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
What are needed for a reflex response?
Somatic sensory inputs-> (interneurons)-> motor outputs from SC Neurones must be intact NOT communication with sensorimotor cortex
26
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)
27
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
28
CASE Lost voluntary movement and sensation in L arm Muscles show reflex activity CAUSE?
``` Likely to be injury to R hemisphere Close to sensorimotor cortex Not peripheral nerve (reflex intact) Not SC (only 1 arm) Probably stroke ```
29
CASE Lost voluntary movement and sensation in L arm Muscles don't show reflex activity CAUSE?
Likely to involve periphery (lose reflex) Not SC (only 1 arm) Probably due to fall
30
CASE Lost voluntary movement in L arm and leg Muscles show reflex activity CAUSE?
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?
31
What is neurology?
Study of brain, SC, peripheral nerves and muscle
32
What components are there in a standard neurological exam?
``` Gait and station Cranial nerves Motor Sensation Mental state ```
33
MMSE (mini mental state exam) categories
Orientation Registration TRIALS Attention and calculation Recall Language
34
MMSE: Orientation
Year, season, date, day, month | Country, city, part of city, house no., street name
35
MMSE: Registration
3 objects said by Dr Repeated until patient remembers all 3 Count trials and record
36
MMSE: Trials- attention and calculation
Serial 7s- 1 point for each correct Stop after 5 OR Spell 'world' backwards
37
MMSE: Trials- Recall
Ask for 3 objects in registration phase
38
MMSE: Trials- Language
Name certain items, repeat certain phrases, follow 3 stage command etc.
39
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) Syndromic formulation
40
What does an EEG do?
Electroencephalography Measures electrical potentials at scalp generated by underlying neurones Useful for diagnosing epilepsy and coma
41
What are EMG and NCS used for?
Electromyography and nerve conduction studies Examines integrity of muscle, peripheral nerve and lower motor neurones
42
How are CTs used in neurological diagnosis?
Computerised tomography Uses X-ray source, high conc. of ionising radiation Shows hard tissues well Relatively fast and inexpensive
43
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 Non invasive
44
What do lumbar punctures study and where can it be obtained from?
Cerebrospinal fluid | Between L3 and L4 AND L4 and L5
45
What can be used for neurological diagnosis?
Neurophysiology= EEG, EMG, NCS Imaging= CT, MRI Lumbar puncture
46
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)
47
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
48
What are stroke risk factors?
Smokers Family history Diabetes Excess alcohol
49
Why can strokes cause aphasia?
Left side of brain responsible for language | Strokes here can lead to aphasia
50
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
51
What are the symptoms of posterior cerebral artery strokes?
Affect occipital lobe | Result in visual loss on contralateral side
52
What are the symptoms of anterior cerebral artery strokes?
Often cause contralateral leg weakness
53
What are the symptoms of strokes affecting the brainstem?
Problems with balance Eye movements Speech and swallowing Breathing
54
Stroke treatment: Acute
Intravenous thrombolysis- dissolve clot | Intra-arterial thrombectomy- remove clot
55
Stroke treatment: Complications
Neurosurgery for haemorrhage or dangerously high pressure
56
Stroke treatment: Prevent further stroke
Thin blood with aspirin Treat diabetes and high cholesterol Treat dangerously narrow carotid arteries
57
What neurotransmitter is associated with Parkinson's disease?
Dopamine
58
What are PD patients treated with? And why not Dopamine?
Levodopa Dopamine doesn't cross BBB but levodopa crosses BBB and then converted into dopamine Also treated with deep brain stimulation (DBS)
59
What are the causes of Spastic Parapesis?
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
60
What is Multiple Myeloma?
Tumour of plasma cells | Treated with radiotherapy and chemotherapy
61
What causes Acute Polyneuropathy?
Infections e.g. Diptheria Autoimmune e.g. Guillain Barre Drugs e.g. chemo Exposure to toxins e.g. organophosphate insecticides
62
What is GBS/AIDP?
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
63
What is the treatment for GBS/AIDP?
Immunotherapy= plasma exchange or IV immunoglobulin Supportive e.g. ventilation Cardiac monitoring Anticoagulation to prevent leg clots (and subsequent pulmonary emboli)
64
What are the symptoms of Parkinsonism?
