Autonomic nervous system

Organisation of the two divisions

Every autonomic pathway uses two neurons: a preganglionic neuron in the brainstem or spinal cord and a postganglionic neuron in a peripheral ganglion. The hypothalamus is the highest integrating centre; the brainstem (nucleus tractus solitarius, dorsal motor nucleus of the vagus, nucleus ambiguus, rostral ventrolateral medulla) runs the moment-to-moment reflexes.

• All preganglionic fibres of both systems are cholinergic. Postganglionic sympathetic fibres synthesise noradrenaline; they do not make adrenaline (that needs phenylethanolamine-N-methyltransferase, found in the adrenal medulla).
• Parasympathetic cranial routes: III (ciliary ganglion: pupil, ciliary muscle); VII (pterygopalatine and submandibular ganglia: lacrimal, submandibular and sublingual glands, via chorda tympani); IX (otic ganglion: parotid); X (heart, lungs, gut to the distal transverse colon). Pelvic splanchnic nerves (S2–S4) supply the distal colon, rectum, bladder and erectile tissue.
• Sympathetic supply to the gut comes from thoracic splanchnic nerves: foregut from the coeliac ganglion (greater splanchnic, T5–T9); midgut, including the jejunum, from about T8–T10 through the greater and lesser splanchnic nerves and the superior mesenteric plexus.

Cholinergic and other exceptions

• Eccrine sweat glands are innervated by sympathetic postganglionic fibres that release acetylcholine on muscarinic (M3) receptors. This is the classic "sympathetic cholinergic" fibre. Apocrine glands (axilla) respond to circulating adrenaline.
• Adrenal medulla receives preganglionic sympathetic fibres directly; its chromaffin cells act as modified postganglionic neurons, releasing about 80% adrenaline and 20% noradrenaline into the blood in response to acetylcholine on nicotinic receptors.
• Renal and splanchnic vessels dilate to dopamine (D1).
• Arrector pili muscles (goosebumps on fear or cold) are supplied only by sympathetic adrenergic fibres acting on α1 receptors; there is no parasympathetic supply to skin, sweat glands, arrector pili or most blood vessels.
• Many parasympathetic and sympathetic fibres also release co-transmitters: nitric oxide and VIP (erection, gut sphincter relaxation), ATP and neuropeptide Y. Calcitonin gene-related peptide (CGRP), released from trigeminal sensory endings, is a powerful vasodilator in migraine; monoclonal antibodies against CGRP or its receptor are used for prevention.

Receptors and their effects

Exam trap The SA node receptor is β1. A β2 agonist given for preterm labour relaxes the uterus through β2 but causes tachycardia mostly by reflex (vasodilation) and spill-over onto β1.

Organ responses

• During exercise or "fight or flight", sympathetic activity raises heart rate and contractility, dilates bronchi and pupils, constricts skin and splanchnic vessels, raises blood glucose and free fatty acids, and inhibits gut motility; muscle vessels dilate (β2 and local metabolites).
• When the bladder neck fails to close during emission (diabetic autonomic neuropathy, α1 blockers such as tamsulosin, prostate surgery), semen passes back into the bladder: retrograde ejaculation with a dry orgasm and cloudy post-ejaculation urine.

Remember Erection is parasympathetic (nitric oxide); emission and ejaculation are sympathetic (α1).

Autonomic reflexes and tone

• Vagal tone dominates the resting heart: the intrinsic SA node rate is about 100/min, and vagal discharge slows it to 60–80/min. A transplanted (denervated) heart therefore rests near 100/min and speeds up only slowly in exercise, relying on circulating catecholamines; patients may not feel angina because sensory nerves are cut.
• Carotid sinus massage stretches baroreceptors; impulses in IX reach the nucleus tractus solitarius, which increases vagal output and inhibits sympathetic output, so heart rate and blood pressure fall. It is used to terminate supraventricular tachycardia.
• Oculocardiac reflex: traction on extraocular muscles (classically medial rectus in squint surgery) or pressure on the globe causes bradycardia. Afferent: ophthalmic division of the trigeminal nerve; efferent: vagus. Treat by stopping traction and giving atropine.
• Peritoneal stretch (CO₂ insufflation at laparoscopy), cervical dilatation and visceral traction cause similar vagal bradycardia.
• Vasovagal syncope: sudden withdrawal of sympathetic tone plus vagal bradycardia.

