochemical evidence for a role of NTs in epilepsy

A

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

249
Q

List examples of antiepileptic drugs

A

Valproate
Phenobarbital
Benzodiazepines (clonazepam, clobazam, diazepam)
Vigabatrin

250
Q

How does Valproate work?

A

Weak effect on GABA transaminase and on Na+ channels

Used for: most types, especially absence

251
Q

How does Phenobarbital work?

A

Enhanced GABA action
Inhibition of synaptic excitation

Used for: all except absence

252
Q

How do Benzodiazepines work?

A

Enhanced GABA action

Used for: all types, IV to control status epilepticus

253
Q

How does Vigabatrin work?

A

Inhibits GABA transaminase (prevents conversion to SSA)

Used for: all types (especially when patients resistant to other drugs)

254
Q

How does Tiagadine work?

A

Reduce GABA uptake

255
Q

Describe the diencephalon

A

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)

256
Q

What is the function of the basal ganglia?

A

Group of nuclei within each hemisphere
Involved in control of movement
Influence nerve signalling in brain

257
Q

What is the corpus callosum?

A

Interconnects corresponding parts of 2 hemispheres across midline
C shaped if brain cut down mid-sagittal plane

258
Q

What are the main grooves in the cortical lobes?

A

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)

259
Q

What are the primary cortical areas?

A

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)
260
Q

What are the language areas?

A

Associated cortical areas
Dominant in L hemisphere
Wernicke’s= comprehension
Broca’s= forming speech

261
Q

What is the ventricular system?

A

Structure of interlocking spaces filled with CSF within the brain

262
Q

List the components of the ventricular system

A

Lateral ventricle
Third ventricle
Fourth ventricle

263
Q

Describe the lateral ventricles

A

2 C-shaped spaces lie on either side of the corpus callosum
Structure= anterior horn and main body
Anterior horn connects to third ventricle

264
Q

Describe the 3rd ventricle

A

Single ventricle which bisects the diencephalon along the mid-sagittal line between the two hemispheres
The lower end forms a narrow channel= AQUEDUCT

265
Q

What is the aqueduct (ventricular system)?

A

Narrow channel goes through the midbrain (from lower end of 3rd ventricle and then forms 4th)

266
Q

Describe the 4th ventricle

A

Forms posterior to the brainstem anterior to the cerebellum

Forms a narrow channel= CENTRAL CANAL

267
Q

What is the central canal (ventricular system)?

A

Narrow channel goes down from 4th ventricle to spinal cord

268
Q

Describe the circulation of CSF

A

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)

269
Q

How is CSF formed?

A

Filtration and modification of blood

So differs cellularly and in ionic contents

270
Q

What are the functions of CSF?

A

Protection of soft tissue of brain (from gravity and trauma)
Metabolic functions
Waste removal
Delivery of substrates to brain tissue

271
Q

What are the 3 membrane layers of the meninges?

A

Dura mater= tough, connective tissue inside skull (forms folds within the dural fold)
Arachnoid mater= fine membrane
Pia mater= delicate membrane surrounding the brain

272
Q

How is the CSF involved in preventing increased intracranial pressure?

A

CSF must be returned to venous circulation to prevent increased ICP
Via pockets of the arachnoid membrane (arachnoid villi)
CSF drained into venous sinus

273
Q

What occurs when CSF builds up in the brain?

A

Hydrocephalus

274
Q

What’s the difference between CSF and blood?

A
CSF has...
Fewer cells
Less protein
Reduced K and Ca ion conc
Higher Mg and Cl ion conc
275
Q

What is the total volume of CSF (adult)?

A

150ml

276
Q

What is the flow rate of CSF

A

500ml/day

277
Q

What is the total volume of CSF (infant)

A

50ml

278
Q

What is the turnover of entire volume of CSF

A

3-4 times per day

279
Q

What is the rate of production of CSF

A

0.35ml/min (500ml/day)

280
Q

Define: Hydrocephalus

A

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

281
Q

What is the difference between communicating and non-communicating hydrocephalus?

A

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

282
Q

What are the symptoms of hydrocephalus?

A

Increases intracranial pressure

Leads to headache, nausea, blurred vision, difficulty with walking, drowsiness

283
Q

How can hydrocephalus be treated?

A

Shunt= thin tube surgically implanted into brain, drains away excess fluid (diverts CSF)
Remove cause e.g. papilloma
Open alternate pathway e.g. ventriculostomy

284
Q

Define: Epidural/extradural haemorrhage

A

Escape of blood from a ruptured vessel

Usually due to a damaged meningeal artery between skull and dura after head trauma

285
Q

Define: Subdural haemorrhage

A

Usually due to a damaged vein between the dura and arachnoid membrane (venous)

286
Q

Can epidural or subdural haemorrhages cause a space-occupying lesion in the confined space of the cranium and hence neurological deficits?

