Week 110- Peripheral Neuropathy Flashcards
Resting membrane potential
-65mV
polarised at rest by the Na/K pump. Pumps Sodium out and Potassium in.
Two gradient forces: Chemical and Electrical
Action potential
Rising phase, falling phase, hyperpolarisaton.
Ligand gated Na channels open. Na in.
Opens Voltage gated Na channels.
Triggers rising phase. Voltage reaches 40mV.
Na channels close at peak of action potential.
Voltage gated K channels open and K rushes out.
Restore membrane potential.
Myelin
80% Lipid
20% protein
Allows faster conduction of action potential.
myelinated neurons= white.
Schwann cells- peripheral CNS
Oligodendrocytes- Central CNS
Multiple Sclerosis
Demylination of central nerves.
Guillan-Barre syndrome
– Inflammatory demyelination of peripheral nerves
– Progressive motor and sensory function loss
- Characterised by high protein in CSF
treatment:
- IV imunoglobulin
- Plasma washout (rarely used)
general:
Assess risk of VTE (heparin needed)
monitor Lung function and consult ITU if necessary
treat pain but avoid resp depressants
Charcot-Marie tooth disease
genetic mutation in Schwann cells.
Lambert-Eaton syndrome
Genetic condition where antibodies are raised against voltage gated Calcium channels.
gamma-Amino butyric acid (GABA) neurotransmitter.
Inhibitory neurotransmitter.
acts through ligand gated chloride channels to hyperpolarize neurone.
glycine neurotransmitter
Inhibitory neurotransmitter.
acts through ligand gated chloride channels to hyperpolarize neurone.
Central Nervous system
- sympathetic
- parasympathetic
- enteric
sympathetic system
arises T1-L2. Preganglionic neurons located lateral horn.
Sympathetic chains run length of spinal cord as paravertebral ganglia.
Origin of many postganglionic neurons.
Pass through the para-vertebral column without synapsing.
Sympathetic system- preganglionic neurones
– Short
– Myelinated
– Release Acetylcholine
– Connect with several (~ 10) postganglionic neurones
Sympathetic system- postganglionic neurones
Long
– Unmyelinated
– Release Noradrenaline
• except in sweat glands (acetylcholine)
Parasympathetic system- preganglionic neurones
Located either in brainstem (some cranial nerves) or S2-S4 segments of the spinal cord.
Ionotropic receptors
– Predominantly postsynaptic
– Conduct ions
– Which may also activate intracellular signalling pathways
– Act fast
Metabotropic receptors
(Do not conduct ions)
– Predominantly presynaptic
– Coupled to intracellular signalling pathways
– May also be coupled to ionotropic receptors
– Act (more) slowly
Sympathetic system- Neurotransmitters
Acetylcholine
Noradrenaline
Parasympathetic system- Neurotransmitters
Acetylcholine
Muscarinic Acetylcholine receptors on effector muscles
Acetylcholine
Nicotinic receptors – Ligand-gated channels – Excitatory – Multiple subtypes • Each receptor composed of 5 subunits • Each subunit may occur in multiple forms • Tissue-specific expression – On postganglionic neurons – Also neuromuscular junction • Muscarinic receptors – Metabotropic receptors - are NOT channels – On effectors of parasympathetic system • Except adrenal medulla which has nicotinic receptors
Adrenal Medulla
• Directly innervated by preganglionic neurons
• Cells of the adrenal medulla are basically
modified postganglionic sympathetic neurons
– Secrete noradrenaline and adrenaline
Atropine
Muscarinic antagonist.
Muscle relaxant, used to dilate pupil for eye exams.
Acetylcholinesterase as a drug target
Reversible inhibitors have clinical uses – Myasthenia gravis • Neostigmine, pyridostigmine – Glaucoma • Physostigmine, demecarium
irreversible inhibitors such as organophosphates very bad.
Adrenergic receptors
Alpha receptors- alpha-1 antagonist doxazosin (treat hypertension).
Beta receptors- Salbutamol B2 agonist
antagonists- timolol- non specific blocker used to treat glaucoma
Bisoprolol- selective B1 antagonist
Orthostatic/postural hypotension
Autonomic system doesn’t react quickly/enough to drop in blood pressure
when person stands up (from sitting)
– May be side effect of a1 adrenergic blockers
