Autonomic Nervous System
Physiology · CNS · lean revision notes
Autonomic Nervous System
The autonomic nervous system (ANS) is the involuntary, visceral motor division that maintains homeostasis through the antagonistic sympathetic ("fight or flight") and parasympathetic ("rest and digest") arms. For NEET PG, the high-yield zones are anatomical origins, neurotransmitter–receptor pairing, organ-wise receptor effects, the classic pupil eponyms (Horner, Argyll Robertson, Adie), and pharmacological manipulation.
Definition & organisation
The ANS is the efferent (motor) supply to smooth muscle, cardiac muscle and glands. Unlike the somatic system (single myelinated motor neuron, no ganglion, always excitatory, releases acetylcholine acting on nicotinic receptors at the neuromuscular junction), the autonomic pathway is a two-neuron chain: a preganglionic neuron synapses in a peripheral ganglion on a postganglionic neuron that reaches the effector.
Three divisions are recognised:
- Sympathetic — thoracolumbar outflow.
- Parasympathetic — craniosacral outflow.
- Enteric nervous system — intrinsic gut plexuses (Meissner submucosal, Auerbach myenteric); "the second brain", capable of autonomous reflex activity.
High-yield: Somatic motor neurons and ALL autonomic preganglionic fibres are cholinergic acting on nicotinic ganglionic (Nn) receptors. The only difference between the two divisions lies in the postganglionic transmitter.
Sympathetic (thoracolumbar) anatomy
- Preganglionic cell bodies lie in the intermediolateral horn (lateral grey column) of spinal segments T1–L2/L3.
- Fibres exit via the ventral root and white rami communicantes to reach the paravertebral sympathetic chain (22 ganglia) or pass through to prevertebral (collateral) ganglia (coeliac, superior & inferior mesenteric).
- Short preganglionic, long postganglionic fibres.
- Exception 1: the adrenal medulla is a modified sympathetic ganglion — preganglionic cholinergic fibres (splanchnic) synapse directly on chromaffin cells, releasing ~80% adrenaline + 20% noradrenaline into blood (so it is a one-neuron pathway with no postganglionic fibre).
- Exception 2: sweat glands and some skeletal-muscle vasodilator fibres are anatomically sympathetic but use acetylcholine on muscarinic receptors (sympathetic cholinergic).
Parasympathetic (craniosacral) anatomy
- Cranial outflow via cranial nerves III, VII, IX, X and sacral outflow from S2–S4.
- Long preganglionic, short postganglionic fibres (ganglia lie in/near the target organ).
- The vagus (X) supplies thoraco-abdominal viscera down to roughly the splenic flexure (two-thirds of transverse colon); the distal colon and pelvic viscera receive the sacral outflow (pelvic splanchnic nerves, nervi erigentes).
- Cranial parasympathetic ganglia (must memorise): ciliary (CN III → sphincter pupillae, ciliary muscle), pterygopalatine (CN VII → lacrimal/nasal glands), submandibular (CN VII → submandibular & sublingual glands), otic (CN IX → parotid).
| Feature | Sympathetic | Parasympathetic |
|---|---|---|
| Outflow | Thoracolumbar (T1–L2/3) | Craniosacral (III, VII, IX, X; S2–4) |
| Preganglionic fibre | Short | Long |
| Postganglionic fibre | Long | Short |
| Ganglia location | Para-/prevertebral (near cord) | In/near target organ |
| Postganglionic transmitter | Noradrenaline (mostly) | Acetylcholine |
| Divergence | High (mass discharge) | Low (discrete) |
| Dominant tone | Heart, arterioles, sweat glands | SA node (at rest), GI, bladder, eye |
Neurotransmitters & receptors
Acetylcholine (ACh) is released at: all preganglionic terminals (both divisions), all parasympathetic postganglionic terminals, sympathetic postganglionic to sweat glands, and the somatic NMJ. ACh is synthesised from choline + acetyl-CoA by choline acetyltransferase and degraded by acetylcholinesterase.
Noradrenaline (NA) is the main sympathetic postganglionic transmitter. Synthesis: Tyrosine → DOPA (via tyrosine hydroxylase, the rate-limiting step) → dopamine → noradrenaline (via dopamine β-hydroxylase) → (in adrenal medulla only) adrenaline via PNMT. Action is terminated chiefly by reuptake-1 (NET) into the nerve terminal, then metabolised by MAO (mitochondrial) and COMT (extraneuronal). Urinary metabolite = VMA (raised in phaeochromocytoma).