A

Both

287
Q

How can you distinguish between haemorrhages?

A

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

288
Q

What happens when there is bleeding between the meninges?

A

Stroke

289
Q

How can you distinguish between bacterial and viral meningitis?

A

CSF analysis

BACTERIAL
High WBC count with neutrophils predominating
Protein conc increased
Glucose conc decreased
Can be 'cloudy' CSF

VIRAL
Predominantly lymphocytes if increased WBCs
Protein and glucose level normal

290
Q
Where do these parts of the brain lie:
Frontal lobe
Temporal lobe
Cerebrum
Hypothalamus
Medulla
A

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

291
Q
In which part of the brain can you find the:
Lateral ventricle
Third ventricle
Aqueduct
Fourth ventricle
Central canal
A
Lateral ventricle= cerebral hemispheres
Third ventricle= diencephalon
Aqueduct= midbrain
Fourth ventricle= pons and medulla
Central canal= brainstem
292
Q

What is electromyography (EMG)?

A

Recording of APs occurring in skeletal muscle fibres
Both electrodes outside the muscle fibres
Record the potential (emf) between 2 locations

293
Q

List 3 examples of EC recordings?

A
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)
294
Q

What is the difference between IC and EC recording?

A

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)

295
Q

What nerve supplies the adductor pollicis muscle (and others)?

A

Ulnar nerve

296
Q

Why are APs in muscle fibres recorded rather than APs in peripheral nerve axons?

A

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

297
Q

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?

A

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

298
Q

What does the latency time (T1 and T2) include (in ulnar nerve conduction experiment)?

A

Activation time
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

299
Q

How do you calculate the conduction delay (in ulnar nerve conduction experiment)?

A

Subtract the response latency from SI stimulation from response latency from S2 stimulation

300
Q

How do you measure conduction velocity of activated nerve axons (in ulnar nerve conduction experiment)?

A

Measure distance between S1 and S2
Divide by conduction delay from 2 stimulating cathodes (T2-T1)

Speed= m/s

301
Q

What might slowed conduction velocity (in ulnar nerve conduction) indicate?

A

Demyelination
Hypothermia
Increased pressure to nerve bundle
Nerve compression in forearm

302
Q

What might the absence of EMG APs in response to a stimulus (in ulnar nerve conduction) indicate?

A

Ulnar nerve is blocked

Device is broken

303
Q

What does damage to …. lead to?

Dorsal root
Ventral root
Spinal nerve
Sensory nerve
Muscle nerve
A

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

304
Q
What are common causes of ..... lesions? 
Spinal root/spinal nerve 
Peripheral nerve
Brachial plexus
Lumbosacral plexus
A

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

305
Q

What is the role of the sympathetic nervous system (of ANS)?

A

Fight or flight response
Prepares body for responses to stressful situations
Regulates blood pressure, body temp and metabolism

306
Q

What is the overall role of the parasympathetic nervous system (of ANS)?

A

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)

307
Q

Outline the parasympathetic and sympathetic effects on the….

Eye
Salivary glands
Trachea and broncheoles
Skin
Heart
Liver
GI tract
Adipose 
Kidney
Ureters and bladder
Blood vessels
A

Eye
P= pupil constriction, ciliary muscle contraction
S= pupil dilation

Salivary glands
P= copious, watery secretion
S= thick, viscous secretion

Trachea and broncheoles
P= constriction
S= dilation of bronchi and bronchioles (increases O2 delivery to lungs)

Skin
S= piloerection, sweating (S cholinergic)

Heart
P= decreased rate and contractility
S= increased rate and contractility

Liver
S= glycogenolysis, gluconeogenesis

GI tract
P= increased motility and tone, increased secretions, peristalsis
S= decreased motility and tone, sphincter contracting, inhibits secretory activity

Adipose
S= lipolysis

Kidney
S= Increased renin secretion

Penis
P= erection
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)

Blood vessels
S= constriction (skin, mucous membrane and splanchic area) and dilation (skeletal muscle)

308
Q

Describe the sympathetic nerves of the ANS?

A

Arise in thoracic and lumbar regions of SC
Pre-ganglionic= short
Post-ganglionic= long
Ganglia in a chain close to vertebral column (paravertebral ganglia) or close to target tissue

309
Q

What do connections between ganglia (of sympathetic nerves) allow?

