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Chapter 9: The Autonomic Nervous System (ANS)

Based on Stuart Fox's "Human Physiology" - fully cross-referenced with Ganong's Review of Medical Physiology (26th ed.) and Guyton & Hall

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Note: Stuart Fox's "Human Physiology" is not in the digital library, but Chapter 9 of Fox covers the same standard ANS content found in all major MBBS physiology textbooks. Everything below is drawn from Ganong (Chapter 13) and Guyton & Hall, which cover this topic identically - Ganong's Review of Medical Physiology, Ch. 13

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1. OVERVIEW OF THE ANS

1. Sympathetic nervous system (thoracolumbar outflow)
2. Parasympathetic nervous system (craniosacral outflow)
3. Enteric nervous system (intrinsic gut nervous system)

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2. KEY STRUCTURAL DIFFERENCE: TWO-NEURON CHAIN

• Preganglionic neurons: Cell bodies in the CNS (spinal cord IML column or cranial nerve nuclei); axons are small myelinated B fibers
• Postganglionic neurons: Cell bodies in peripheral ganglia; axons are unmyelinated C fibers terminating on effector organs

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3. THE SYMPATHETIC DIVISION

Origin (Thoracolumbar Outflow)

• Preganglionic cell bodies are in the intermediolateral (IML) column of the spinal cord from T1 to L2-L3
• Hence called the thoracolumbar division

Pathway

1. Preganglionic axons exit via ventral roots with alpha- and gamma-motor axons
2. They leave via white rami communicantes (myelinated - hence "white")
3. Enter the paravertebral sympathetic chain (paired chain ganglia on each side of the vertebral column)
4. Here they may:
   • Synapse at the same level and postganglionic fiber exits via gray rami communicantes (unmyelinated) to join spinal nerves
   • Ascend or descend in the chain to synapse at a different level
   • Pass through without synapsing to reach prevertebral (collateral) ganglia - celiac, superior mesenteric, inferior mesenteric ganglia

The Sympathetic Chain (Paravertebral Ganglia)

• 22-23 ganglia on each side: 3 cervical, 12 thoracic, 4-5 lumbar, 4-5 sacral
• The superior cervical ganglion is the largest - innervates the head
• Gray rami communicantes (postganglionic fibers) exist at ALL spinal levels; white rami only at T1-L2

Special Case: Adrenal Medulla

• The adrenal medulla is a modified sympathetic ganglion
• Preganglionic fibers go directly to chromaffin cells (which are modified postganglionic neurons)
• Chromaffin cells release epinephrine (80%) and norepinephrine (20%) directly into the bloodstream
• This is why the adrenal medulla acts as an "endocrine arm" of the sympathetic system

Sympathetic Preganglionic to Postganglionic Ratio

• 1 preganglionic neuron may synapse on 20-30 postganglionic neurons
• This divergence produces the mass discharge / diffuse activation seen during sympathetic storms

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4. THE PARASYMPATHETIC DIVISION

Origin (Craniosacral Outflow)

• Preganglionic neurons arise from cranial nerve nuclei and the sacral spinal cord (S2-S4)
• Hence called the craniosacral division

Cranial Component - Four Cranial Nerves:

Sacral Component:

• Preganglionic fibers from S2, S3, S4 form the pelvic nerve (pelvic splanchnic nerves)
• Supply: distal colon, rectum, urinary bladder, sex organs

Key anatomical feature:

• Parasympathetic ganglia are located in or very near the target organ (terminal ganglia)
• Therefore, postganglionic fibers are very short (in contrast to sympathetic where they are long)
• The preganglionic-to-postganglionic ratio is much lower (~1:3) - leading to more discrete, localized responses compared to the diffuse sympathetic response

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5. NEUROTRANSMITTERS AND RECEPTORS

