Two outflows, one transmitter at every ganglion,
and the whole of cardiovascular anaesthesia falls out of it.

The minimum high-yield framework

1. Two neurons in series from central nervous system to effector, with a ganglion between them. This is the defining structural feature — the somatic system has one.
2. Sympathetic = thoracolumbar, T1 to L2/L3. Parasympathetic = craniosacral, cranial nerves III, VII, IX and X and sacral segments S2 to S4.
3. Sympathetic ganglia lie close to the cord — short preganglionic, long postganglionic fibres, and wide divergence, so responses are diffuse.
4. Parasympathetic ganglia lie in or on the target organ — long preganglionic, short postganglionic fibres, and little divergence, so responses are discrete.
5. Every preganglionic fibre is cholinergic, acting on nicotinic receptors — in both divisions, without exception.
6. Postganglionic: parasympathetic is cholinergic on muscarinic receptors; sympathetic is noradrenergic — except sweat glands, which are cholinergic-muscarinic.
7. The adrenal medulla is a modified sympathetic ganglion, innervated directly by preganglionic fibres, releasing about 80% adrenaline into the blood.
8. Preganglionic fibres are myelinated B fibres — which is why they are blocked first and highest in a neuraxial block.

Note that the afferent limb is shared. Visceral afferents from baroreceptors, chemoreceptors and the viscera travel with autonomic nerves but are not themselves divided into sympathetic and parasympathetic; the two-neuron rule applies to the efferent side only. A third division, the enteric nervous system — the myenteric and submucosal plexuses — has its own intrinsic reflex circuitry and can operate when extrinsic innervation is cut, which is why gut motility continues after transplantation.

Preganglionic cell bodies lie in the intermediolateral cell column of the lateral horn, from T1 to L2 or L3. Their axons leave in the ventral root, pass through the white ramus communicans — white because these fibres are myelinated — and reach the sympathetic chain, where they may:

1. synapse in the chain ganglion at that level;
2. travel up or down the chain and synapse at another level — which is how T1 to L2 outflow reaches the head and the lower limb;
3. pass through without synapsing, as a splanchnic nerve, to a prevertebral ganglion (coeliac, superior or inferior mesenteric);
4. pass through to the adrenal medulla, and synapse on chromaffin cells directly.

Postganglionic fibres rejoin the spinal nerve through the grey ramus communicans — grey because they are unmyelinated — and distribute with it to vessels, sweat glands and piloerector muscles, or travel on arteries to the viscera.

The vagus carries about 75% of all parasympathetic fibres, which is why “parasympathetic effect” and “vagal effect” are used almost interchangeably in clinical practice. Note that the vagus supplies the gut only as far as the distal third of the transverse colon; beyond that the supply is sacral. The watershed is the same point at which the midgut becomes the hindgut, and it explains why colonic function is preserved after vagotomy but not after cauda equina injury.

Noradrenaline: synthesis, release, termination

1. Synthesis. Tyrosine → DOPA, by tyrosine hydroxylase — the rate-limiting step. DOPA → dopamine, by DOPA decarboxylase. Dopamine is taken into the vesicle, where dopamine β-hydroxylase converts it to noradrenaline. In the adrenal medulla only, a further cytoplasmic enzyme, phenylethanolamine N-methyltransferase (PNMT), methylates noradrenaline to adrenaline.
2. Release. Depolarisation opens voltage-gated calcium channels; calcium entry triggers exocytosis of vesicular contents — noradrenaline together with ATP and neuropeptide Y as co-transmitters.
3. Termination — reuptake, principally. Uptake 1 returns about 75-80% into the presynaptic neuron. Uptake 2 takes a smaller fraction into extraneuronal tissue. The remainder diffuses away and is metabolised. This is the crucial contrast with acetylcholine, which is destroyed enzymatically in the cleft in milliseconds.
4. Metabolism. Monoamine oxidase acts on noradrenaline recaptured into the neuron; catechol-O-methyltransferase acts extraneuronally, in liver and kidney. The common end product is vanillylmandelic acid, excreted in urine and measured in the investigation of phaeochromocytoma.

Chromaffin cells are modified postganglionic sympathetic neurons: they derive from the neural crest, are innervated directly by preganglionic cholinergic fibres acting on nicotinic receptors, and have no axons. Instead of releasing transmitter at a synapse they secrete into the circulation, converting a neural signal into a hormonal one.

The anatomy explains a clinical detail: ganglion blockade abolishes adrenal medullary secretion, because the synapse involved is nicotinic like any other ganglion, whereas an adrenergic neuron blocker does not.

The baroreceptor reflex, as the worked example

1. Receptor. Stretch-sensitive endings in the carotid sinus and aortic arch — mechanoreceptors, so they respond to wall stretch rather than to pressure as such.
2. Afferent. Carotid sinus via the glossopharyngeal nerve (nerve of Hering); aortic arch via the vagus.
3. Centre. The nucleus tractus solitarius in the medulla, which projects to the nucleus ambiguus and dorsal motor nucleus (vagal outflow) and to the rostral ventrolateral medulla (sympathetic outflow).
4. Efferent and response. A rise in pressure increases baroreceptor firing, which increases vagal outflow and decreases sympathetic outflow: bradycardia, reduced contractility, vasodilatation and venodilatation, so pressure falls. A fall in pressure does the reverse. It is a negative feedback loop with a latency of one or two beats.

The reflex resets over one to two days in sustained hypertension, which is why chronic hypertensives defend a higher pressure and tolerate a fall poorly. It is blunted by volatile and intravenous anaesthetics, by age, by diabetic autonomic neuropathy and by β blockade, which is the physiological reason induction produces a larger fall in blood pressure in exactly those patients.

Previously examinedApril 2019 · October 2021 — the autonomic nervous system, and the physiological consequences of sympathetic blockade during neuraxial anaesthesia. Worked answers in the library

General anaesthesia

Volatile agents and propofol depress central sympathetic outflow and blunt the baroreceptor reflex, so hypotension is not fully compensated. Volatiles are additionally direct vasodilators and negative inotropes. The relative preservation of vagal tone is why a bradycardic response to laryngoscopy or traction is seen in children and in patients on β blockers. Etomidate and ketamine are the conventional exceptions — etomidate for cardiovascular stability, ketamine for its indirect sympathomimetic effect through inhibition of catecholamine reuptake, which is why it depresses the myocardium in a catecholamine-depleted patient.

Autonomic neuropathy

Long-standing diabetes, uraemia, amyloidosis and Parkinson’s disease produce an autonomic neuropathy characterised by resting tachycardia with loss of beat-to-beat heart rate variability, postural hypotension, gastroparesis and impaired thermoregulation. Anaesthetic implications: an exaggerated hypotensive response to induction and to neuraxial block, a blunted response to hypovolaemia, an increased aspiration risk from delayed gastric emptying, and a greater tendency to intraoperative hypothermia.

Autonomic dysreflexia

In a patient with a cord lesion at or above T6, a noxious stimulus below the level — most often bladder or bowel distension — triggers a massive, unmodulated sympathetic discharge from the isolated cord below the lesion, producing severe hypertension. Descending inhibition cannot reach the isolated segments. The baroreceptor reflex is intact above the lesion, so it responds with bradycardia and flushing and sweating above the level of the lesion, with pallor and vasoconstriction below. It is a hypertensive emergency risking intracranial haemorrhage. Treatment is to remove the stimulus, sit the patient up, and use a short-acting vasodilator; prevention is adequate anaesthesia — including for procedures below a level where the patient has no sensation, since the reflex arc does not require sensation.