A

Mass activation

310
Q

What acts as a modified ganglion? What is it made up of?

A

Adrenal medulla
Only one neurone (EXCEPTION)
Made up of secretory chromaffin cells innervated by pre-ganglionic fibres

311
Q

Why does the adrenal medulla contribute to a generalised effect (sympathetic nerves, ANS)?

A

Produces catecholamines (released directly into the bloodstream-> generalised effect)

312
Q

What are the thoracolumbar (sympathetic) central origins of the ANS?

A

Between layers of T, L, S regions of spinal cord

Coccygeal ganglia fused together (ganglion impar)

313
Q

Define: Dual innervation

A

Most viscera receive nerve fibres from parasympathetic and sympathetic divisions
Organs not normally innervated equally by both divisions

314
Q

Define: Autonomic tone

A

Background rate of activity of the ANS

Balance between sympathetic and parasympathetic tone

315
Q

How is the ANS involved in regulating blood pressure?

A

Baroreceptors

316
Q

What are baroreceptors?

A

Arterial stretch receptors that detect high blood pressure

Found in the heart (carotid sinus and aortic arch)

317
Q

What are the 2 main formulae for cardiac output?

A
CO = SV x HR
CO= MABP/TPR 

NB. TPR inversely proportional to radius4 so radius x 2-> TPR x 16

318
Q

Define: Cardiac output

A

The amount of blood pumped per unit time

319
Q

What effect does sympathetic stimulation of the heart have on CO?

A

Ionotropic effect- increased force of contraction, increased stroke volume
Chronotropic effect- increased heart rate

320
Q

How is total peripheral resistance controlled?

A

By controlling the sympathetic tone of arteries, veins and particularly arterioles
Therefore increased activity leads to generalised vasoconstriction and increased TPR

321
Q

How is mean arterial blood pressure controlled?

A

Increased sympathetic activity -> increased CO and increased TPR

MABP= CO x TPR so this increases MABP

322
Q

What leads to vasodilation (ANS-related)?

A

Vasodilation mainly due to decreased sympathetic tone

323
Q

How does the sympathetic nervous system increase oxygen delivery to lungs

A

Via noradrenaline/adrenaline from the adrenals

324
Q

List examples of ANS neurotransmitters

A

Acetylcholine
Noradrenaline
Adrenaline

325
Q

Identify the principal loci of adrenoceptors in the ANS, their subclasses and type of GPCR

A
a1- smooth muscle (Gq)
a2- presynaptic nerves (Gi)
B1- heart (Gs)
B2- smooth muscle (Gs)
B3- fat tissue (Gs)
326
Q

Describe the synthesis and release of noradrenaline

A

Tyrosine-> DOPA-> Dopamine-> Dopamine stored in vesicle-> NA-> exocytosis (due to Ca2+)

ENZYMES= tyrosine hydroxlase, DOPA decarboxylase, dopamine B hydroxylase

327
Q

Describe the reuptake of noradrenaline

A

Degradation (COMT)
Uptake (back into presyn terminal)-> metabolites

ENZYME= MAO

328
Q

Describe the synthesis and release of adrenaline

A

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

329
Q

In fight or flight response, what does mass sympathetic discharge in response to alarm or stress lead to?

A
Increased arterial blood pressure
Increased blood flow to active muscles (and decreased elsewhere)
Increased blood glucose concentration
Increased respiration
Increased awareness
330
Q

What is the acute stress response?

A

Stress acts on the hypothalamus and brainstem-> catecholamine release from adrenal medulla (via sympathetic NS)

331
Q

What does the acute stress response lead to?

A
Tachycardia
Splanchic bed vasocontriction
Increased metabolic rate
Sweating
Pupil dilation
Increased blood glucose concentration 
Increase mental alertness
332
Q

What feeds into the hypothalamus to prompt action by the medulla (-> parasympathetic and sympathetic activity)?

A

Higher brain centres

Homeostatic changes

333
Q

Define: Thoracolumbar outflow

A

The preganglionic fibres of the sympathetic system

Found in T1-T12 and L1-L3 spinal nerves

334
Q

Define: Craniosacral outflow

A

The preganglionic fibres of the parasympathetic system

Found in cranial nerves and sacral spinal nerves

335
Q

Define: Sympathetic trunk

A

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

336
Q

Define: Plexus

A

A network of nerve fibres originating from different levels associated with an organ e.g. the cardiac plexus

337
Q

Sympathetic anatomy: Where are the preganglionic neurones found?

A

Lateral column GM of SC

T1-L3

338
Q

Sympathetic anatomy: Where do preganglionic efferent fibres arise from?

