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11.9 — The Autonomic Nervous System
You have never once decided to digest a meal, adjust your pupil size, or change the diameter of a blood vessel in your leg. The autonomic nervous system does all of it, continuously, and the only time you notice it is when it produces something dramatic — a racing heart before a presentation, a dry mouth, a faint, or the sudden nausea of a shock.
It is also the target of a very large share of all prescribed drugs, which is the main practical reason to understand it. Beta-blockers, inhalers, blood pressure drugs, bladder drugs, eye drops, antihistamines and most emergency drugs all act here.
Two divisions
Sympathetic — "fight or flight". Prepares the body for exertion or threat.
Parasympathetic — "rest and digest". Conserves energy and runs maintenance.
Most organs receive both, in opposition, which gives fine control in both directions — the same antagonistic pair principle as insulin and glucagon (Chapter 4.7).
A few receive only one. Blood vessels have essentially only sympathetic supply, which is why vasodilation is achieved by reducing sympathetic tone rather than by an opposing nerve, and why there is no parasympathetic drug for blood pressure. Sweat glands, the adrenal medulla and the muscles that raise hairs are also sympathetic only.
And they are not simply on or off. Both run continuously at a background level — autonomic tone — and control is by adjusting the balance. Your resting heart rate of 70 reflects a heart with an intrinsic rate near 100 being continuously restrained by the vagus (Chapter 7.3).
The anatomy
Every autonomic pathway uses two neurons in series, with a synapse in a ganglion between them. This differs from the somatic system, where one motor neuron runs from cord to muscle directly.
Sympathetic — fibres leave the cord from T1 to L2 only, hence "thoracolumbar outflow".
They synapse in a chain of ganglia running alongside the spine, close to the cord. So sympathetic fibres are short before the ganglion and long after it.
That arrangement allows one signal to spread widely. A single preganglionic fibre may synapse with 20 or more postganglionic neurons at several levels. The sympathetic system is built to produce a coordinated whole-body response, which is exactly what a threat requires.
Parasympathetic — fibres leave from the brainstem (cranial nerves III, VII, IX and X) and from the sacral cord (S2 to S4). Hence "craniosacral outflow".
They synapse in ganglia close to or within the target organ. So parasympathetic fibres are long before the ganglion and short after it.
And that allows precise, localised control. The parasympathetic system can slow the heart without affecting the gut.
The vagus alone accounts for around 75 percent of all parasympathetic activity, supplying the heart, lungs, and the gut down to about two thirds of the way along the colon (Chapter 11.7).
The transmitters, and why the drugs follow
Two transmitters, four receptor situations. Getting this straight makes an entire chapter of pharmacology fall into place.
All preganglionic neurons, in both divisions, release acetylcholine onto nicotinic receptors.
Parasympathetic postganglionic neurons release acetylcholine onto muscarinic receptors on the target organ.
Sympathetic postganglionic neurons release noradrenaline onto adrenergic receptors.
With two exceptions worth knowing. Sweat glands are sympathetic but use acetylcholine — which is why anticholinergic drugs cause dry skin and why they are used for excessive sweating. And the adrenal medulla is a modified sympathetic ganglion (Chapter 4.4) that releases adrenaline directly into the blood instead of onto a target.
That last point explains the difference between a nerve response and a hormonal one. The sympathetic nerves act in a second and stop in seconds; the adrenal medulla's adrenaline circulates for minutes. This is why the racing heart of a fright settles quickly but the shakiness lasts several minutes.
The adrenergic receptors
Four subtypes, and each has a drug class attached.
Alpha-1 — on blood vessels, the bladder neck and the prostate. Constriction.
- Agonists (phenylephrine) constrict vessels — used in decongestants and eye drops.
- Blockers (doxazosin, tamsulosin) relax vessels and the bladder neck — used in hypertension and prostate symptoms. Their main side effect, dizziness on standing, is the same action in the wrong place.
Alpha-2 — mainly on the presynaptic terminal, reducing further noradrenaline release. A negative feedback brake.
