Table of contents · 10 sections
In a nutshell. The ANS regulates internal organs automatically. Sympathetic — "fight or flight": thoracolumbar outflow (Th1–L2), short pre- and long postganglionic fibers, neurotransmitter — norepinephrine (α1/α2/β1/β2/β3), except for sweat glands and certain vessels (acetylcholine). Parasympathetic — "rest and digest": craniosacral outflow (III, VII, IX, X + S2–S4), long pre- and short postganglionic fibers, neurotransmitter — acetylcholine (M1–M5). Ganglia — nicotinic N-cholinergic receptors. Adrenal medulla — modified sympathetic ganglion: secretes 80% epinephrine + 20% NE.
1. General Organization
- Two divisions: sympathetic and parasympathetic; the enteric nervous system is considered the third division (autonomous GI control).
- Two-neuron transmission chain: preganglionic (CNS → ganglion) + postganglionic (ganglion → effector organ).
- Transmitter in the ganglion — always acetylcholine + nicotinic Nₙ receptors.
- Postganglionic neuron transmitter: sympathetic — NE (exceptions — ACh); parasympathetic — ACh.
2. Sympathetic Division
- Preganglionic nuclei: lateral horns of Th1–L2 (thoracolumbar localization).
- Ganglia: paravertebral (sympathetic trunk), prevertebral (celiac, superior/inferior mesenteric, aortico-renal).
- Features: short pre- and long postganglionic neuron; one preganglionic neuron branches to 10–20 postganglionic neurons.
- Innervation of the adrenal medulla: preganglionic fibers directly, without a ganglion; secretion of epinephrine (80%) and NE (20%) into the bloodstream.
- Exceptions — postganglionic cholinergic fibers: eccrine sweat glands, skeletal muscle blood vessels (β2-vasodilatory), adrenal medulla.
3. Parasympathetic Division
- Preganglionic nuclei: brainstem (nuclei of III, VII, IX, X) + S2–S4 (sacral).
- Ganglia: located near or within target organs → long pre- and short postganglionic fibers.
- CN III — ciliary ganglion (pupil, accommodation).
- CN VII — pterygopalatine and submandibular ganglia (lacrimal, salivary glands).
- CN IX — otic ganglion (parotid salivary gland).
- CN X (vagus) — innervates most internal organs (heart, lungs, GI tract up to the left third of the transverse colon).
- S2–S4 (pelvic nerves) — lower bowel, urinary bladder, genitalia.
4. Receptors
Adrenoreceptors
| Type | Localization | Effects |
|---|---|---|
| α1 | Blood vessels (smooth muscle), radial iris muscle, urinary bladder sphincter, prostate | Vasoconstriction, mydriasis, urinary retention |
| α2 | Presynaptic terminals, β-cells, platelets | ↓ NE release, ↓ insulin, platelet aggregation |
| β1 | Heart, kidneys (JGA) | ↑ HR, ↑ contractility, ↑ renin |
| β2 | Bronchi, skeletal muscle (vessels), uterus, liver | Bronchodilation, vasodilation, tocolysis, glycogenolysis |
| β3 | Adipose tissue, urinary bladder | Lipolysis, detrusor relaxation |
Cholinergic Receptors
| Type | Localization | Effects |
|---|---|---|
| M1 | CNS, stomach | Cognitive functions, ↑ HCl secretion |
| M2 | Heart, presynaptic terminals | ↓ HR, ↓ atrial contractility, AV nodal slowing |
| M3 | Smooth muscle, exocrine glands | Bronchoconstriction, stimulation of secretions, bowel and bladder contraction, miosis |
| M4, M5 | CNS | Modulation of dopaminergic pathways |
| Nₙ (nicotinic) | Autonomic ganglia, adrenal medulla | Depolarization and transmission in the ganglion |
| Nₘ (muscle) | Neuromuscular junction | Skeletal muscle contraction |
5. Functional Effects on Organs
| Organ | Sympathetic | Parasympathetic |
|---|---|---|
| Heart | β1: ↑ HR, contractility, conduction | M2: ↓ HR, ↓ AV conduction |
| Vessels | α1: vasoconstriction; β2: vasodilation (muscles) | Minimal |
| Bronchi | β2: bronchodilation | M3: bronchoconstriction, secretion |
| Pupil | α1: mydriasis | M3: miosis, accommodation |
| Salivary glands | Thick, viscous | Abundant watery |
| GI motility | ↓ tone and secretion | ↑ motility, secretion |
| GI/urinary sphincters | α1: contraction | M3: relaxation |
| Urinary bladder — detrusor | β3: relaxation | M3: contraction |
| Uterus | α1: contraction; β2: relaxation | Variable |
| Genitals | Ejaculation | Erection (NO) |
| Sweat glands | ACh (eccrine); NE (apocrine) | No significant innervation |
| Liver | β2, α1: glycogenolysis, gluconeogenesis | Glycogenesis |
| Pancreas — β-cells | α2 ↓ insulin; β2 ↑ insulin | M3 ↑ insulin |
6. Neurotransmitters and their life cycle
- Norepinephrine: synthesis tyrosine → DOPA → dopamine → NE; stored in vesicles; after release — 80% reuptake via NET, 20% metabolism (MAO, COMT).