``` Impassive faces Soft, monotonous speech Slow shuffling gait Stooped Loss of arm swing Pill-rolling tremor Increased tone and cogwheeling Bradykinesia Micrographia (small handwriting) ```
65
What is a neurone?
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
66
What is the ratio neuroglia:neurones
9:1
67
Describe neuronal structure
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 ```
68
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)
69
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 Cable properties Organised into (molecular) domains ```
70
What are the domains in an axon?
Paranode Node Juxta-paranode
71
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)
72
What are synapses?
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
73
Neurones can be excitatory, inhibitory or modulatory. Which types are which?
``` Axo-dendritic= often excitatory Axo-somatic= often inhibitory Axo-axonic= often modulatory ```
74
Neurofilaments play a critical role in what (to do with neuronal cytoskeleton)?
Axon caliber
75
Name the main intracellular transport types (functional polarization)?
Fast axonal transport Anterograde transport Retrograde transport
76
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
77
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
78
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
79
What is the size range of cell bodies?
5 micrometers to 135 micrometers
80
Describe DRG sensory neurones
Pseudounipolar 2 fused axonal processes No dendrites (receive no synapses) Have a soma
81
Describe bipolar neurones?
Two axonal processes with central soma | E.g. in cerebral cortex, retina
82
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
83
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
84
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)
85
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
86
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)
87
What are the functional organisational groups of neurones?
``` Nucleus Laminae Ganglion Fibre tracts Nerves ```
88
Functional organisation: describe nucleus
Group of unencapsulated neuronal cell bodies within the CNS Usually consist of functionally similar cells E.g. Raphe nuclei
89
Functional organisation: describe laminae
Layers of neurones of similar type and function | E.g. cerebral cortex grey matter
90
Functional organisation: describe ganglion
Group of encapsulated neuronal cell bodies within the PNS
91
Functional organisation: describe fibre tracts
Groups or bundles of axons in the CNS Mixture of myelinated and unmyelinated E.g. corpus callosum, internal capsule
92
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
93
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
94
Describe astroglia
Multi-processed star-like shape Most numerous cell type Numerous intermediate filament bundles in cytoplasm of fibrous astroglia Gap junctions suggest astroglia-astroglia signalling
95
Describe the functions of astroglia
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
96
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 ```
97
What are the functions of oligodendroglia?
Produce/maintain myelin sheath | Each cell produces multiple sheaths (1-40)
98
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
99
What diseases are caused by faulty myelin?
Multiple sclerosis | Adrneoleucodystrophy
100
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 Synaptic stripping Phagocytic when diseased (in inflammation)
101
What are peripheral glia?
``` Schwann cells Myelin producing cells of the PNS Each Schwann cell produces only 1 myelin sheath Surround unmyelinated axons Promote axon regeneration ```
102
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
103
Symptoms of MS
``` 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 ```
104
How do you diagnose MS?
Clinical history MRI (hyperintense white spot signals) CSF analysis (increased immunoglobulin production) -> Oligoclonal bands by electrophoresis (has to be matched with blood)
105
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) ```
106
Epidemiology of MS
20-40 years old | More frequently in females
107
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)
108
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
109
What are the properties of ions?
Charged molecules Opposite charges attract Like charges repel
110
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)
111
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
112
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
113
Define electrochemical equilibrium
For an ion reached when its concentration gradient is balanced by the electrical gradient across the membrane
114
What is the Nernst equation and what does it show?
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 ```
115
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) ```
116
What is the equilibrium potential for K+?
-90mV
117
What is the equilibrium potential for Na+?
+72mV
118
What is the typical Em?
-70mV | Membrane more permeable to K
119
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
120
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
121
What do different values for P (permeability/channel open probability) mean?
``` 0= 100% closed 1= 100% open 0.5= open 50% of time ```
122
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
- 14mV - 90mV - 66mV
123
Which membrane potential tends towards 0 (away from RMP)?
Depolarising
124
Which membrane potential tends above zero towards Na equilibrium potential?
Overshoot
125
Which membrane potential tends away from RMP but in same direction as repolarisation (leads to membrane potential closer to K equilibrium potential)?
Hyperpolarising
126
Which membrane potential tends towards the RMP?
Repolarising
127
What are graded potentials?
