Neurology Flashcards
What is frontal lobe for?
Responsible for executive functions such as personality
What is the parietal lobe for?
Contains the somatic sensory cortex responsible for processing tactile information
What is temporal lobe for?
Contains important structures e.g- hippocampus (short term memory), the amygdala (behaviour) and Wernicke’s area (auditory perception & speech)
What is occipital lobe for?
Processing of visual information
Where is the brainstem and what is its overall function?
Dorsal region of CNS
Role in motor coordination, balance and posture
Functions of astrocyte
Cell repair: synthesise neurotrophic factors
Abundant
Structural: form the blood brain barrier
Homeostasis: removal and reuptake of neurotransmitter
‘star’ shape
Other cells of the NS
Schwann cells: myelinate one axon, PNS
Oligodendrocytes: myelinate many axons, CNS
Microglial: immune cells, similar to macrophages
Ependymal: line ventricles containing CSF, regulate CSF production, important for blood-brain barrier
What are the relative concentrations of these ions extracellularly?
Higher Na+
Higher Cl-
Lower K+
Higher Ca2+ (High conc. gradient)
Define flux
The number of molecules that cross a unit area per unit time
Define electrochemical equilibrium
When electrical force prevents further diffusion across a membrane
What is the Nernst and GHK equation used to calculate?
Nernst: equilibrium potential for a single ion
GHK: resting membrane potential
p = permeability
Explain how the ions are involved in the generation of an action potential?
Influx of Na+ via voltage gated sodium ion channels (VGSC) leads to further depolarisation
Explain how the ions are involved in the restoration of the resting membrane potential?
Voltage gated potassium ion channels (VGKC) opens at slower rate, leading to efflux of K+ from cell which repolarises the membrane
Permeability to Na+ decreases, as VGSCs close
Permeability to K+ increases
How is the Na+/K+ ATPase involved in restoring the ion gradients?
Resting configuration - Na+ & K+ enters vestibule & upon phosphorylation, ions are transported through the protein against conc. gradient –> phosphorylation doesn’t take place until active configuration –> Na+ removed from cell
Active configuration - Na+ removed from cell and K+ enters the vestibule against conc. gradient. The pump returns to resting configuration and K+ is transported back into cell
What are graded potentials?
NOT all or nothing
Changes in membrane potential in response to stimulation –> occur at synapses to prevent initiation of APs
Charge leaks from axon as impulse propagates –> NO AP generated
What is the function of Myelin in the travelling of the AP?
Prevents AP spreading because it has high resistance and low capacitance
What happens when the action potential reaches the Synapse?
AP opens voltage gated Ca2+ channels (VGCC) at pre-synaptic terminal
Ca2+ influx down conc. gradient → exocytosis of vesicles containing neurotransmitter
Neurotransmitter released into synaptic cleft
Neurotransmitter binds to receptors on post-synaptic membrane
Receptors modulate post-synaptic activity
Enzymes (cholinesterase) break down neurotransmitter to be uptaken again by pre-synaptic cleft
Or the neurotransmitter could be recycled by transporter proteins on the pre-synaptic cleft
How does an action potential travel across a neuromuscular junction?
Action potential propagated along axon (Na+ and K+) → Ca2+ entry at presynaptic terminal
Ca2+ entry → ACh release into synapse
ACh binds to nicotinic ACh receptors (nAChR) on skeletal muscle → change in end-plate potential (EPP)
Miniature EPP: Quantal ACh release = small depolarisation caused by release of single vesicle of ACh into synaptic cleft
AP travels through T-tubules that are continuous with sarcolemma & closely connected to sarcoplasmic reticulum
What is the function of the sarcoplasmic reticulum and what effect does it have?
Ca2+ storage → Ca2+ release following sarcolemma depolarisation
Ca2+ → myofibril contraction & muscle contraction
Describe excitation-contraction coupling
- Once nACh receptor is activated, sarcolemma is depolarised
- AP travels down sarcolemma into T-tubules
- Depolarisation at T-tubules eventually causes Ca to be released from SR
- SR surrounds myofibrils –> Ca release causes muscle contraction
What is Myasthenia Gravis and what does it cause?
Autoimmune disorder: antibodies directed against ACh receptor
Symptoms: fatigable weakness (becomes more pronounced with repetitive use)
What is Botulism, Myasthenia Gravis + LEMS?
