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What is the Autonomic Nervous System?
The autonomic nervous system (ANS) is the division of the body’s nervous system which controls the involuntary functions of the internal organs, blood vessels and glands. Examples include heart rate, blood pressure, digestion and pupil diameter. It is separate from the somatic motor system, which controls skeletal muscle and deals with voluntary actions.
The autonomic nervous system primarily controls involuntary motor output to organs, but it also includes visceral afferent (incoming sensory) fibres from the internal organs, or viscera. These fibres carry sensory information to the central nervous system, where it is integrated largely within the brainstem and hypothalamus.
The autonomic nervous system has three divisions: sympathetic, parasympathetic and enteric. The enteric nervous system is a network of neurones that mainly regulates digestion and can work independently of the brain and spinal cord. This article covers the other two divisions:
- Sympathetic Nervous System (SNS): responsible for the ‘fight or flight’ response, triggered by stressful situations.
- Parasympathetic Nervous System (PNS): regulates the body’s routine, resting activities (‘rest and digest’).
Organisation of the Autonomic Nervous System
The division of the ANS into the sympathetic and parasympathetic systems is based on where the nerves leave the central nervous system (the two systems also differ in their neurotransmitters and actions, described below):
- SNS: arises from the thoracic and lumbar divisions of the spinal cord (thoraco-lumbar outflow).
- PNS: arises from the brainstem and sacral spinal cord (cranio-sacral outflow).
Remember the nervous system is bilaterally symmetrical, so when considering one side it is important to appreciate that the same is happening on the other side.
Diagram - The basic anatomy of the autonomic nervous system
SimpleMed original by Dr. Joshua Bray
Put simply, each autonomic pathway is a chain of two neurones: a myelinated pre-ganglionic and an unmyelinated post-ganglionic neurone. A ganglion is a collection of neurone cell bodies and is where the pre-ganglionic neurone synapses onto the post-ganglionic neurone.
In the sympathetic nervous system:
- The pre-ganglionic neurone is relatively short and normally synapses within a specialised chain of sympathetic ganglia adjacent to the vertebral column. This is known as the sympathetic chain (or paravertebral chain).
- The post-ganglionic neurone is relatively long and exits the sympathetic chain to travel to the target tissue.
In the parasympathetic nervous system:
- The pre-ganglionic neurone is relatively long and travels along cranial nerves (e.g. vagus nerve). If it arises from the sacral cord, it travels in the pelvic splanchnic nerves (nerves that carry these fibres to the pelvic organs). These pre-ganglionic neurones synapse close to or even within the wall of the target tissue.
- The post-ganglionic neurone is consequently relatively short.
Actions of the Autonomic Nervous System
As covered in previous articles, neurones communicate with other cells at synapses, where they release a neurotransmitter which activates receptors on the post-synaptic membrane.
All pre-ganglionic neurones (both sympathetic and parasympathetic) use acetylcholine (ACh) as their neurotransmitter. The acetylcholine acts on nicotinic acetylcholine receptors (a type of ACh receptor that nicotine also activates) on the membrane of the post-ganglionic neurone.
For post-ganglionic neurones, the use of neurotransmitter differs between sympathetic and parasympathetic divisions:
- Most sympathetic post-ganglionics release noradrenaline, which acts on adrenoceptors (receptors for noradrenaline and adrenaline) on the membrane of the target cell. The main exception is the supply to sweat glands, where the post-ganglionic neurones release ACh instead.
- Parasympathetic post-ganglionics release ACh, which acts on muscarinic acetylcholine receptors (the other main type of ACh receptor, named after the mushroom toxin muscarine) on the membrane of the target cell.
Adrenoceptors and muscarinic receptors are examples of G-protein coupled receptors (GPCRs: receptors that work by activating a G-protein, a signalling protein inside the cell). For more information, check out our article on G-Protein Coupled Receptors.
Diagram - The communication between pre- and post-ganglionic neurones of the autonomic nervous system
SimpleMed original by Dr. Joshua Bray
Stimulation of the sympathetic nervous system can result in:
Table - The physiological actions of the sympathetic nervous system
SimpleMed original by Dr. Joshua Bray
Stimulation of the parasympathetic nervous system can result in:
Table - The physiological actions of the parasympathetic nervous system
SimpleMed original by Dr. Joshua Bray
Role of Adrenaline in the Sympathetic Nervous System
As well as its neural component, the ‘fight or flight’ response also has an endocrine component: adrenaline.
Adrenaline is a hormone made from the amino acid tyrosine. It is secreted into the bloodstream by chromaffin cells, located within the medulla (inner part) of the adrenal glands. Chromaffin cells are essentially modified sympathetic post-ganglionic neurones. They secrete adrenaline (and some noradrenaline) into the blood, rather than releasing noradrenaline onto a target cell.
Adrenaline acts on the same adrenoceptors as noradrenaline, although the two bind some receptor types with different strengths. Because adrenaline is released into the bloodstream, it reaches the whole body and has a much more systemic (body-wide) effect than noradrenaline released at a single synapse, which contributes to the ‘fight or flight’ response.
Some tissues bind circulating adrenaline much more strongly than noradrenaline (they have a higher affinity for it). These tissues include the smooth muscle of the small airways (the bronchioles) and the smooth muscle in the walls of the arterioles (small arteries) that supply skeletal muscle. Acting on beta-2 adrenoceptors in these tissues, adrenaline widens the airways and increases blood flow to skeletal muscle.
For more information, check out our Endocrinology article on Adrenal Glands and Adrenal Disorders.
Diagram - Adrenaline biosynthesis from the amino acid, tyrosine
Creative commons source by Michael Skovbo Windahl [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Drugs Affecting the Autonomic Nervous System
Drugs targeting the autonomic nervous system are often used to bring about a therapeutic effect. These drugs exert their effects by interacting with post-synaptic receptors or by interfering with neurotransmitter metabolism.