Change in membrane potential in response to stimulation and occur at synapses and sensory receptors Contribute/initiate/prevent APs
128
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
129
What is decremental spread? (Regarding graded potentials)
Magnitude of membrane potential change decreases with time and with distance from stimulus site
130
What effect does temperature change have of equilibrium potential of an ion?
Increased temp-> increased permeability-> membrane leaky
131
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
132
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
133
What cells are electrically excitable?
Muscle fibres | Neurones
134
Define: Threshold
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
135
Define: Refractory state
Period immediately following stimulation during which a nerve or muscle is unresponsive to further stimulation
136
Define: All or nothing
Once triggered, a full sized AP occurs
137
Define: Saltatory conduction
Propagation of APs along myelinated axons from one node of Ranvier to next node, increasing conduction velocity of APs
138
Define: Voltage-gated ion channels
Transmembrane ion channels activated by changes in electrical membrane potential near the channel e.g. for Na and K
139
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
140
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
141
Sequence of events in typical AP
``` RMP Depolarizing stimulus Upstroke Repolarisation Hyperpolarisation RMP ```
142
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
143
What causes repolarization in an AP?
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
144
What is the absolute refractory period?
Inactivation gate is closed | New AP can't be triggered even with very strong stimulus
145
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
146
What is the relative refractory period?
Na inactivation gate open | Stronger than normal stimulus required to trigger an AP
147
Are changes in membrane potential during APs due to ion pumps?
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
How long do APs last?
1msec
149
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
150
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)
151
What is the velocity of APs?
Travels quickly Velocity ranges Large diameter, myelinated axons= 120m/s Small diameter, non-myelinated axons=1m/s
152
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)
153
Name 2 pathological conditions affecting conduction velocity
Multiple sclerosis | Diptheria
154
What does the brain develop from (and into how many divisions)?
From neural tube | 3 main divisions= forebrain, midbrain, hindbrain
155
What divides the 2 hemispheres?
Mid-saggital line (with diencephalon sitting between the 2 heminspheres)
156
What cover the hemispheres?
Cerebral cortex with gyri and sulci
157
What is the groove between 2 hemispheres?
Deep longitudinal fissure
158
What is the forebrain comprised of?
Cerebral hemispheres | Diencephalon
159
What is the hindbrain comprised of?
Pons Medulla Cerebellum
160
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
161
What is the brainstem?
Midbrain Pons Medulla
162
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) Ventral root Roots-> spinal nerve
163
What spinal segments are higher than their corresponding vertebrae?
Lumbar and sacral
164
Describe the sensory input pathway in spinal cord
Dorsal root ganglia and dorsal roots | Dorsal horn of GM in SC
165
Describe the motor output pathway in spinal cord
Ventral horn of GM in SC | Ventral roots
166
What protects the spinal cord?
Segmented structure= vertical column
167
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)
168
How many spinal nerves are associated with vertebrae?
31
169
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) NB. coccyx+coccygeal
170
What is longer, the spinal cord or the vertebral column?
Vertebral column | This means spinal and vertebral levels are not level (note for lumbar puncture- to protect SC, below L2, ideally L3-4)
171
What does the PNS consist of?
``` Peripheral nerves (axons) Ganglia (soma) ```
172
What are peripheral nerves subdivided into?
Spinal | Cranial
173
What are ganglia in the brain called?
Basal ganglia
174
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)
175
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
176
Describe autonomic sensory neurones in the PNS
Impulses travel from body periphery via DRG into DH of GM in SC
177
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
178
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
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Describe somatic sensory neurones in the PNS
Impulses travel from periphery of body via DRG into the DH of GM within the SC
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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
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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
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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)
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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)
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What are the layers of connective tissue around the myelin sheath of each myelinated nerve fibre?
Endoneurium Perneurium Epineurium
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What is the endoneurium?
Individual axons and their associated Schwann cells are surrounded by delicate loose connective tissue
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What is the perineurium?
Groups of axons (fascicle) surrounded by dense connective tissue
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What is the epineurium?
Whole nerve surrounded by loose connective tissue
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What factors affect conduction velocity of peripheral axons?
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
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
190
Are there Na channels in Schwann cells?
No Depolarisation can't occur Cells therefore act as electrical insulators
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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)
192
Give an example of the fastest and slowest axon group
``` Fastest= muscle spindle primary afferent (120m/sec) Slowest= C-pain fibre (1m/sec) ```
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Define: Dermatome
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)
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Define: Myotome
Group of muscles that a single spinal nerve root innervates
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Define: Ramus
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
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What do the rami communicants (WM and GM) provide?
