Autonomic Nervous System Flashcards
What does the ANS do?
The ANS controls all vegetative (involuntary) functions e.g:
- heart rate
- blood pressure
- GI motility
- iris diameter
The ANS is separate from the voluntary (somatic) motor system.
It is entirely efferent (but is regulated by afferent inputs).
What are the two divisions of the ANS?
- The sympathetic division
- The parasympathetic division
Describe features of Parasympathetic nerves
- originate in the lateral horn of the medulla and sacral regions of the spinal cord
- have long myelinated pre-ganglionic fibres
- have short unmyelinated postganglionic fibres
- have ganglia that are located in the tissues innervated by the postsynaptic fibres
- have actions that (in general) oppose the sympathetic nervous system
Describe features Sympathetic nerves
- originate in the lateral horn of the lumbar and thoracic spinal cord
- have short myelinated pre-ganglionic fibres
- have long unmyelinated post-ganglionic fibres
- have ganglia that are located in the paravertebral chain close to the spinal cord
- have actions that (in general) oppose the parasympathetic nervous system
Describe neurotransmitters in the ANS
The principal (but by no means the only) neurotransmitters in the ANS are:
- All pre-ganglionic neurons are cholinergic i.e. they use ACh as their neurotransmitter
- Parasympathetic and sympathetic pre-ganglionic release of ACh results in the activation of post-ganglionic nicotinic ACh receptors
- Nicotinic ACh receptors are ligand-gated ion channels
- Parasympathetic post-ganglionic neurons are also cholinergic
- They release ACh which acts on muscarinic ACh receptors in the target (‘effector’) tissue
- Muscarinic ACh receptors are G-protein coupled receptors (GPCRs)
- Most sympathetic post-ganglionic neurons are noradrenergic i.e. they use noradrenaline (NA) as the principal neurotransmitter
- NA interacts with one of two major classes of adrenoceptors, a-adrenoceptors and b-adrenoceptors
- These can be further subdivided into a1 and a2 and b1, b2 and b3 subtypes
What are some exceptions to the general rules of neurotransmission in the ANS?
-Some specialized sympathetic post-ganglionic neurons are cholinergic, not noradrenergic e.g. those innervating sweat glands, hair follicles (piloerection)
-Other transmitters are found in the ANS
• Non-Adrenergic, Non-Cholinergic (NANC) transmitters • These may be co-released with either NA or ACh
Examples include:
- ATP
- nitric oxide (NO)
- 5-hydroxytryptamine (5HT; serotonin)
- neuropeptides (e.g. VIP (vasoactive intestinal peptide), substance P)
How do sympathetic postganglionic neurons in the adrenal medulla differ?
Sympathetic postganglionic neurons in the adrenal glands are different:
- They differentiate to form neurosecretory chromaffin cells
- Chromaffin cells can be considered as postganglionic sympathetic neurons that do not project to a target tissue
- Instead, on sympathetic stimulation these cells release adrenaline (US name: epinephrine) into the bloodstream
What are chromaffin cells?
-Chromaffin cells are present in the adrenal medulla
• Chromaffin cells are innervated by pre-ganglionic sympathetic neurons
Give a summary of neurotransmission in the ANS
What are the physiological consequences of parasympathetic stimulation?
What are the physiological consequences of sympathetic stimulation?
Describe afferent/sensory inputs to the ANS
- Sensory neurons monitor levels of CO2, O2 and nutrients in the blood, arterial pressure, and GI tract content and chemical composition
- Blood O2 (and CO2 , pH) are also directly sensed by the carotid body, chemoreceptors at the bifurcation of the carotid artery, relaying information to the CNS via the glossopharyngeal nerve
- Primary sensory neurons project on to “second order” sensory neurons located in the medulla oblongata, forming the nucleus tractus solitarius (nTS), that integrates all visceral afferent information
- The nTS also receives input from the area postrema, that detects toxins in the blood and the cerebrospinal fluid and is essential for chemically-induced vomiting and conditional taste aversion
- Sensory information constantly modulates the activity of the efferent neurons of the ANS
What are the basic steps of neurotransmission?
