# Lecture 19: The Autonomic Nervous System

## Anatomy and Physiology I

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## Learning Objectives

By the end of this lecture, students will be able to:

1. Compare the somatic and autonomic nervous systems in terms of effectors, pathways, and neurotransmitters
2. Describe the two-neuron pathway of the ANS and distinguish preganglionic from postganglionic neurons
3. Compare the sympathetic and parasympathetic divisions in terms of anatomy, neurotransmitters, and receptors
4. Describe the anatomy of the sympathetic division including the sympathetic trunk and splanchnic nerves
5. Describe the anatomy of the parasympathetic division including cranial and sacral outflow
6. Explain the concept of dual innervation and describe the effects of each division on major organ systems
7. Describe the role of the adrenal medulla in the sympathetic response

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## Lecture Content

### I. Overview of the Autonomic Nervous System (ANS)

The autonomic nervous system represents the motor division of the peripheral nervous system responsible for controlling **involuntary** functions, specifically the activity of smooth muscle, cardiac muscle, and glands. Its overarching purpose is to maintain **visceral homeostasis** by regulating heart rate, blood pressure, digestion, respiration, body temperature, urinary function, and reproductive function. Although the ANS operates largely below conscious awareness, some voluntary override is possible, as demonstrated by voluntary breath-holding.

The ANS is organized into two major divisions. The **sympathetic division**, often summarized as "fight-or-flight," mobilizes the body during stress, exercise, and emergencies. The **parasympathetic division**, summarized as "rest-and-digest," promotes energy conservation, digestion, and maintenance activities. A third division is sometimes recognized: the **enteric nervous system**, often called the "brain of the gut." This network of approximately 100 million neurons embedded in the walls of the gastrointestinal tract can function independently but is modulated by the sympathetic and parasympathetic divisions.

### II. Comparison: Somatic vs. Autonomic Motor Pathways

| Feature | Somatic Nervous System | Autonomic Nervous System |
|---|---|---|
| Effectors | Skeletal muscle | Smooth muscle, cardiac muscle, glands |
| Control | Voluntary (conscious) | Involuntary (subconscious) |
| Number of neurons | One (lower motor neuron from CNS to effector) | Two (preganglionic neuron + postganglionic neuron) |
| Neurotransmitter | ACh at the NMJ | ACh and/or NE (varies by division) |
| Effect on effector | Always excitatory (contraction) | Excitatory or inhibitory |
| Myelination | Heavily myelinated (Type A fibers) | Preganglionic: lightly myelinated (Type B); postganglionic: unmyelinated (Type C) |

### III. General ANS Anatomy — The Two-Neuron Chain

The fundamental structural feature distinguishing the autonomic motor pathway from its somatic counterpart is the two-neuron chain. The **preganglionic neuron** has its cell body in the central nervous system, either in the brainstem or the spinal cord, and sends a myelinated axon (a Type B fiber) to an autonomic ganglion. The **autonomic ganglion** is a collection of postganglionic neuron cell bodies located outside the CNS and serves as the synapse point between preganglionic and postganglionic neurons. The **postganglionic neuron** has its cell body in the ganglion and sends an unmyelinated axon (a Type C fiber) to the effector organ.

A critical pharmacological principle is that all preganglionic neurons release **acetylcholine (ACh)** and are therefore classified as cholinergic. The postganglionic neurotransmitter, however, differs between the two divisions. Parasympathetic postganglionic neurons release **ACh** (cholinergic), while sympathetic postganglionic neurons predominantly release **norepinephrine (NE)** (adrenergic), with some notable exceptions.

### IV. The Sympathetic Division (Thoracolumbar Division)

#### Origin

The preganglionic cell bodies of the sympathetic division reside in the **lateral horns** of spinal cord segments **T1 through L2**. Because of this anatomical origin, the sympathetic division is also called the **thoracolumbar division**.

#### Sympathetic Trunk (Paravertebral Ganglia)

The sympathetic trunk consists of two chains of ganglia, one on each side of the vertebral column, extending from the base of the skull to the coccyx. Preganglionic fibers exit the spinal cord via ventral roots, enter the spinal nerve, and then leave through the **white ramus communicans** (named for its myelinated appearance) to enter the sympathetic trunk.