- Agonists (clonidine) therefore reduce sympathetic outflow, lowering blood pressure — which is counter-intuitive until you notice which side of the synapse they act on.
Beta-1 — mainly on the heart. Increases rate and force.
- Blockers (bisoprolol, metoprolol) slow the heart and reduce its work.
Beta-2 — on airway smooth muscle, uterus, and some blood vessels. Relaxation.
- Agonists (salbutamol) open the airways — every asthma inhaler.
And this is why beta-blocker selectivity matters clinically. A non-selective beta-blocker such as propranolol blocks beta-2 as well, constricting the airways — which can be dangerous in asthma. Cardioselective blockers are preferred, though the selectivity is relative rather than absolute.
Beta-3 — on bladder muscle and on fat cells. A beta-3 agonist is used for overactive bladder (Chapter 10.5).
Salbutamol's side effects are simply beta-2 receptors elsewhere. Tremor, from beta-2 receptors on skeletal muscle. And a fall in blood potassium, because beta-2 stimulation drives potassium into cells — which is exactly why salbutamol is used as an emergency treatment for hyperkalaemia (Chapter 10.3).
The muscarinic receptors
Blocked by "anticholinergic" drugs, and the side effect list is entirely predictable from the parasympathetic functions being removed.
Blocking the parasympathetic gives: dry mouth, blurred vision and dilated pupils, constipation, urinary retention, a faster heart, dry skin — and confusion, because muscarinic receptors are also central to memory (Chapter 11.2).
The traditional description — "dry as a bone, blind as a bat, red as a beet, mad as a hatter, hot as a hare" — is crude and it is an accurate list of anticholinergic poisoning, seen in overdose of tricyclic antidepressants, some antihistamines and deadly nightshade.
And this is why anticholinergic burden matters so much in older people. Many common drugs have mild anticholinergic activity — some antihistamines, bladder drugs, tricyclics, some antipsychotics — and several together can cause confusion, falls and constipation. Reviewing that burden is one of the highest-yield interventions in prescribing for older adults.
Atropine blocks muscarinic receptors, which is why it is used to speed a dangerously slow heart and to dry secretions, and why it is the antidote to organophosphate poisoning (Chapter 6.2).
What each division does
| Organ | Sympathetic | Parasympathetic |
|---|---|---|
| Heart | Faster, stronger | Slower |
| Airways | Dilate (beta-2) | Constrict |
| Pupil | Dilate | Constrict |
| Salivary glands | Thick scanty saliva | Copious watery saliva |
| Gut | Slows motility | Increases motility |
| Bladder | Relaxes; closes neck | Contracts; opens |
| Liver | Releases glucose | — |
| Skin vessels | Constrict | — |
| Muscle vessels | Dilate | — |
| Sweat glands | Sweating | — |
| Genitals | Ejaculation | Erection |
Two rows deserve comment.
The sympathetic dilates the pupil and the parasympathetic constricts it, which is why fear and excitement widen the pupils, and why bright light narrows them (Chapter 11.4).
And the genital row is the origin of the crude but genuinely used teaching phrase "point and shoot" — parasympathetic for erection, sympathetic for ejaculation. It explains why anxiety impairs erection, since sympathetic activation opposes it, and why several classes of drug affect the two differently.
The fight-or-flight response
A coordinated whole-body change, and every element makes sense as preparation for physical exertion.
Heart rate and force increase, raising cardiac output. Blood is redirected — away from the gut and skin, toward muscle, heart and brain. Airways dilate, increasing air flow. Pupils dilate, admitting more light and increasing peripheral awareness. The liver releases glucose, and fat cells release fatty acids. Sweating begins, anticipating heat production. Clotting is enhanced, reducing blood loss from injury. Digestion stops, since it is not the priority.
Two of these produce experiences worth explaining.
Blood diverting away from the skin is why fear makes you pale, and why the hands go cold.
And the dry mouth of nerves is the salivary glands switching from watery parasympathetic secretion to thick scanty sympathetic secretion (Chapter 9.1). It is not dehydration.