- uptake of precursors
- synthesis of transmitter
- vesicular storage of transmitter
- degradation of transmitter
- depolarization by propagated action
- potential
- depolarization-dependent influx of Ca2+
- exocytotic release of transmitter
- diffusion to post-synaptic membrane
- interaction with post-synaptic receptors
- inactivation of transmitter
- re-uptake of transmitter
- interaction with pre-synaptic receptors
How is acetylcholine synthesised?
How is acetylcholine degraded?
Describe cholinergic transmission
What are some therapeutic interventions affecting cholinergic transmission?
- Nicotinic acetylcholine receptors (nAChRs) at autonomic ganglia and the neuromuscular junction differ in structure. Therefore, some drugs have actions selectively at autonomic ganglia (e.g. the ganglion-blocking drug trimethaphan, which is used in hypertensive emergencies and to produce controlled hypotension during surgery).
- There are 5 muscarinic acetylcholine receptor (mAChR) subtypes (M1-M5), however, at present few subtype-selective mAChR agonists or antagonists are available clinically.
- Nevertheless, some newer agents do display limited tissue selectivity (e.g. the mAChR antagonist, tolterodine, which is used to treat “overactive bladder”).
- The actions of endogenously released ACh can also be enhanced by AChE inhibitors (e.g. pyridostigmine, used to treat myasthenia gravis; donepezil, used to treat Alzheimer’s disease).
What does the lack of selectivity of most cholinergic drugs mean?
A relative lack of selectivity of cholinergic drugs means that unwanted ‘side-effects’ often limit their usage.
For example, a non-selective, muscarinic ACh receptor agonist is likely to cause autonomic side-effects
What is sludge syndrome?
- massive discharge of the parasympathetic nervous system.
- the symptoms of “SLUDGE” are primarily due to chronic stimulation of muscarinic acetylcholine receptors, in organs and muscles innervated by the parasympathetic nervous system.
Salivation: stimulation of the salivary glands
Lacrimation: stimulation of the lacrimal glands
Urination: relaxation of the urethral internal sphincter muscle and detrusor muscle contraction
Defecation
Gastrointestinal upset: Smooth muscle tone changes causing GI problems, including diarrhoea
Emesis: Vomiting
An extension is SLUDGEM, where the additional M indicates:
• Miosis: stimulation of the pupillary constrictor muscles
What causes sludge syndrome, and how is it treated?
- One common cause of SLUDGE is exposure to organophosphorus insecticides (e.g. parathion), or nerve gases (e.g. sarin). These agents covalently-modify (phosphorylate) acetylcholinesterase, thereby irreversibly deactivating the enzyme and raising acetylcholine levels to cause SLUDGE(M).
- SLUDGE may be treated with atropine, pralidoxime, or other anticholinergic agents.
What are some clinical examples of drugs that affect cholinergic transmission?
Muscarinic ACh receptor agonists: pilocarpine and bethanechol are respectively used to treat glaucoma and acutely to stimulate bladder emptying.
Muscarinic ACh receptor antagonists: ipratropium and tiotropium are used to treat some forms of asthma and chronic obstructive pulmonary disease (COPD).
Tolterodine , darifenacin and oxybutynin are used to treat overactive bladder.
What are varicosities (post-ganglionic sympathetic neurons)?
Post-ganglionic sympathetic neurons generally possess a highly branching axonal network with numerous varicosities, each of which is a specialized site for Ca2+-dependent noradrenaline release
Describe the process of noradrenaline recycling
Describe noradrenaline transmission
Following Ca2+-dependent exocytotic release of NA:
- NA diffuses across the synaptic cleft and interacts with adrenoceptors in the post-synaptic membrane to initiate signalling in the effector tissue
- NA interacts with pre-synaptic adrenoceptors to regulate processes within the nerve terminal – e.g. NA release
- NA has only a very limited time in which to influence pre- and post-synaptic adrenoceptors as it rapidly removed from the synaptic cleft by noradrenaline transporter proteins