5.1 Cholinergic vs. Adrenergic Neurons

1. All preganglionic sympathetic neurons
2. All preganglionic parasympathetic neurons
3. All postganglionic parasympathetic neurons
4. Some postganglionic sympathetic neurons - specifically:
   • Fibers to sweat glands (sudomotor)
   • Fibers causing vasodilation in some skeletal muscle blood vessels

• Most postganglionic sympathetic neurons (the majority)

5.2 Cholinergic Receptors (respond to ACh)

Nicotinic Receptors (N)

• Found at: all autonomic ganglia (both sympathetic and parasympathetic), the neuromuscular junction, and the adrenal medulla
• Type: Ionotropic (ligand-gated ion channels) - fast response
• Subtypes: N1 (ganglionic, Nn) and N2 (muscle, Nm)
• Activated by: nicotine
• Blocked by: hexamethonium (N1/ganglionic), tubocurarine (N2/muscle)

Muscarinic Receptors (M)

• Found at: all postganglionic parasympathetic targets, sweat glands (sympathetic cholinergic)
• Type: Metabotropic (G-protein coupled) - slower, sustained response
• Five subtypes: M1 through M5

• Activated by: muscarine, ACh
• Blocked by: atropine (all M subtypes)

5.3 Adrenergic Receptors (respond to catecholamines: NE and Epinephrine)

Alpha (α) Receptors

Beta (β) Receptors

• Epinephrine acts on α1, α2, β1, β2 (all types)
• Norepinephrine acts mainly on α1, α2, β1 (weak β2 activity)
• Isoproterenol (synthetic) acts only on β1, β2 (pure β agonist)

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6. SYNTHESIS, STORAGE, AND INACTIVATION OF NEUROTRANSMITTERS

6.1 Acetylcholine Synthesis and Fate

Choline + Acetyl-CoA → ACh (enzyme: Choline acetyltransferase / ChAT)

ACh → Choline + Acetate (enzyme: Acetylcholinesterase / AChE, found in synapse)

• Choline is taken back up into the neuron (70-80% recycled)
• Hemicholinium blocks choline uptake, depleting ACh stores

6.2 Catecholamine Synthesis and Fate

Tyrosine → DOPA → Dopamine → Norepinephrine → Epinephrine

1. Reuptake (Uptake-1): NE re-enters presynaptic neuron via NET (norepinephrine transporter) - the main mechanism. Blocked by cocaine, tricyclic antidepressants
2. Enzymatic degradation:
   • MAO (monoamine oxidase) - intracellular, in mitochondria; metabolizes NE to VMA
   • COMT (catechol-O-methyltransferase) - extracellular/synaptic cleft

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7. EFFECTS OF SYMPATHETIC AND PARASYMPATHETIC STIMULATION ON ORGANS

Memory trick: "SLUDD" = Parasympathetic effects: Salivation, Lacrimation, Urination, Defecation, Digestion. Sympathetic = "Fight or Flight" - dilate pupils, dilate airways, elevate HR/BP, divert blood to muscles.

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8. OVERALL FUNCTIONAL ROLES

Sympathetic - "Fight or Flight" (Catabolic)

• Dilates pupils - more light
• Accelerates heart rate and increases blood pressure - better organ/muscle perfusion
• Dilates bronchioles - more O2 in
• Constricts skin blood vessels - limits bleeding from wounds
• Raises blood glucose and free fatty acids - more energy available
• Diverts blood away from gut to muscles
• Discharges as a unit (mass discharge) - the entire sympathetic system fires together

Parasympathetic - "Rest and Digest" (Anabolic)

• Promotes digestion and absorption - increases intestinal motility, increases gastric secretion
• Slows heart rate (conservation)
• Constricts pupils
• Empties bladder and bowel
• Promotes sexual arousal (erection)
• Acts in a discrete, localized manner (not mass discharge)

Dual Innervation - Antagonistic vs. Cooperative:

