autonomic nervous system

**ANATOMY / ORGANIZATION** - Two-neuron efferent chain: preganglionic neuron (CNS, myelinated B fibers) → autonomic ganglion → postganglionic neuron (unmyelinated C fibers) → effector organ. - **Sympathetic (thoracolumbar, T1–L2):** Short preganglionic, long postganglionic fibers. Ganglia are paravertebral (sympathetic chain) or prevertebral (celiac, superior/inferior mesenteric). Lateral horn of spinal cord (intermediolateral cell column) is the origin. - **Parasympathetic (craniosacral):** CN III, VII, IX, X and S2–S4 (pelvic splanchnic nerves). Long preganglionic, short postganglionic fibers; ganglia lie near or within the target organ. The vagus nerve (CN X) supplies most thoracic and abdominal viscera up to the splenic flexure; S2–S4 supplies the distal colon, bladder, and genitals ("S2, 3, 4 keep the penis off the floor"; erection = parasympathetic, ejaculation = sympathetic: "point and shoot"). - **Enteric nervous system:** Myenteric (Auerbach) plexus controls motility; submucosal (Meissner) plexus controls secretion and absorption. It is modulated by the ANS but can function independently.

**NEUROTRANSMITTERS AND RECEPTORS** - ACh is released by all preganglionic neurons (sympathetic and parasympathetic) onto nicotinic (Nn) receptors at the ganglia. - Parasympathetic postganglionic: ACh → muscarinic receptors (M1–M5). - M1: CNS, enteric nervous system (Gq) - M2: heart, decreases HR and contractility (Gi) - M3: smooth muscle contraction, glands, pupillary constriction (Gq) - Sympathetic postganglionic: norepinephrine (NE) → adrenergic receptors. **Exceptions:** sweat glands (muscarinic, ACh) and renal vascular smooth muscle (dopamine D1). - Adrenal medulla: modified sympathetic ganglion. Preganglionic fibers release ACh (nicotinic) onto chromaffin cells, which release ~80% epinephrine and ~20% NE into the blood. - Adrenergic receptors: - α1 (Gq): vasoconstriction, mydriasis, ↑ sphincter tone (bladder, GI) - α2 (Gi): ↓ NE release (presynaptic), ↓ insulin, ↓ aqueous humor - β1 (Gs): ↑ HR, contractility, renin release (JG cells) - β2 (Gs): bronchodilation, vasodilation of skeletal muscle, uterine relaxation, glycogenolysis, lipolysis - β3 (Gs): lipolysis, bladder detrusor relaxation - D1 (Gs): renal and mesenteric vasodilation - Mnemonic for G-protein signaling: "q-i-s-q-i-s-s-s" for α1, α2, β1, β2, M1, M2, M3, D1/D2 (α1=q, α2=i, β=s; M1, 3, α1 = q; M2, α2, D2 = i; D1, β1, β2, β3, H2, V2 = s).

**CENTRAL CONTROL AND REFLEXES** - Hypothalamus (integrates), brainstem nuclei (nucleus tractus solitarius receives visceral afferents; dorsal motor nucleus of vagus; nucleus ambiguus; Edinger-Westphal nucleus), and limbic system. - **Baroreceptor reflex:** Carotid sinus (CN IX) and aortic arch (CN X) → NTS. ↑ BP → ↑ parasympathetic and ↓ sympathetic outflow → ↓ HR and BP. Carotid massage activates this reflex, which is used to terminate SVT. - **Pupillary light reflex:** Afferent CN II; efferent parasympathetic CN III (Edinger-Westphal) → ciliary ganglion → sphincter pupillae. - **Micturition:** Parasympathetic (S2–S4) contracts the detrusor and relaxes the internal sphincter. Sympathetic (hypogastric nerve) relaxes the detrusor (β3) and contracts the internal sphincter (α1) for storage. Somatic (pudendal nerve) controls the external sphincter.