- disrupts ACh release
- disrupts ACh receptor (autoimmune)
- disrupts VGCS = fatigue, weakness, weight loss, mild facial muscle weakness
Describe the steps of an action potential
Resting membrane potential - Permeability K+> Permeability Na+
Depolarisation - Stimulus depolarises membrane potential to move it in positive direction towards threshold
Upstroke - VGSC open quickly so Na+ enters cell down electrochemical gradient. VGPC open slowly so K+ leaves cell down electrochemical gradient.
Membrane potential moves towards Na+ equilibrium potential
Repolarisation - Decreased permeability of Na+ as VGSC close. Increased permeability of K+ as VGPC open so K+ leaves cell down its electrochemical gradient
Membrane potential moves towards K+ equilibrium potential
After-Hyperpolarisation - At rest VGPC are still open and so K+ leaves cell down electrochemical gradient
Membrane potential moves closer to K+ equilibrium so some VGPC then close and membrane potential returns to resting potential
What is the absolute refractory period?
Period where inactivation gate of VGSC is closed
Impossible to generate another AP
BOTH activation and inactivation gates are closed
What is the relative refractory period?
Period of time where you need a stronger than normal stimulus to trigger another action potential
Due to hyperpolarisation, more of a depolarisation is required to reach threshold and then cause another action potential
Only activation gate is closed
What does the propagation distance and velocity of the AP along the axon depend on?
Myelin thickness - Linear relationship between conduction velocity and myelin thickness
Diameter of axon - Larger diameter, faster travelling of action potential due to less resistance (conduction velocity proportional to square root of axon diameter)
3 factors that influence movement of ions across membrane
- Conc. of ion on both sides of membrane
- Charge on ion
- Voltage across membrane
What are some causes of reduced conduction velocity?
REDUCED MYELINATION:
- Multiple sclerosis
- Guillian-Barre syndrome
- Cold
- Anoxia
- Compression
- Drugs
- Parkinson’s
REDUCED AXONAL DIAMETER:
- Regrowth after injury
What are the 3 types of post synaptic cells?
- Axodendritic
- Axoaxonic
- Axosomatic
Define drug
A chemical substance that interacts with a specific target within a biological system to produce a physiological effect
How can you determine the most safe drug based on the dosage of the drug?
The safest drugs are those where there is a large difference between the dose required to induce the desired effect and the dose required to induce side effects/adverse effects
4 main classes of proteins that drugs usually target?
Receptors
Enzymes
Transport Proteins
Ion Channels
What class of protein does Atorvastatin act on?
Enzyme - HMG CoA reductase
What class of protein does Citalopram act on?
Transport Protein - Serotonin re-uptake protein
What class of protein does Salbutamol act on?
Receptor - Beta-2 Adrenergic receptor in lung
What class of protein does Amlodipine act on?
Ion channel - Calcium channel
Define side effect
An effect produced by the drug that is secondary to the intended effect
As dose increases, selectivity…
decreases
Which kind of effect increases as dosage of a drug increases?
Off-target effects
EPILEPSY
- Causes
- Clinical features
- Symptoms
- traumatic brain injury, CNS infection, brain tumours, stroke, Alzheimer’s, prenatal injuries, family history
- abnormal taste, smell & touch sensations; deja vu; abdominal sensations
- Temporal lobe –> memory loss, speech production, smacking lips, picking at clothes
How focal seizure differ from general event? Why seizures develop?
localised brain activity which then leads to symptoms that typically seize 1 side of body or 1 specific body part
Imbalance between inhibitory + excitatory input within certain regions of brain
List 4 characteristics of synaptic transmission
Rapid timescale
Diversity
Plasticity
Learning and memory
What are the 3 steps that occur when a dendrite of one neurone receives an electrical impulse from another neurone?
Information reception at dendrites
Integration (occurs at the soma)
Rapid transfer (action potential) - impulse passed along axon towards the synaptic terminals
List 3 types of molecules that can be neurotransmitters and include examples of each
Amino acids - glutamate, gamma-aminobutyric acid (GABA), glycine
LAST 2 = Cl- influx, leads to hyperpolarisation
Amines - noradrenaline, dopamine, serotonin
Neuropeptides - enkephalins, opioid peptides
What is the single-most important excitatory neurotransmitter in the brain?
Glutamate
What is the single-most important inhibitory neurotransmitter in the brain?