Interconnections between some spinal nerves and ganglia of the sympathetic NS
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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
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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)
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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
200
How can you detect whether a neuropathy is present (if demyelinating or axonal)
Conduction velocity
201
How can you study pathogenesis of a neuropathic disease?
Nerve biopsy | E.g. sural nerve to study pathogenesis of the disease
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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
203
What are the typical contact ratio of synapses in the muscle and CNS
1: 1 for muscle 1000: 1 in the CNS
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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
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What causes miniature end-plate potentials? (mEPPs)
Individual vesicles releasing ACh at a very low rate
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What are myofibres?
``` Multi-nucleated single muscle cell Covered by sarcolemma (surface membrane) T tubules tunnel into centre Sarcoplasmic reticulum present Composed of myofibrils ```
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What is the sarcoplasmic reticulum
SR is a network of fluid-filled tubules
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Describe myofibrils appearance
1-2um in diameter Extend along entire length of myofibres Comprised of actin and myosin
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What are the two main types of protein in myofibrils?
Actin | Myosin
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What gives muscle a striated appearance?
Light and dark bands of myofilaments | Overlapping myofibres are arranged in compartments (sarcomeres)
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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 Z-Z= sarcomere
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What are A and I bands made of?
``` A= thick myosin I= thin actin ```
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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)
214
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
215
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
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List symptoms of Myasthenia Gravis
"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
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How can Myasthenia Gravis be diagnosed?
Antibodies detected in 90% cases EMG exam Enlargement of thymus gland in younger patients Benign tumours in older patients
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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 ```
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Define: Neurotransmission
Information transfer across the synapse | Requires release of neurotransmitters and their interaction with postsynaptic receptors
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What are 4 features of neurotranmission
Rapid timescale Diversity Adaptability Plasticity
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Describe a synapse
Asymmetric Presynaptic nerve terminal Synaptic gap Post synaptic region (very dense so post synaptic density)
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What size is a synaptic gap?
20-100nm
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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)
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What are the 3 stages of synaptic transmission?
Biosynthesis, packaging and release of NT Receptor action chemical neurotransmission Transmitter inactivation
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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)
226
List examples of neurotransmitters
``` Glutamate GABA (y amino butyric acid) Glycine Amines (NA, DA) Neuropeptides (opioid peptides) ```
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Concentrations of neurotransmitters vary from... to....
mM to nM
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What does neurotransmitter binding on post-synaptic terminals lead to ?
Na+ influx -> depolarisation of post-synaptic terminal
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In synaptic transmission what does NT release require?
Increase in IC Ca2+ concentration by 200 micromoles | Calcium-dependent NT release
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How are vesicles recycled?
NTs broken down and taken up using active transport (uses ATP) back into pre-synaptic terminal Repackaged into synaptic vesicles
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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 ```
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Fast excitatory and inhibitory transmission (ms) is mediated by...
Ion channel receptors | Typically pentameric complex
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Slow transmission (mins) is mediated by....
GPCRs | G protein on cytoplasmic domain activates 2nd messenger-> amplifies effect
234
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)
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What are the 2 main types of GluRs
AMPA (alpha amino-3-hydroxy-5-methyl-4isoaxole propanoic acid) NMDA (N-methyl-D-aspartate)
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What do AMPARs do?
Majority of fast excitatory synapses Rapid onset, offset and desensitisation Leads to Na+ influx
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What do NMDARs do?
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)
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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
239
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
240
Describe the pentameric organisation of the GABAR
5 binding domains | Targeted by barbituates, steroids, benzodiazepines, ethanol, zinc, convulsants
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How many cases of epilepsy are unresponsive (refractory) to treatment?
30%
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Define: Epilepsy
A disorder of brain function characterized by the periodic and unpredictable occurrence of seizures
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Define: Seizure
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
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Define: Partial seizures
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
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Define: General seizures
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
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What are the main neurotransmitters in epilepsy?
Decrease in GABA-mediated inhibition in hte brain | Increase in glutamate-mediated excitation in the brain
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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
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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
249
List examples of antiepileptic drugs
Valproate Phenobarbital Benzodiazepines (clonazepam, clobazam, diazepam) Vigabatrin
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How does Valproate work?