Common drugs targeting the SNS:
- Beta Agonists (e.g. salbutamol): these drugs activate beta adrenoceptors. They are used in the treatment of asthma as they cause bronchodilation (widening of the airways) via beta-2 adrenoceptor stimulation. However, as a side effect, beta agonists can cause tachycardia (a fast heart rate) or palpitations (awareness of the heartbeat) due to stimulation of beta adrenoceptors in the heart. The human heart has both beta-1 and beta-2 adrenoceptors, and stimulating either type increases heart rate. These side effects are reduced, but not removed, when the drug is given by inhalation rather than by mouth or injection. NICE asthma guidance (NG245, 2024) says that a short-acting beta agonist such as salbutamol should not be prescribed for asthma without an inhaled corticosteroid (a steroid inhaler that reduces inflammation in the airways).
- Beta Blockers (e.g. atenolol, bisoprolol): these drugs act by antagonising (blocking) beta-1 adrenoceptors in the heart, resulting in reduced heart rate and contractility (the force of each heartbeat). They are used in angina (chest pain caused by reduced blood flow to the heart muscle) and in some cardiac arrhythmias (abnormal heart rhythms). Bisoprolol is also used in chronic heart failure. For hypertension (high blood pressure), NICE recommends other types of medicine before a beta blocker. Beta blockers can cause bronchoconstriction (narrowing of the airways) by blocking beta-2 adrenoceptors in the lungs. They should therefore usually be avoided in people with asthma. Non-selective beta blockers (which block beta-2 as well as beta-1 receptors) are contraindicated in asthma, which means they must not be used. Even cardioselective beta blockers (such as atenolol, which mainly blocks beta-1 receptors) are used in asthma only if there is no alternative, with caution and under specialist supervision.
- Alpha Blockers (e.g. doxazosin): these drugs cause smooth muscle relaxation by antagonising alpha-1 adrenoceptors. They are used in the treatment of benign prostatic hyperplasia (non-cancerous enlargement of the prostate). Less often, they are used as an add-on treatment for resistant hypertension (high blood pressure that stays high despite three other medicines). However, a common side effect of these drugs is postural hypotension (a drop in blood pressure on standing). This is due to interference with the baroreceptor reflex (the reflex that keeps blood pressure steady when you change position).
Common drugs targeting the PNS:
- Acetylcholinesterase Inhibitors (e.g. donepezil): these drugs enhance the effects of acetylcholine by inhibiting its breakdown by acetylcholinesterase (AChE). Donepezil is used to treat mild to moderate Alzheimer’s disease (a type of dementia). Pyridostigmine is used to treat myasthenia gravis (an autoimmune disease that causes muscle weakness). Pyridostigmine mainly targets the neuromuscular junction (where a motor nerve meets a skeletal muscle), which is part of the somatic motor system. These drugs can cause nausea, vomiting and diarrhoea at normal doses, and parasympathetic overload (SLUDGE syndrome) if the dose is too high.
- Muscarinic Agonists (e.g. pilocarpine, bethanechol): these drugs are rarely used in clinical practice due to a relative lack of selectivity and therefore a very high risk of systemic side effects (SLUDGE syndrome). However, there are some uses. Pilocarpine eyedrops (applied directly to the eye) are used to treat some types of glaucoma (raised pressure in the eye that can damage the optic nerve). Bethanechol is taken by mouth, so it acts throughout the body rather than locally. It can be used under medical supervision to stimulate bladder emptying in urinary retention (being unable to empty the bladder), although the BNF lists it as less suitable for prescribing.
- Muscarinic Antagonists (e.g. atropine, tiotropium): atropine is used to reverse bradycardia (a slow heart rate) that is causing problems such as low blood pressure. It antagonises (blocks) the M2 receptors (a subtype of muscarinic receptor) in the heart, which increases heart rate. Inhaled antimuscarinics such as tiotropium are used to treat chronic obstructive pulmonary disease (COPD, long-term narrowing of the airways). They are also used as an add-on in asthma that is not controlled on other treatment. They cause bronchodilation by blocking M3 receptors (another subtype of muscarinic receptor). A common side effect of antimuscarinics is a dry mouth, due to their inhibitory effect on saliva secretion.
Overstimulation of muscarinic acetylcholine receptors can lead to parasympathetic overload, otherwise known as SLUDGE syndrome, which can be life-threatening if not recognised and treated promptly. This is a medical emergency comprising the following symptoms:
- Salivation
- Lacrimation (tear production)
- Urinary incontinence
- Defecation
- Gastrointestinal upset
- Emesis (vomiting)
Causes of SLUDGE syndrome include drug overdose (e.g. pyridostigmine), ingestion of wild mushrooms that contain the toxin muscarine (such as Inocybe and Clitocybe species, not ‘magic mushrooms’), exposure to organophosphorus insecticides (chemicals that block acetylcholinesterase) or inhalation of nerve gas. Management includes supportive care (such as clearing the airway and removing bronchial secretions) and intravenous antimuscarinics, such as atropine. In poisoning with organophosphorus insecticides or nerve agents, atropine is repeated until the chest is clear (the bronchial secretions have dried up), the heart rate is above 80 beats per minute and the systolic blood pressure (the higher of the two readings) is above 80 mm Hg. The BNF also lists flushed, dry skin and dilated pupils as signs that enough atropine has been given. Pupil size is a poor guide, because it lags behind the other signs, and very dilated pupils suggest that too much atropine has been given. Pralidoxime, a drug that reactivates acetylcholinesterase, is added in moderate or severe poisoning.
Reviewed by: Dr. Thomas Burnell
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