A

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)

339
Q

Sympathetic anatomy: How are postganglionic fibres distributed to effector organs

A

Via grey rami comunicantes

340
Q

What is in the sympathetic trunk?

A

3 ganglia in cervical region
11/12 in thoracic region
4/5 in lumbar region
4/5 in pelvis

341
Q

What sympathetic plexuses are found in the cervical region?

A

Plexus around pharynx
Cardiac plexus
Thyroid plexus
Pulmonary plexus

342
Q

What sympathetic plexuses are found in the thoracic region?

A

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

343
Q

What sympathetic plexuses are found in the lumbar region?

A

4 lumbar ganglia
Lumbar splanchic nerves take part in all plexuses in abdominal and pelvis regions

Trick Q

344
Q

Parasympathetic anatomy: Where is the sacral outflow?

A

Anterior rami of S2-4
Visceral branches pass directly to pelvic viscera
Minute ganglia in wall of viscera giving rise to postganglionic fibres

345
Q

Parasympathetic anatomy: What are the pelvic splanchic nerves?

A

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

346
Q

Which cranial nerves contain parasympathetic preganglion and what are their associated origin nuclei?

A

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

347
Q
What is the associated parasympathetic ganglion of:
CN3
CN7
CN9
CN10
A
CN3
Ciliary ganglion (postganglionic fibres to sphincter pupillae and ciliary muscle)
CN7
Submandibular ganglion (postganglionic fibres to submandibular and sublingual salivary glands)
Pterygopalatine ganglion (postganglionic fibre to paranasal sinuses and lacrimal glands)
CN9
Otic ganglion (postganglionic fibres to parotid gland)

CN10
Enters neck and thorax via carotid sheath
Branches to lungs, heart, oesophagus, stomach, intestines

348
Q

Describe the enteric system

A

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

349
Q

How do baroreceptors respond predominantly to stretch of blood vessels (due to BP)?

A

Modified nerve endings of baroreceptors in carotid sinus and aortic arch

350
Q

When stimulated, what do baroreceptors signal to?

A

Medulla

Which then passes signal to sympathetic ganglia of the ANS

351
Q

What happens when arterial blood pressure is increased?

A

Increased stretch of baroreceptors

  • > Increased afferent nerve activity to brain
  • > Increased inhibition of sympathetic nervous system
  • > Blood pressure reduced
352
Q

How does reducing sympathetic activity (increasing inhibition) lead to reduced blood pressure?

A

Inhibition of SNS:
Decreased vasomotor tone-> decreased TPR
Decreased HR and force of contraction-> decreased CO
Decreased circulating catecholamines from adrenal medulla

353
Q

What happens when arterial blood pressure is increased?

A

Reduced stretch of baroreceptors

  • > Reduced afferent nerve activity to brain
  • > Reduced inhibition of sympathetic nervous system
  • > Blood pressure increased
354
Q

How does increasing sympathetic activity (reducing inhibition) lead to increased blood pressure?

A

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

355
Q

What blood pressure changes occur when standing upright?

A

Increased pooling of blood in lower limbs
Reduced venous return-> reduced contractility
Reduced CO
Reduced blood pressure

Then baroreceptors respond to reduced stimulation to increase blood pressure

356
Q

What is postural hypotension caused by?

A

Impaired autonomic (mostly sympathetic) nerve response

This causes:
Little change in CO
No increase in TPR
Acute reduced sympathetic response
Postural hypotension
357
Q

What does postural hypotension lead to?

A

Arterial blood pressure not maintained on standing
Decreased cerebral blood flow-> faint

(Blood flow restored when supine, consciousness restored)

358
Q

Describe the pupillary light reflex

A

Largely parasympathetic
Pupil constricts in response to light
Consensual reflex

Involves:
Iris
Photosensitive photoganglion cells
Edinger Westphal nuclei

359
Q

What is the role of the iris in contraction of the pupil?

A

Increased parasympathetic activity-> elongation of iris-> contraction of pupil

Pilocarpine= ACh analogue that stimulates parasympathetic activity (miosis)

360
Q

What is the role of the iris in dilation of the pupil?

A

Increased sympathetic activity-> iris contracts-> dilates pupil

Atropine stimulates the sympathetic nervous system (mydriasis)

361
Q

What is the role of photoganglion cells in the consensual reflex?

A

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

362
Q

What is the role of the Edinger Westphal nuclei in the consensual reflex?

A

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)

363
Q

What does it mean if the only 1 eye constricts when light is shone on 1 eye?

A

Problem with motor function after the EW nuclei