Once a preganglionic fiber enters the trunk, it may follow one of three pathways. First, it may **synapse at the same level**, after which the postganglionic fiber returns to the spinal nerve via the **gray ramus communicans** (unmyelinated) to reach blood vessels, sweat glands, and arrector pili muscles in the body wall and limbs. Second, the fiber may **ascend or descend** within the trunk to synapse at a higher or lower ganglion, allowing sympathetic innervation of the head, neck, and pelvis even though the outflow originates only from T1 through L2. Third, the fiber may **pass through** the trunk without synapsing and continue as a **splanchnic nerve** to a prevertebral (collateral) ganglion located closer to the target organs.

#### Prevertebral (Collateral) Ganglia

The prevertebral ganglia are located anterior to the vertebral column, near the major abdominal arteries. The **celiac ganglion** receives the greater splanchnic nerve (carrying fibers from T5-T9) and sends postganglionic fibers to the stomach, liver, spleen, kidneys, and small intestine. The **superior mesenteric ganglion** receives the lesser splanchnic nerve (T10-T11) and supplies the small intestine and proximal colon. The **inferior mesenteric ganglion** receives the least splanchnic nerve (T12) and lumbar splanchnic nerves, supplying the distal colon, rectum, bladder, and reproductive organs.

#### Adrenal Medulla

The adrenal medulla represents a modified sympathetic ganglion in which the medulla itself serves as the "postganglionic" structure. Preganglionic sympathetic fibers from the greater splanchnic nerve synapse directly on chromaffin cells within the medulla. Rather than sending axons to effector organs, chromaffin cells release **epinephrine (approximately 80%) and norepinephrine (approximately 20%)** directly into the bloodstream. These hormones circulate throughout the body, amplifying and prolonging the sympathetic response. This arrangement explains why the sympathetic response can be widespread and long-lasting, functioning as a combined neural and hormonal ("sympathoadrenal") response.

<image>An overview diagram of the sympathetic division. On the left, the spinal cord is shown with lateral horns labeled from T1 to L2. Preganglionic neurons (shown in red) exit via ventral roots and white rami communicantes to reach the sympathetic trunk (a chain of paravertebral ganglia running alongside the vertebral column). Three pathways are illustrated: (1) synapse at the same level with a postganglionic fiber returning via the gray ramus communicans to a spinal nerve supplying skin blood vessels and sweat glands, (2) ascend within the trunk to a superior cervical ganglion supplying the head (dilated pupil, salivary glands), and (3) pass through the trunk as splanchnic nerves (greater, lesser, least) to prevertebral ganglia (celiac, superior mesenteric, inferior mesenteric) near the aorta, with postganglionic fibers reaching abdominal and pelvic organs. A separate arrow shows the greater splanchnic nerve going to the adrenal medulla, where chromaffin cells release epinephrine and norepinephrine into the blood. All preganglionic fibers are labeled "ACh" and postganglionic fibers are labeled "NE" (with the adrenal medulla labeled "Epi/NE into blood").</image>

### V. The Parasympathetic Division (Craniosacral Division)

#### Origin

Preganglionic cell bodies of the parasympathetic division are located in **brainstem nuclei** associated with cranial nerves III, VII, IX, and X, as well as in the **lateral gray matter of sacral spinal cord segments S2 through S4**. This dual origin gives rise to its alternative name, the **craniosacral division**.

#### Cranial Outflow

The cranial outflow is distributed through four cranial nerves. **CN III (Oculomotor)** sends preganglionic fibers that synapse in the **ciliary ganglion**, from which postganglionic fibers innervate the sphincter pupillae muscle for pupil constriction and the ciliary muscle for accommodation. **CN VII (Facial)** sends preganglionic fibers to the **pterygopalatine ganglion**, which supplies the lacrimal gland and nasal and palatal glands, and to the **submandibular ganglion**, which supplies the submandibular and sublingual salivary glands. **CN IX (Glossopharyngeal)** sends preganglionic fibers to the **otic ganglion**, from which postganglionic fibers innervate the parotid salivary gland.

The **vagus nerve (CN X)** is the single most important parasympathetic nerve, providing approximately 75% of all parasympathetic fibers. Its preganglionic fibers are very long, traveling from the brainstem all the way to **terminal (intramural) ganglia** located in or near the walls of the target organs, making the postganglionic fibers very short. The vagus innervates the heart, lungs, esophagus, stomach, small intestine, liver, gallbladder, pancreas, kidneys, and the proximal colon up to the splenic flexure.