Weak effect on GABA transaminase and on Na+ channels Used for: most types, especially absence
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How does Phenobarbital work?
Enhanced GABA action Inhibition of synaptic excitation Used for: all except absence
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How do Benzodiazepines work?
Enhanced GABA action Used for: all types, IV to control status epilepticus
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How does Vigabatrin work?
Inhibits GABA transaminase (prevents conversion to SSA) Used for: all types (especially when patients resistant to other drugs)
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How does Tiagadine work?
Reduce GABA uptake
255
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)
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What is the function of the basal ganglia?
Group of nuclei within each hemisphere Involved in control of movement Influence nerve signalling in brain
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What is the corpus callosum?
Interconnects corresponding parts of 2 hemispheres across midline C shaped if brain cut down mid-sagittal plane
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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)
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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) ```
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What are the language areas?
Associated cortical areas Dominant in L hemisphere Wernicke's= comprehension Broca's= forming speech
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What is the ventricular system?
Structure of interlocking spaces filled with CSF within the brain
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List the components of the ventricular system
Lateral ventricle Third ventricle Fourth ventricle
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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
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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
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What is the aqueduct (ventricular system)?
Narrow channel goes through the midbrain (from lower end of 3rd ventricle and then forms 4th)
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Describe the 4th ventricle
Forms posterior to the brainstem anterior to the cerebellum | Forms a narrow channel= CENTRAL CANAL
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What is the central canal (ventricular system)?
Narrow channel goes down from 4th ventricle to spinal cord
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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)
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How is CSF formed?
Filtration and modification of blood | So differs cellularly and in ionic contents
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What are the functions of CSF?
Protection of soft tissue of brain (from gravity and trauma) Metabolic functions Waste removal Delivery of substrates to brain tissue
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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
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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
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What occurs when CSF builds up in the brain?
Hydrocephalus
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What's the difference between CSF and blood?
``` CSF has... Fewer cells Less protein Reduced K and Ca ion conc Higher Mg and Cl ion conc ```
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What is the total volume of CSF (adult)?
150ml
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What is the flow rate of CSF
500ml/day
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What is the total volume of CSF (infant)
50ml
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What is the turnover of entire volume of CSF
3-4 times per day
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What is the rate of production of CSF
0.35ml/min (500ml/day)
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Define: Hydrocephalus
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
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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
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What are the symptoms of hydrocephalus?
Increases intracranial pressure | Leads to headache, nausea, blurred vision, difficulty with walking, drowsiness
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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
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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
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Define: Subdural haemorrhage
Usually due to a damaged vein between the dura and arachnoid membrane (venous)
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Can epidural or subdural haemorrhages cause a space-occupying lesion in the confined space of the cranium and hence neurological deficits?
Both
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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
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What happens when there is bleeding between the meninges?
Stroke
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How can you distinguish between bacterial and viral meningitis?
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
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``` Where do these parts of the brain lie: Frontal lobe Temporal lobe Cerebrum Hypothalamus Medulla ```
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
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``` In which part of the brain can you find the: Lateral ventricle Third ventricle Aqueduct Fourth ventricle Central canal ```
``` Lateral ventricle= cerebral hemispheres Third ventricle= diencephalon Aqueduct= midbrain Fourth ventricle= pons and medulla Central canal= brainstem ```
292
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
293
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) ```
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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)
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What nerve supplies the adductor pollicis muscle (and others)?
Ulnar nerve
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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
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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
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What does the latency time (T1 and T2) include (in ulnar nerve conduction experiment)?
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
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
300
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) Speed= m/s
301
What might slowed conduction velocity (in ulnar nerve conduction) indicate?
Demyelination Hypothermia Increased pressure to nerve bundle Nerve compression in forearm
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What might the absence of EMG APs in response to a stimulus (in ulnar nerve conduction) indicate?
Ulnar nerve is blocked | Device is broken
303
What does damage to .... lead to? ``` Dorsal root Ventral root Spinal nerve Sensory nerve Muscle nerve ```
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
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``` What are common causes of ..... lesions? Spinal root/spinal nerve Peripheral nerve Brachial plexus Lumbosacral plexus ```
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
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
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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)
307
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 ```
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)
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Describe the sympathetic nerves of the ANS?