**CLINICAL CORRELATES** - **Horner syndrome:** Disrupted sympathetic supply to the head and neck. Triad: ptosis, miosis, anhidrosis (± enophthalmos). Causes: Pancoast tumor, carotid dissection, lateral medullary (Wallenberg) syndrome. - **Autonomic dysreflexia:** Spinal cord lesion at or above T6 → noxious stimulus (bladder distension, fecal impaction) below the lesion → uncontrolled sympathetic surge → severe hypertension, headache, flushing above the lesion, with reflex bradycardia. Treat by removing the trigger (e.g., catheterize) and sitting the patient upright. - **Pheochromocytoma:** Catecholamine-secreting chromaffin tumor → episodic hypertension, headache, sweating, palpitations. Give an α-blocker (phenoxybenzamine) before a β-blocker to avoid unopposed α stimulation. - **Diabetic autonomic neuropathy:** Orthostatic hypotension, gastroparesis, erectile dysfunction, neurogenic bladder, resting tachycardia. - **Neurogenic orthostatic hypotension:** Parkinson disease, multiple system atrophy (Shy-Drager), pure autonomic failure. Treat with fludrocortisone, midodrine (α1 agonist), droxidopa. - **Hirschsprung disease:** Absence of enteric ganglion cells (Auerbach and Meissner plexuses) due to failure of neural crest migration (RET mutation) → functional obstruction. - **Achalasia:** Loss of inhibitory myenteric neurons (NO/VIP) → failure of LES relaxation. - **Guillain-Barré syndrome:** Can cause autonomic instability (arrhythmias, labile BP). - **Botulism:** Blocks ACh release → anticholinergic-like picture (dilated pupils, dry mouth, constipation, urinary retention) with descending paralysis.

**PHARMACOLOGY HIGH-YIELD** - **Cholinomimetics:** Direct agonists (bethanechol: urinary retention/ileus; carbachol, pilocarpine: glaucoma, Sjögren). Indirect (AChE inhibitors): neostigmine, pyridostigmine (myasthenia gravis), physostigmine (anticholinergic toxicity), donepezil (Alzheimer disease), edrophonium. - **Organophosphate poisoning:** Irreversible AChE inhibition → DUMBBELSS (diarrhea, urination, miosis, bronchospasm, bradycardia, emesis, lacrimation, salivation, sweating) plus nicotinic effects (fasciculations, weakness). Treat with atropine (muscarinic) and pralidoxime (reactivates AChE if given early). - **Anticholinergics:** Atropine (bradycardia, organophosphate toxicity), ipratropium/tiotropium (COPD), oxybutynin (overactive bladder), scopolamine (motion sickness), benztropine (Parkinson disease). Toxicity: "hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter." - **Sympathomimetics:** Epinephrine (anaphylaxis), norepinephrine (septic shock), dopamine (low dose D1, medium β1, high α1), dobutamine (β1 > β2; cardiogenic shock), phenylephrine (α1; nasal decongestant, mydriasis), isoproterenol (β1 = β2), albuterol (β2). - **Sympatholytics:** Clonidine and α-methyldopa (central α2 agonists; methyldopa is used in pregnancy), prazosin and other α1 blockers (BPH, hypertension, PTSD nightmares), β-blockers (cardioselective: metoprolol, atenolol, esmolol; nonselective: propranolol, nadolol; carvedilol and labetalol also block α1). - **Ganglionic blockers:** Hexamethonium (nicotinic Nn antagonist). Effects depend on the dominant tone of each organ (parasympathetic in the heart, sympathetic in vasculature). - **Neuromuscular junction (somatic, not ANS):** Nicotinic Nm receptors, so don't confuse with Nn at autonomic ganglia.

**ORGAN EFFECTS (SYMPATHETIC vs PARASYMPATHETIC)** - Eye: Sympathetic → mydriasis (α1; radial dilator muscle); parasympathetic → miosis (M3; sphincter pupillae) and accommodation (ciliary muscle contraction). - Heart: Sympathetic ↑ HR, contractility, conduction velocity (β1); parasympathetic ↓ HR and AV conduction (M2). The SA node is under dominant vagal tone at rest. - Lungs: Sympathetic → bronchodilation (β2); parasympathetic → bronchoconstriction and ↑ secretions (M3). - GI: Sympathetic ↓ motility and constricts sphincters; parasympathetic ↑ motility, secretion, and relaxes sphincters. - Bladder: see micturition above. - Liver/metabolism: Sympathetic → glycogenolysis and gluconeogenesis. - Skin: Sympathetic → piloerection (α1), sweating (muscarinic). - Salivary glands: Sympathetic → thick, viscous saliva (β); parasympathetic → watery, abundant saliva (M3).

**TESTING TIPS** - Know the exceptions: sweat glands (sympathetic cholinergic), adrenal medulla (preganglionic fiber directly), renal vasculature (dopamine). - Sympathetic effects at rest are mostly regulated by vascular tone; the parasympathetic system dominates at rest in the heart. - Predict drug effects by identifying the receptor and G-protein: Gq → ↑ IP3/DAG/Ca²⁺; Gi → ↓ cAMP; Gs → ↑ cAMP. - Remember that the vagus nerve carries ~75% of all parasympathetic fibers.