GABA
Where is glycine most active and is it excitatory or inhibitory?
Spinal cord and brainstem
Inhibitory
Which neurotransmitter stimulates parasympathetic lacrimal gland secretion?
ACh - main NT in parasympathetic
- -> Nicotinic ion channel receptors (NMJ)
- -> Muscarinic G-protein coupled receptors
What are the methods by which the neurotransmitter can be returned to the pre-synaptic terminal after depolarising the post-synaptic terminal?
Re-uptake of neurotransmitter via a protein transport channel
Enzymatic degradation within the synaptic cleft (e.g. acetylcholine broken down by acetylcholinesterase)
What 2 things does neurotransmitter (NT) release require?
Calcium influx and RAPID transduction (electromechanical transduction - links the Ca2+ influx with NT release)
What type of proteins on the vesicle and presynaptic membrane enable fusion and exocytosis?
SNARE proteins (vesicular proteins e.g. synapsin, synaptobrevin, snap25)
What does the neurotoxin alpha larotoxin (from black widow spider) do?
Stimulate NT release until depletion of NT → muscular paralysis
What do Zn2+ dependent endopeptidases do?
Inhibits transmitter release
What does tetanus toxin cause and what bacteria produces it?
Causes spasms and paralysis as it inhibits GABA and glycine (both inhibitory in CNS)
Produced by Clostridium tetani
What does botulinum toxin cause and how does it do this?
Flaccid paralysis (due to complete muscle relaxation)
Cleaves peptide bonds of vesicular proteins leading to inactivation hence docking, fusion and release of NT can’t occur
One of the most powerful toxins
What responses do ion channel-linked receptors mediate? EXAMPLES
All FAST (msecs) excitatory and inhibitory transmission
CNS: glutamate, GABA, glycine
NMJ: nicotinic ACh receptors
What type of responses do G-protein coupled receptors mediate? EXAMPLES
SLOWer (secs/mins) than ion channel-linked receptors
CNS: serotonin, noradrenaline, neuropeptides, dopamine
Parasympathetic: muscarinic ACh receptors
Name the 2 main types of ion-channel linked glutamate receptors and what do they mediate?
AMPA - majority of FAST excitatory synapses. Rapid onset, offset and desensitisation. Only permeable to Na+
NMDA - SLOW component of excitatory transmission. Serve as coincidence detectors which underlie learning mechanisms. Permeable to both Na+ and Ca2+. Hippocampus has a very high density of these receptors
Outline the process that occurs at an excitatory glutamate synapse
Glutamate synthesised from glucose via TCA cycle and transamination. Loaded into vesicles and released into synaptic cleft via exocytosis
Glutamate reversibly binds postsynaptic receptors (AMPA and NMDA)
Inactivation of glutamate (re-uptake into presynaptic terminal) + can also be re-uptaken into surrounding glial cells.
Rapid uptake of glutamate by excitatory amino acid transporters (EAATs)
What happens when glutamate is in glial cells?
Glutamate is enzymatically modified by glutamine synthetase to glutamine, which can then be pumped back into the pre-synaptic terminal
What can abnormal cell firing associated with excess glutamate lead to?
Seizures
Shown by spikes on an EEG
Outline the process that occurs at an inhibitory GABA synapse
GABA synthesised in the pre-synaptic terminal by decarboxylation of glutamate by glutamic acid decarboxylase (GAD)
GABA reversibly binds to post-synaptic receptors (GABA a receptors) → opens chloride channels → influx of chloride ions into post-synaptic terminal leading to hyperpolarisation
Inactivated by rapid uptake into pre-synaptic terminal by GABA transporters (GATs)
OR GABA can be taken into glial cells where it is enzymatically modified by GABA-transaminase (GABA-T) to succinic semialdehyde
Which drugs facilitate GABA transmission?
Barbiturates
Benzodiazepines
Steroids
Convulsants
Zn 2+
Ethanol
What properties do drugs facilitating GABA transmission have?
Antiepileptic
Anxiolytic
Sedative
Muscle relaxant
What are special nerves for?
Special senses: hearing, vision, taste, smell, balance
4Ss: smiling, speaking, masticating, swallowing
SVE: innervation of skeletal muscle jaw, face, larynx, pharynx
Somatic vs visceral
Afferent vs efferent
skeletal muscle vs smooth muscle
Towards brain vs away from brain
Compression at the optic chiasm is most likely to affect which blood vessel?