Cholinergic receptors
- Nicotinic (ionotropic, ligand-gated cation channels): Nn (Nq) on autonomic ganglia & adrenal medulla; Nm on skeletal muscle.
- Muscarinic (GPCR):
- M1 — neural (CNS, gastric parietal cells, ganglia) → Gq.
- M2 — cardiac (SA/AV node) → Gi → bradycardia, decreased conduction.
- M3 — smooth muscle & glands (bronchoconstriction, GI/bladder contraction, secretion, pupillary sphincter → miosis, vascular endothelial NO release → vasodilatation) → Gq.
Adrenergic receptors
| Receptor | G-protein | Second messenger | Key actions |
|---|---|---|---|
| α1 | Gq | ↑ IP3/DAG, ↑ Ca²⁺ | Vasoconstriction, mydriasis (radial muscle), bladder/sphincter contraction, ↑ peripheral resistance |
| α2 | Gi | ↓ cAMP | Presynaptic autoinhibition of NA release; central sympatholysis; ↓ insulin; platelet aggregation |
| β1 | Gs | ↑ cAMP | ↑ Heart rate, contractility, AV conduction; renin release |
| β2 | Gs | ↑ cAMP | Bronchodilation, vasodilation (skeletal muscle), uterine relaxation, glycogenolysis, tremor |
| β3 | Gs | ↑ cAMP | Lipolysis; detrusor relaxation (mirabegron target) |
| D1 | Gs | ↑ cAMP | Renal/splanchnic vasodilation |
High-yield: Order of receptor potency — α: NA > Adr >> Isoprenaline; β: Isoprenaline > Adr > NA. Adrenaline acts on all; noradrenaline has negligible β2 action; isoprenaline is a pure β agonist.
High-yield: Adrenaline reversal (Dale's phenomenon) — after an α-blocker (e.g., prazosin/phentolamine), adrenaline's pressor (α1) effect is abolished and its unmasked β2 vasodilatation drops blood pressure further. Noradrenaline is NOT reversed (no significant β2 action).
Organ-wise effects (the perennial table)
| Organ | Sympathetic (receptor) | Parasympathetic (M3/M2) |
|---|---|---|
| Eye – pupil | Mydriasis (α1, dilator) | Miosis (M3, sphincter) |
| Eye – ciliary | Slight relaxation (β2) → far vision | Contraction (M3) → near vision (accommodation) |
| Heart – rate | ↑ (β1) | ↓ (M2) |
| Bronchi | Dilate (β2) | Constrict + secretion (M3) |
| GI motility | ↓ (α2, β2) | ↑ (M3) |
| GI sphincters | Contract (α1) | Relax |
| Bladder detrusor | Relax (β3) | Contract (M3) → voiding |
| Bladder trigone/sphincter | Contract (α1) → continence | Relax |
| Blood vessels (skin/splanchnic) | Constrict (α1) | – |
| Skeletal muscle vessels | Dilate (β2) | – |
| Sweat glands | ↑ secretion (M3, cholinergic) | – |
| Liver | Glycogenolysis (α1, β2) | – |
| Kidney | Renin (β1) | – |
| Male sexual function | Ejaculation (α1) | Erection (M3, NO) |
High-yield mnemonic for erection/ejaculation: "Point and Shoot" — Parasympathetic = Point (erection), Sympathetic = Shoot (ejaculation).
Autonomic reflexes
- Baroreceptor reflex: carotid sinus (CN IX) & aortic arch (CN X) sense ↑ BP → afferents to NTS → ↑ vagal (bradycardia) + ↓ sympathetic (vasodilation). The basis of carotid sinus massage for SVT.
- Bainbridge reflex: ↑ right atrial stretch/venous return → reflex tachycardia.
- Bezold–Jarisch reflex: ventricular chemo/mechanoreceptors → bradycardia, hypotension, apnoea (relevant in inferior MI, spinal anaesthesia).
- Cushing reflex: ↑ intracranial pressure → hypertension + bradycardia + irregular respiration (Cushing's triad).
- Oculocardiac reflex: pressure on globe → bradycardia (V1 afferent, vagal efferent) — strabismus surgery.
