Flashcards in Week 110 - Peripheral Neuropathy Deck (68)
What are the spaces on the axon between myelination called?
Nodes of Ranvier
What are the signs and symptoms of motor neuropathy?
Weakness, Wasting, Muscle fasciculation, loss of reflexes.
What are the signs and symptoms of sensory neuropathy?
anaesthesia, paraesthesia, burning, hypersensitivity, ataxia (loss of proprioception), ulcers, areflexia.
What are the signs and symptoms of autonomic neuropathy?
Dry mouth, dry eyes, orthostatic hypotension, loss of heart rate variability, GI disturbance, bladder urgency/frequency, impotence, dry skin/ excess sweating, pupil reactions.
What are the three main types of peripheral nerve damage?
Axonal neuropathy, demyelinating and axonotmesis.
What change would you get in conducting velocity in a demyelinating neuropathy?
What changes would you get to the conducting velocity and compound motor action potential in an axonal neuropathy?
Normal CV but a slow CMAP.
Which type of neuropathy tends to be demyelinating and which tend to be axonal?
Inflammatory neuropathies tend to be demyelinating whilst chronic conditions tend to be axonal.
What is the likely cause of a mononeuropathy?
How does compression cause damage to a nerve?
Conduction velocity is slowed or blocked, the AP may also be dispersed. Damage is also caused to the myelin.
What are the symptoms and signs of carpal tunnel syndrome?
Numbness - waking at night, lateral 3 1/2 fingers.
Weakness - Thumb abduction
Wasting - Thenar eminence
What are the treatment options for carpal tunnel syndrome?
Wrist splints, injection of steroids.
Carpal tunnel decompression.
A man presents with 3/7 h/o of sensory loss in hands and feet, has progressively got weaker and can't lift arms above head, bladder and bowel function is normal. What is the likely diagnosis?
Guillain Barre Syndrome.
What is Guillain Barre Syndrome?
An acute, demyelinating, polyridiculo neuropathy, with preceding infection, vaccination, trauma, surgery. (Inflammation of spinal roots)
What are the investigations for Guillain Barre Syndrome?
Lumbar puncture - high level of protein will indicate inflammation.
Never conduction studies - show reduced CV and AP delayed and dispersed.
What are the treatment options for Guillain Barre Syndrome?
Intravenous immunoglobin - probably blocks pathogenic antibodies but reactions are relatively common, expensive and there is a world wide shortage.
Plasma exchange - Washes out pathogenic antibodies, venous access may be restricted, electrolyte disturbances common, BP fluctuations common.
A lady presents with numbness and burning sensation in her feet to the ankles it has progressed over the last few years, she is a controlled type II diabetic. What is the likely diagnosis?
Chronic diabetic neuropathy.
What are some of the aetiologies of chronic peripheral neuropathy?
Idiopathic, diabetes, drugs (statins,cytotoxic drugs) B12 deficiency, Alcohol, Inherited.
At resting membrane potential where are the higher concentrations of Na, K and Cl.
Na and Cl are at higher concentrations outside of the cell. K is at higher concentration inside the cell.
How does the membrane of a nerve cell maintain the resting potential?
A pump, using ATP, exchanges 3 Na out of the cell and brings 2 K into the cell.
What if the resting potential of a neurone?
What triggers an action potential?
A neurotransmitter binds to a ligand-gated channel allowing sodium to enter the cell.
What is the threshold potential and what is its value in mV?
The threshold potential is the level of depolarisation that is required to open voltage-gated Na channels, it is followed by the rising phase of an action potential. It has a value between 40-55mV.
At which point to the rising phase of an action potential end?
At approximately +40mV the Na channels close so no more Na can enter the cell.
Explain the falling phase of an action potential.
Depolarisation of the membrane also opens K channels after a slight delay, there is now an eflux of K which begins to restore the resting membrane potential and there is a slight hyper=polarisation.
Why can an action potential not fire straight after a previous one?
The Na and K are in the wrong place, there is a period where this is restored by the ion exchanger, this period is called the refractory period.
What are the insulating cells of the central nervous system?
What are the insulating cells of the peripheral nervous system called?
Which disease is caused by the genetic mutation of Schwann cells?
Charcot Marie Tooth disease.
What occurs at the synapse when an action potential arrives?
Voltage gated Ca2+ gates open allowing an influx of calcium ions. This causes vesicles of neurotansmitter to exocytose. This then diffuses across the synaptic cleft and binds to receptors on the postsynaptic terminal which triggers an action potential.
How do we remove neurotransmitter from the synaptic cleft?
There are three main ways;
1) Enzyme in the cleft to breakdown excess.
2) Pumps in the presynaptic terminal to actively pump neurotransmitter back into the neurone.
3) Receptors on the presynaptic terminal help to control the release.
What are the two broad types of receptor that neurotransmitters act on?
Ionotropic and metabotropic.
What are Ionotropic receptors?