The system evolved for physical threats and is triggered by psychological ones, which is the mismatch problem of Chapter 3.6. A deadline produces the same physiological preparation as a predator, without the running that would resolve it. Chronic activation contributes to hypertension, impaired digestion and disturbed sleep, and Volume VI takes this further.
And the parasympathetic has its own dramatic response. The vasovagal reaction — a surge of vagal activity with a simultaneous fall in sympathetic tone to the vessels — slows the heart and drops the blood pressure, and the person faints.
Triggered by pain, the sight of blood, prolonged standing, heat, or emotional shock.
Lying the person flat and raising the legs restores cerebral perfusion immediately, because the heart no longer has to pump uphill. Sitting a fainting person up, or holding them upright, is exactly wrong and is a common and harmful instinct.
The warning signs — feeling hot, nauseated, seeing the vision grey out, hearing sounds recede — give a few seconds to lie down, and knowing them prevents most of the injuries that fainting causes.
Autonomic dysfunction
Orthostatic hypotension — the failure of the baroreflex on standing, covered in Chapter 7.6. Common, disabling, and frequently drug-induced.
Autonomic neuropathy — most often from diabetes, and it produces a scattered set of problems that are rarely connected to each other by the patient.
Postural dizziness. Gastroparesis with nausea and unpredictable blood sugars (Chapter 9.2). Constipation or diarrhoea. Bladder problems. Erectile dysfunction, which is frequently the earliest sign. Reduced sweating in the feet with compensatory sweating elsewhere. And a heart rate that does not vary — loss of the normal beat-to-beat variation, which is itself a marker of poor prognosis.
And the most dangerous consequence: silent ischaemia. The pain of angina and heart attack is carried by autonomic afferents, so autonomic neuropathy blunts it (Chapter 7.7). A person with diabetes may have a heart attack with no chest pain at all, presenting instead with breathlessness or simply feeling unwell.
Horner's syndrome — loss of sympathetic supply to one side of the face. Three signs: a drooping eyelid, a small pupil, and reduced sweating on that side.
Its value is entirely in what causes it, because the sympathetic pathway to the eye takes a long and specific route — down from the hypothalamus through the brainstem and cord to T1, then up through the neck alongside the carotid artery.
So Horner's syndrome localises to somewhere along that path, and the causes include a stroke in the brainstem, a tumour at the lung apex pressing on the T1 root, a carotid artery dissection, and neck trauma.
A painful Horner's syndrome of sudden onset is a carotid dissection until proven otherwise, and that is a stroke risk needing urgent imaging.
Postural orthostatic tachycardia syndrome (POTS) — a large rise in heart rate on standing without a large drop in blood pressure, with dizziness, palpitations and fatigue. Predominantly affects young women, is frequently dismissed, and is genuinely disabling. Management includes increased salt and fluid intake, compression garments, graded exercise starting in a reclined position, and sometimes drugs.
Deliberate influence
The autonomic system is not entirely involuntary, and this is more than folklore.
Slow breathing genuinely increases vagal tone. Breathing at about six breaths per minute produces the largest increase in heart rate variability, and the effect is measurable rather than merely subjective. It is the physiological basis of most breathing-based relaxation techniques.
The dive reflex — cold water on the face — slows the heart within seconds (Chapter 8.6), and it is used clinically to terminate fast rhythms.
Valsalva manoeuvres do the same (Chapter 7.4).
And biofeedback works, at least for some measures: people given real-time information about their own heart rate variability or skin conductance can learn to shift them.
What is oversold is the extent of the control. Claims that the autonomic system can be trained to cure disease run far ahead of the evidence, and the honest position is that a real and useful modest effect exists and is frequently exaggerated.
What the next page fixes
The brain and cord are extraordinarily fragile and are protected by an unusual set of arrangements. Chapter 11.10 covers the meninges, the cerebrospinal fluid, the blood supply and the blood–brain barrier — and why meningitis presents the way it does.