Anterior Communicating Cerebral Artery
Where are the two spinal cord enlargements
CERVICAL: upper limbs innervation
LUMBAR: lower limbs innervation
What non-skeletal peripheral functions does the ANS control?
Cardiac muscle
Internal organs
Smooth muscle
Skin
What are the 2 afferent neurones of the sensory division?
Somatic sensory –> external stimuli, only skeletal muscles
Visceral sensory –> trunk organs, vessels, glands
If there is a high blood pressure, how is this information relayed to the relevant visceral motors and which of the PNS and SNS are switched on?
Visceral sensory - baroreceptors detect increase in pressure
Signal sent to the PNS to be sent to CNS
Signal sent from CNS to PNS to visceral motors
Parasympathetic nervous system switched on to reduce blood flow
Sympathetic nervous system switched off to prevent further increase in blood flow
Where is the autonomic sensory (afferent) information relayed to?
Hypothalamus
Where do visceral motor nuclei originate?
Hypothalamus
What is meant by a sympathetic (paravertebral) trunk?
Long chains running parallel to the spinal cord, with lots of sympathetic nerves coming out of the spinal cord will synapse within those sympathetic chains
Allows for mass activation, so lots of sympathetic neurons can be activated at the same time
Allows coordinated responses for flight or fight
What is the exception to the two neuron arrangement in the ANS?
Adrenal gland
Single sympathetic nerve that innervates the adrenal gland
What neurotransmitter does the Adrenal gland release?
Does not release neurotransmitter
Instead secretes hormone, Adrenaline (and some noradrenaline)
Into bloodstream
What is the name of the complex neural network within the gut?
Enteric NS - largely responds to gut function and stimuli received withing gut without engaging brain
How does sympathetic control occur in the lungs to initiate bronchodilation?
Adrenaline released from adrenal gland travels in the bloodstream and diffuses into the lung to cause bronchodilation that way
Describe the micturition reflex
Bladder slowly fills and moderate pressure in the bladder, SNS is in charge at this point
Internal sphincter controlled by SNS is closed off to prevent urine leaving the bladder
Once pressure gets to certain point, sensory information is relayed to the brain
PNS switched on and SNS is switched off
PNS contracts detrusor muscle to squeeze bladder and force urine out
Internal Sphincter is relaxed as SNS is turned off so urine can leave the bladder
What type of receptor is required at all autonomic ganglia?
Cholinergic (nicotinic acetylcholine) receptors
e.g, Ion channel receptors as they mediate all fast excitatory and inhibitory transmission
At the nerve innervating the Adrenal gland in the SNS, what receptor is found?
Nicotinic Acetylcholine (nACh) ion channel receptors
Where are the muscarinic G-coupled protein receptors found?
Post-ganglionic nerves of the PNS
Where are the adrenergic G-coupled protein receptors found?
Post-ganglionic nerves of the SNS
In the heart, what are the muscarinic and adrenergic receptors responsible for respectively?
Muscarinic - slowing down
Adrenergic - speeding up
Describe the action of Noradrenaline at a synapse?
Tyrosine converted to DOPA by tyrosine hydroxylase
This DOPA then converted to dopamine by DOPA decarboxylase
Dopamine packaged into vesicles with dopamine Beta hydroxylase and Noradrenaline is the product
Action potential causes Ca2+ influx and exocytosis
Exocytosis and neurotransmitter release
Receptor activation (Adrenergic)
Removal of neurotransmitter from synapse via uptake into pre-synaptic terminal or glial cell; can be metabolised in the synapse prior to uptake
What are the 2 enzymes that metabolise noradrenaline?
Monoamine oxidase A within pre-synaptic terminal
Catechol-O-methyltransferase (COMT) in glial cells
Describe the action of Adrenaline in the nerve innervating the Adrenal gland
Tyrosine converted to DOPA by tyrosine hydroxylase and DOPA converted to dopamine by DOPA decarboxylase
Dopamine packaged into vesicles with dopamine Beta hydroxylase, Noradrenaline is the product
Noradrenaline converted to adrenaline in the cytoplasm by phenylethanol methyltransferase
Action potential causes Ca2+ influx & Exocytosis
Exocytosis & Neurotransmitter release
Adrenaline diffuses into capillaries and is transported to tissues in the blood