Receptors which, when a neurotransmitter binds, opens as a channel to allow the passage of ions. They act fast.
What are metabotropic receptors and how do they work?
Neurotransmitter binds to the metabotropic receptor which activates the associated G-protein, this then causes intracellular messengers to modulate the ion channels. These act more slowly than iontropic receptors.
What level does the sympathetic system arise from? And where are the ganglia located?
T1-L2, ganglia are located in the sympathetic chain.
What are the prevertebral ganglia of the sympathetic system named after?
Adjacent arteries, eg. Coeliac ganglia.
Which neurotransmitter do the preganglionic neurones of the sympathetic system release?
Which neurotransmitter do the postganglionic neurones of the sympathetic system release?
Noradrenaline (except in sweat glands which is Acetylcholine.
Where are the preganglionic cells of the parasympathetic located? (2 locations)
1) The brain stem (Many cranial nerves).
Known as craniosacral.
The parasympathetic nervous system uses acetylcholine as it's neurotransmitter, which receptor does it use at the ganglion and which receptor at the effector?
Ganglion - Nicotinic Acetylcholine receptor.
Effector - Muscarinic Acetylcholine receptor.
Which receptor and neurotransmitter does the sympathetic system use at the ganglion and at the effector?
Ganglion - Acetylcholine - Nicotinic
Effector - Noradrenaline - Adrenergic
What are the two main types of the Acetylcholine receptors?
Nicotinic and Muscarinic.
Nicotinic is a receptor type of which neurotransmitter? What type of receptor is it and where are they located?
Acetylcholine, Ionotropic, On postganglionic neurons of the parasympathetic and sympathetic nervous system and also at neuromuscular junctions.
Muscarinic is a receptor type for which neurotransmitter? What type of receptor is it and where is it located?
Acetylcholine, Metabotropic, On effector cells of the parasympathetic nervous system.
Which type of receptor does the adrenal medulla have?
Nicotinic, cells of the adrenal medulla are basically postganglionic neurones.
What is an agonist of nicotinic receptors? And what effect does this have?
Nicotine, increased HR and BP.
How many muscarinic receptor subtypes are there?
Where are M1,4&5 receptors found?
In the CNS.
Where are M2 receptors found?
Present on myocardium, smooth muscle and presynaptic sites.
Where are M3 receptors found?
Exocrine glands, vessels, iris sphincter muscles.
Name an agonist of muscarinic receptors.
Muscarine, found in poisonous mushrooms.
What is an antagonist of muscarinic receptors and what clinical use does it have?
Atropine, pupil dilation for eye exams.
What are the two major subtypes of adrenergic receptors?
Alpha and Beta.
Alpha are subtype of which receptor type? What are the forms of Alpha receptors?
Adrenergic, Alpha-1, Alpha-2
Alpha-1 are a type of which receptor? Where are they located? What are the effects of agonists and antagonists? Name one Alpha antagonist.
• Vascular smooth muscle, pupillary dilator muscle, prostate, heart.
• Agonists - treat hypotension.
• Antagonists - treat hypertension.
Alpha-2 are a type of which receptor? Where are they located? What are the effects of agonists and antagonists?
• CNS, platelets, nerve terminals, smooth muscle, fat cells.
• Agonists - treat hypertension.
• Antagonists - limited clinical application found.
Beta receptors are a subtype of which receptor? What are the different types?
Adrenergic, Beta 1-3
Which type of receptor are Beta1-3 and where is each type located?
• B1 - Heart
• B2 - Repiratory, uterine and vascular smooth muscle, skeletal muscle, liver.
• B3 - Fat cells
Name a B2 agonist and what is used to treat?
What is Salbutamol and what is it used for?
B2 agonist used in the treatment of asthma.
Name two B-antagonists, their use and which subtype they act upon.
• Timolol - non-specific - used to treat glaucoma.
• Bisoprolol - Beta-1 - used to treat hypertension and cardiac ischaemia.
How many subunits make up the nicotinic receptor?
The influx of what into the presynaptic terminal (of a neuromuscular junction) stops the release of acetylcholine?
Name three autoimmune diseases of the neuromuscular junction.
1) Lambert Eaton Myasthenic Syndrome
2) Myasthenia Gravis
What is LEMS and what is the pathophysiology?
Lamber Eaton Myasthenic Syndrome, an autoimmune disease of the neuromuscular junction, antibodies block the Ca2+ channels. Causes weakness of movement but enough APs can trigger an AP in the post-synaptic terminal.
What is Neuromyotonia?
An autoimmune disease of the neuromuscular junction, antibody against the voltage-gated K+ channels, Acetylcholine continually released causing stiffness and cramps.
What is Myasthenia Gravis?
Autoimmune disease in which antibodies are produced against most acetylcholine receptors. Causes fatiguable weakness in the yes, bulbar muscles, neck extension, respiratory failure and limb muscles.