• Antagonistic: Heart rate (symp ↑, para ↓), bronchi (symp dilates, para constricts), bladder (symp fills, para empties)
• Complementary: Salivary glands (both stimulate saliva but of different types - para = watery, symp = viscous)
• Synergistic: Sexual function (para = erection, symp = ejaculation - both needed for complete sexual response); pupil size (both exert opposite but cooperative effects)
• Only sympathetic innervation: Blood vessels (most), sweat glands, piloerector muscles, adrenal medulla
• Only parasympathetic innervation: Lacrimal glands, ciliary muscle, nasopharyngeal glands

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9. THE ENTERIC NERVOUS SYSTEM (ENS)

• A vast network of neurons embedded in the wall of the GI tract (from esophagus to anus)
• Two major plexuses:
  1. Myenteric plexus (Auerbach's plexus) - between longitudinal and circular muscle layers; controls GI motility
  2. Submucosal plexus (Meissner's plexus) - in the submucosa; controls secretion and absorption
• Can function independently of the CNS (reflexes can occur even after complete vagal/sympathetic denervation)
• Contains ~100 million neurons (more than the spinal cord)
• Uses neurotransmitters: ACh, substance P, serotonin (5-HT), VIP, nitric oxide, enkephalins

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10. CENTRAL CONTROL OF THE ANS

1. Hypothalamus - the primary integrating center for ANS activity
   • Posterior/lateral hypothalamus: sympathetic activation
   • Anterior/medial hypothalamus: parasympathetic activation
   • Controls body temperature, fluid balance, appetite, circadian rhythms
2. Brainstem centers:
   • Nucleus tractus solitarius (NTS) - receives visceral sensory input (baroreceptors, chemoreceptors)
   • Rostral ventrolateral medulla (RVLM) - controls sympathetic tone to cardiovascular system
   • Dorsal vagal nucleus and nucleus ambiguus - control parasympathetic outflow to heart and gut
3. Limbic system and cerebral cortex - emotional responses activate the ANS (blushing, sweating from anxiety, emotional tachycardia)
4. Spinal cord - autonomic reflexes can occur at spinal level (e.g., spinal cord injury can still allow some autonomic reflexes)

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11. AUTONOMIC TONE

• Sympathetic tone maintains blood pressure (tonic vasoconstriction)
• Parasympathetic tone maintains resting heart rate lower than the intrinsic SA node rate (~100 bpm)
  • Intrinsic SA node rate without any innervation = ~100 bpm
  • Normal resting HR = ~70 bpm (due to dominant parasympathetic tone)
  • After complete autonomic block: HR rises to ~100 bpm
  • After only vagal block (atropine): HR rises to ~150 bpm (sympathetic unopposed)

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12. AUTONOMIC DYSREFLEXIA AND CLINICAL DISORDERS

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13. KEY PHARMACOLOGY SUMMARY

Drugs Acting on the ANS

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SUMMARY TABLE: SYMPATHETIC vs. PARASYMPATHETIC

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• Organization and divisions
• Anatomy and neuronal pathways
• Neurotransmitters and receptors (nicotinic, muscarinic, adrenergic)
• Synthesis and inactivation of ACh and NE
• Organ-by-organ effects
• Central regulation
• Autonomic tone
• Enteric nervous system
• Clinical disorders and pharmacology

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Excitatory vs. Inhibitory ANS Receptors

Important principle: Excitatory/inhibitory refers to the effect on the target tissue, not the receptor itself. The same receptor type (e.g., M3) can cause contraction in one smooth muscle and relaxation in another.

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NICOTINIC RECEPTORS - Always EXCITATORY

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MUSCARINIC RECEPTORS - Mixed (depends on subtype and tissue)

Key point for M2: It is the classic inhibitory muscarinic receptor - it slows the heart. This is why vagal stimulation (parasympathetic, M2) causes bradycardia.

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ADRENERGIC RECEPTORS - Mixed (highly tissue-dependent)

Alpha Receptors

Beta Receptors

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Quick Reference Summary

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The Single Most Tested Concept