Clinical syndromes (eponyms — exam favourites)
Horner syndrome
Interruption of the oculosympathetic pathway (3-neuron arc: hypothalamus → ciliospinal centre of Budge C8–T2 → superior cervical ganglion → along internal carotid). Triad: PAM — Ptosis (partial, Müller's muscle), Anhidrosis, Miosis; plus apparent enophthalmos.
- Pupil is small but reacts to light and accommodation (dilator failure only).
- Cocaine test confirms (no dilation as NA reuptake-block has no NA to act on); apraclonidine causes reversal of anisocoria. Hydroxyamphetamine localises pre- vs postganglionic.
- Causes: Pancoast tumour, carotid dissection, lateral medullary (Wallenberg) syndrome, neck trauma.
Argyll Robertson pupil ("Prostitute's pupil")
Bilateral small, irregular pupils that accommodate but do not react to light (light-near dissociation), classically due to neurosyphilis (also diabetes). Mnemonic: "Accommodates but Reacts not" / "Prostitute's pupil — accommodates but does not react." Lesion in the pretectal region.
Holmes–Adie (tonic) pupil
Large pupil with slow, tonic response to accommodation and poor light reaction; due to ciliary ganglion damage; denervation supersensitivity → constricts to dilute (0.1%) pilocarpine. With absent deep tendon reflexes = Adie syndrome.
| Pupil | Light reaction | Near reaction | Size | Classic cause |
|---|---|---|---|---|
| Argyll Robertson | Absent | Preserved | Small, irregular | Neurosyphilis |
| Holmes–Adie | Sluggish/absent | Slow, tonic | Large | Ciliary ganglion lesion |
| Horner | Preserved | Preserved | Small | Sympathetic interruption |
| Marcus Gunn (RAPD) | Paradoxical dilation on swinging torch | – | – | Optic nerve disease |
Diagnosis & investigation of choice
- Autonomic function tests: Heart-rate variability with deep breathing (E:I ratio), Valsalva ratio, 30:15 ratio on standing (parasympathetic); BP response to standing/sustained handgrip, cold pressor test (sympathetic).
- Tilt-table test — investigation of choice for neurally mediated (vasovagal) syncope and orthostatic hypotension.
- Orthostatic hypotension defined as fall in systolic ≥20 mmHg or diastolic ≥10 mmHg within 3 minutes of standing.
- Phaeochromocytoma: plasma-free metanephrines (most sensitive); urinary metanephrines/VMA; localise with CT/MRI and MIBG scan.
- Pharmacological pupil testing as above for Horner/Adie.
Management / drugs of choice
High-yield drug pearls:
- Atropine (muscarinic antagonist) — drug of choice for symptomatic bradycardia and for organophosphate poisoning (block muscarinic effects; pralidoxime reactivates cholinesterase if given early, before "ageing").
- Adrenaline — drug of choice for anaphylaxis (IM 0.5 mg of 1:1000) and cardiac arrest.
- Pilocarpine (muscarinic agonist) — used in glaucoma and xerostomia.
- Pralidoxime is ineffective in carbamate poisoning and once the enzyme has "aged".
Cholinergic crisis vs organophosphate (anticholinesterase) toxicity
Muscarinic excess mnemonic DUMBBELS: Diarrhoea, Urination, Miosis, Bronchorrhoea/Bronchospasm, Bradycardia, Emesis, Lacrimation, Salivation. (Alternative: SLUDGE.) Treat with atropine titrated to drying of secretions.
Anticholinergic ("atropine") toxidrome
"Hot as a hare, dry as a bone, red as a beet, mad as a hatter, blind as a bat" — hyperthermia, dry skin/mouth, flushing, delirium, mydriasis/cycloplegia, urinary retention. Antidote: physostigmine (crosses BBB).
Key autonomic drug classes
- Sympathomimetics: phenylephrine (α1), clonidine/dexmedetomidine (α2 central — sympatholytic, sedation, antihypertensive), dobutamine (β1), salbutamol (β2), mirabegron (β3 — overactive bladder).
- Sympatholytics: prazosin (α1 — BPH/HTN), tamsulosin (α1A — BPH), phentolamine (non-selective α, also for adrenaline extravasation), propranolol (non-selective β), metoprolol (β1), carvedilol/labetalol (α+β).