- Acetylcholine: synthesis choline + acetyl-CoA (choline acetyltransferase); cleaved in the synapse by acetylcholinesterase.
- Epinephrine: mainly from the adrenal medulla (PNMT converts NE to epinephrine).
7. Pharmacological agents
Sympathomimetics
- Direct α1: phenylephrine (decongestant, pressor).
- Direct α2: clonidine (central), brimonidine (glaucoma).
- Direct β1: dobutamine.
- Direct β2: salbutamol, salmeterol (bronchodilation).
- Direct β3: mirabegron (OAB).
- Non-selective: epinephrine, NE.
- Indirect: amphetamines (NE release), cocaine (NET block).
Sympatholytics
- α1-blockers: doxazosin, tamsulosin (BPH).
- Central α2-agonists: clonidine, methyldopa.
- β-blockers: bisoprolol, metoprolol, carvedilol.
- Ganglionic blockers: hexamethonium (obsolete).
Parasympathomimetics
- Direct: bethanechol, pilocarpine, carbachol.
- Indirect (cholinesterase inhibitors): neostigmine, pyridostigmine, donepezil, rivastigmine (dementia), edrophonium (Tensilon test), physostigmine (anticholinergic poisoning), irreversible — organophosphates (nerve agents, insecticides).
Parasympatholytics (antimuscarinics)
- Atropine, scopolamine, ipratropium (bronchodilation), oxybutynin (bladder), pirenzepine (M1-selective).
8. Clinical syndromes
- Horner's: ptosis + miosis + anhidrosis + enophthalmos — sympathetic lesion at the cervicothoracic level.
- Organophosphate poisoning: SLUDGE/DUMBELS (salivation, lacrimation, urination, defecation, gastrointestinal, emesis; miosis, bradycardia). Treatment: atropine + pralidoxime.
- Anticholinergic poisoning: "hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter". Treatment — physostigmine.
- Autonomic dysreflexia (in spinal cord lesions above Th6): severe hypertension in response to a stimulus below the level of the lesion.
- Orthostatic hypotension — parasympathetic/sympathetic failure (diabetes, Parkinson's disease, MSA).
- Pheochromocytoma — hypercatecholaminemia.
9. ANS tests
- Tilt-table test — orthostatic test.
- Heart rate variability (HRV) — assessment of vagal activity.
- Quantitative sudomotor axon reflex test (QSART) — sudomotor function.
- Valsalva maneuver — baroreflex integration.
- Cold pressor test — sympathetic response.
10. FAQ
Why do β-blockers affect the bronchi differently?
Cardioselective agents (bisoprolol, metoprolol) have lower affinity for β2 — safer in patients with asthma/COPD. Non-selective agents (propranolol) — contraindicated in obstruction.
Why is pralidoxime needed in organophosphate poisoning?
It regenerates acetylcholinesterase before irreversible "aging" occurs. Atropine blocks only muscarinic effects but does not relieve the nicotinic block (convulsions, paralysis).
Why doesn't atropine help in certain asystoles?
Asystole is not associated with increased vagal tone in most cases; atropine has been excluded from the ACLS algorithm for asystole/PEA since 2010.
How is heart rate regulated at rest?
Dominance of vagal tone (M2); intrinsic sinus node rate without ANS influences is ~100 bpm. M2 blockade (atropine) produces tachycardia of ~100; β1 blockade — bradycardia.
What is "mixed" innervation of the salivary glands?
Sympathetic stimulation produces viscous, protein-rich saliva; parasympathetic stimulation produces watery, copious saliva. During stress, the mouth goes "dry" due to sympathetic predominance.
See also: Cholinomimetics · Adrenergics · Horner's syndrome · Pheochromocytoma · Physiology Catalog