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
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What do connections between ganglia (of sympathetic nerves) allow?
Mass activation
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What acts as a modified ganglion? What is it made up of?
Adrenal medulla Only one neurone (EXCEPTION) Made up of secretory chromaffin cells innervated by pre-ganglionic fibres
311
Why does the adrenal medulla contribute to a generalised effect (sympathetic nerves, ANS)?
Produces catecholamines (released directly into the bloodstream-> generalised effect)
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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)
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Define: Dual innervation
Most viscera receive nerve fibres from parasympathetic and sympathetic divisions Organs not normally innervated equally by both divisions
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Define: Autonomic tone
Background rate of activity of the ANS | Balance between sympathetic and parasympathetic tone
315
How is the ANS involved in regulating blood pressure?
Baroreceptors
316
What are baroreceptors?
Arterial stretch receptors that detect high blood pressure | Found in the heart (carotid sinus and aortic arch)
317
What are the 2 main formulae for cardiac output?
``` CO = SV x HR CO= MABP/TPR ``` NB. TPR inversely proportional to radius4 so radius x 2-> TPR x 16
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Define: Cardiac output
The amount of blood pumped per unit time
319
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
320
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
321
How is mean arterial blood pressure controlled?
Increased sympathetic activity -> increased CO and increased TPR MABP= CO x TPR so this increases MABP
322
What leads to vasodilation (ANS-related)?
Vasodilation mainly due to decreased sympathetic tone
323
How does the sympathetic nervous system increase oxygen delivery to lungs
Via noradrenaline/adrenaline from the adrenals
324
List examples of ANS neurotransmitters
Acetylcholine Noradrenaline Adrenaline
325
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) ```
326
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
327
Describe the reuptake of noradrenaline
Degradation (COMT) Uptake (back into presyn terminal)-> metabolites ENZYME= MAO
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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
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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 Increased respiration Increased awareness ```
330
What is the acute stress response?
Stress acts on the hypothalamus and brainstem-> catecholamine release from adrenal medulla (via sympathetic NS)
331
What does the acute stress response lead to?
``` Tachycardia Splanchic bed vasocontriction Increased metabolic rate Sweating Pupil dilation Increased blood glucose concentration Increase mental alertness ```
332
What feeds into the hypothalamus to prompt action by the medulla (-> parasympathetic and sympathetic activity)?
Higher brain centres | Homeostatic changes
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Define: Thoracolumbar outflow
The preganglionic fibres of the sympathetic system | Found in T1-T12 and L1-L3 spinal nerves
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Define: Craniosacral outflow
The preganglionic fibres of the parasympathetic system | Found in cranial nerves and sacral spinal nerves
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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
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Define: Plexus
A network of nerve fibres originating from different levels associated with an organ e.g. the cardiac plexus
337
Sympathetic anatomy: Where are the preganglionic neurones found?
Lateral column GM of SC | T1-L3
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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)
339
Sympathetic anatomy: How are postganglionic fibres distributed to effector organs
Via grey rami comunicantes
340
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
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What sympathetic plexuses are found in the cervical region?
Plexus around pharynx Cardiac plexus Thyroid plexus Pulmonary plexus
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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
343
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 *Trick Q*
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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
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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
346
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
347
``` What is the associated parasympathetic ganglion of: CN3 CN7 CN9 CN10 ```
``` 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
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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
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How do baroreceptors respond predominantly to stretch of blood vessels (due to BP)?
Modified nerve endings of baroreceptors in carotid sinus and aortic arch
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When stimulated, what do baroreceptors signal to?
Medulla | Which then passes signal to sympathetic ganglia of the ANS
351
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
352
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
353
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
354
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
355
What blood pressure changes occur when standing upright?
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
What is postural hypotension caused by?
Impaired autonomic (mostly sympathetic) nerve response ``` This causes: Little change in CO No increase in TPR Acute reduced sympathetic response Postural hypotension ```
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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)
358
Describe the pupillary light reflex
Largely parasympathetic Pupil constricts in response to light Consensual reflex Involves: Iris Photosensitive photoganglion cells Edinger Westphal nuclei
359
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)
360
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)
361
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
362
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)
363
What does it mean if the only 1 eye constricts when light is shone on 1 eye?
Problem with motor function after the EW nuclei