- Phaeochromocytoma: α-blockade first (phenoxybenzamine) THEN β-blockade — never β alone (unopposed α → hypertensive crisis).
Complications
- Autonomic dysreflexia in spinal cord injury above T6 — noxious stimulus below the lesion (blocked catheter, faecal impaction) → massive sympathetic surge: severe hypertension, pounding headache, flushing/sweating above lesion, reflex bradycardia. Emergency: sit patient up, remove trigger, antihypertensives.
- Diabetic autonomic neuropathy — resting tachycardia, gastroparesis, postural hypotension, erectile dysfunction, silent ischaemia, sudden death.
- Multiple system atrophy (Shy–Drager) — autonomic failure + parkinsonism/cerebellar signs.
- Pure autonomic failure and familial dysautonomia (Riley–Day).
- Hypertensive crisis from unopposed α stimulation (phaeo, MAOI–tyramine "cheese reaction").
Key differentials
- Causes of miosis: Horner, Argyll Robertson, opioid/organophosphate toxicity, pontine haemorrhage, pilocarpine.
- Causes of mydriasis: CN III palsy, Adie pupil, atropine/anticholinergic, cocaine/amphetamine, brain herniation (blown pupil).
- Ptosis differential: Horner (partial, + miosis) vs CN III palsy (complete, + mydriasis, "down-and-out" eye) vs myasthenia gravis (fatigable, normal pupil).
- Bradycardia–hypertension differential: Cushing reflex vs autonomic dysreflexia vs Bezold–Jarisch.
Recently asked / exam angle
- Distinguish the partial ptosis + miosis of Horner from the complete ptosis + mydriasis of third-nerve palsy — repeatedly tested image-based question.
- Light-near dissociation → Argyll Robertson (small, neurosyphilis) vs Adie (large, tonic).
- Receptor for sweating = muscarinic despite sympathetic innervation (sympathetic cholinergic) — classic single-best-answer trap.
- Tyrosine hydroxylase as the rate-limiting enzyme of catecholamine synthesis.
- Sequence of blockade in phaeochromocytoma (α before β) and adrenaline reversal mechanism.
- Atropine + pralidoxime in organophosphate poisoning; pralidoxime useless after enzyme ageing and in carbamates.
- M2 = Gi cardiac, M3 = Gq smooth muscle/gland; α2 presynaptic autoinhibition.
- Tilt-table as test of choice for vasovagal syncope; orthostatic hypotension numeric cut-offs (20/10 mmHg).
- Vagus supplies gut up to splenic flexure; distal colon by sacral (S2–4) outflow.
Rapid revision
- Sympathetic = thoracolumbar (T1–L2/3), short pre/long post fibres; parasympathetic = craniosacral (III, VII, IX, X; S2–4), long pre/short post.
- ALL preganglionic + all parasympathetic postganglionic + sweat glands + somatic NMJ are cholinergic; sympathetic postganglionic (except sweat) are noradrenergic.
- Ganglionic and NMJ receptors are nicotinic; effector parasympathetic receptors are muscarinic.
- Adrenal medulla = modified sympathetic ganglion → 80% adrenaline into blood (no postganglionic neuron).
- α1 = Gq vasoconstriction/mydriasis; α2 = Gi presynaptic autoinhibition; β1 = Gs heart + renin; β2 = Gs bronchodilation/vasodilation; M2 = Gi heart; M3 = Gq smooth muscle/glands.
- Tyrosine hydroxylase = rate-limiting step; NA terminated by reuptake (NET); metabolites MAO/COMT; urinary VMA in phaeo.
- Horner = ptosis + miosis + anhidrosis (PAM), pupil reacts to light; cocaine/apraclonidine tests.
- Argyll Robertson = small irregular pupils, accommodate but don't react (neurosyphilis); Adie = large tonic pupil + areflexia, supersensitive to dilute pilocarpine.
- Atropine for symptomatic bradycardia & organophosphate (+ pralidoxime before ageing; useless in carbamates).
- Phaeochromocytoma: α-block (phenoxybenzamine) BEFORE β-block; plasma metanephrines + MIBG scan.
- Adrenaline reversal occurs with α-blockers (β2 unmasked); noradrenaline is not reversed.
- Autonomic dysreflexia (SCI above T6): hypertension + bradycardia + headache from a noxious stimulus below the lesion — sit up, remove trigger.