Spinal cord injury: neurogenic shock and autonomic dysreflexia

• Neurogenic shock follows cord injury above about T6: sympathetic outflow is cut, so vessels dilate and unopposed vagal tone slows the heart. The picture is hypotension with bradycardia and warm, dry, pink skin, unlike hypovolaemic shock (tachycardia, cold clammy skin).
• Autonomic dysreflexia appears weeks to months after a lesion at or above T6. A stimulus below the lesion (full bladder, catheterisation, faecal impaction) triggers an unchecked sympathetic reflex below the lesion: massive vasoconstriction and severe hypertension with pale cold skin below. Baroreceptors detect the hypertension and cause vagal bradycardia plus flushing and sweating above the lesion, but descending inhibition cannot pass the injury. Remove the stimulus and sit the patient up; such patients need anaesthesia for bladder or bowel procedures even without sensation.
• Injury to sacral segments S2–S4 abolishes parasympathetic outflow: atonic bladder with retention and overflow, loss of reflex erection, and faecal retention.

Denervation and the pupil

• A denervated structure develops denervation supersensitivity (up-regulated receptors). In Adie's tonic pupil (damaged ciliary ganglion) the pupil is large, reacts poorly to light, constricts slowly to near, and constricts strongly to dilute 0.1% pilocarpine, which has no effect on a normal pupil. A pupil that fails to constrict even to 1% pilocarpine has been pharmacologically dilated.
• Opioids constrict the pupil by disinhibiting the parasympathetic Edinger–Westphal nucleus. Pinpoint pupils: opioids, pontine haemorrhage, organophosphates.
• Frey syndrome after parotidectomy: cut parasympathetic secretomotor fibres (IX, otic ganglion, auriculotemporal nerve) regrow into the sympathetic cholinergic supply of skin sweat glands, so eating causes facial sweating and flushing. The starch-iodine test confirms it.

Horner's syndrome

Interruption of the sympathetic supply to the face and eye anywhere along a three-neuron path: hypothalamus to the T1 lateral horn (first order), T1 to the superior cervical ganglion over the lung apex (second order), then along the internal carotid artery (third order). Cutting one cervical sympathetic chain produces on the same side partial ptosis (Müller's muscle), miosis, apparent enophthalmos, anhidrosis (if the lesion lies before the carotid bifurcation) and facial vasodilation. Causes: Pancoast tumour, carotid dissection, lateral medullary infarct, cervical rib, neck surgery.

Neurotransmitter life cycles

• Acetylcholine: made from choline and acetyl-CoA by choline acetyltransferase; release needs calcium entry; broken down by acetylcholinesterase. Botulinum toxin blocks release; organophosphates block the esterase. Loss of cholinergic neurons of the nucleus basalis of Meynert underlies memory loss in Alzheimer disease; cholinesterase inhibitors (donepezil) partly compensate but may cause bradycardia.
• Noradrenaline: tyrosine to DOPA (tyrosine hydroxylase, rate-limiting), then dopamine, then noradrenaline (dopamine β-hydroxylase, inside vesicles). Its action ends mainly by reuptake (uptake 1), then MAO and COMT; the urinary metabolite is vanillylmandelic acid. Cocaine and tricyclics block reuptake.

Toxic syndromes

• Miosis and excess secretions are the earliest muscarinic signs; respiratory failure from bronchorrhoea and weakness kills.

Central neurotransmitters

Exam trap Neurogenic shock is the only shock with bradycardia and warm skin; do not mistake it for haemorrhage.

How FCPS asks about this

• Transmitter released by preganglionic fibres: acetylcholine on nicotinic receptors, in both divisions.
• Sympathetic effect mediated by acetylcholine on muscarinic receptors: eccrine sweating.
• Unilateral cervical sympathetic chain cut: ptosis, miosis, anhidrosis and facial flushing on the same side.
• Heart rate after cardiac transplant: about 100/min at rest, slow rise with exercise; no vagal tone.
• Cervical cord injury with low BP, low pulse, warm skin: neurogenic shock; late paroxysmal hypertension with a full bladder is autonomic dysreflexia.
• Bradycardia in squint surgery: oculocardiac reflex, trigeminal afferent and vagal efferent.
• Dry orgasm in diabetes: bladder neck fails to close (loss of α1 sympathetic action): retrograde ejaculation.