#### Sacral Outflow

Preganglionic cell bodies in the lateral gray matter of **S2 through S4** send preganglionic fibers that form the **pelvic splanchnic nerves**. These fibers synapse in terminal ganglia near or within the walls of pelvic organs, innervating the distal colon, rectum, bladder, and reproductive organs.

#### Key Anatomical Feature

A fundamental anatomical distinction between the two divisions concerns ganglion location. Parasympathetic ganglia are located **close to or within the target organ**, resulting in long preganglionic fibers and short postganglionic fibers. Sympathetic ganglia, by contrast, are located **close to the spinal cord** (either paravertebral or prevertebral), resulting in short preganglionic fibers and long postganglionic fibers.

### VI. Neurotransmitters and Receptors

#### Cholinergic Neurons (Release ACh)

Cholinergic neurons include all preganglionic neurons of both sympathetic and parasympathetic divisions, all parasympathetic postganglionic neurons, the sympathetic postganglionic neurons that innervate sweat glands (an important exception to the general rule), and certain sympathetic postganglionic neurons innervating blood vessels in skeletal muscle where they produce vasodilation.

#### Cholinergic Receptors

Two major classes of cholinergic receptors exist. **Nicotinic receptors** are found on all postganglionic neuron cell bodies in autonomic ganglia and at the neuromuscular junction. They function as ligand-gated ion channels and are always excitatory. **Muscarinic receptors** are found on the target organs of parasympathetic postganglionic neurons and on sweat glands. They are G-protein-coupled receptors that can be either excitatory or inhibitory depending on the organ. The M1, M3, and M5 subtypes are excitatory (Gq-coupled), while the M2 and M4 subtypes are inhibitory (Gi-coupled). The M2 receptor on the heart is clinically important because it mediates the slowing of heart rate.

#### Adrenergic Neurons (Release NE)

Most sympathetic postganglionic neurons are adrenergic, releasing norepinephrine at their target organs.

#### Adrenergic Receptors

Adrenergic receptors are divided into alpha and beta subtypes. **Alpha-1 (α1)** receptors are found primarily on blood vessel smooth muscle and other smooth muscle, where they are generally excitatory, mediating vasoconstriction, pupil dilation, and urinary sphincter contraction. **Alpha-2 (α2)** receptors serve mainly as presynaptic autoreceptors providing negative feedback to inhibit further NE release, though they are also found on some smooth muscle and platelets. **Beta-1 (β1)** receptors are located primarily on the heart and increase heart rate (chronotropic effect), force of contraction (inotropic effect), and conduction velocity. **Beta-2 (β2)** receptors are found primarily on bronchial smooth muscle and some blood vessels, where they mediate relaxation, producing bronchodilation and vasodilation in skeletal muscle arterioles. **Beta-3 (β3)** receptors are located on adipose tissue and stimulate lipolysis.

<image>A comparison diagram of sympathetic and parasympathetic pathways side by side. On the left (Sympathetic), the pathway shows: preganglionic neuron (short, myelinated, from T1-L2 lateral horn) releasing ACh onto nicotinic receptors at a paravertebral or prevertebral ganglion. The postganglionic neuron (long, unmyelinated) releases NE onto alpha or beta adrenergic receptors on the target organ (with exceptions noted: ACh to sweat glands via muscarinic receptors, and the adrenal medulla releasing Epi/NE into the blood). On the right (Parasympathetic), the pathway shows: preganglionic neuron (long, myelinated, from brainstem CN III/VII/IX/X or S2-S4) releasing ACh onto nicotinic receptors at a terminal ganglion near/in the target organ. The postganglionic neuron (short, unmyelinated) releases ACh onto muscarinic receptors on the target organ. A central table compares the two divisions across categories: origin, ganglion location, fiber length, neurotransmitters, receptors, and general effects.</image>

### VII. Dual Innervation and Effects on Target Organs

Most visceral organs receive innervation from both the sympathetic and parasympathetic divisions, a pattern known as **dual innervation**. The two divisions generally produce **opposing effects**, creating a dynamic antagonism that allows fine-tuned control. At rest, one division typically dominates: **sympathetic tone** maintains blood vessel diameter, while **parasympathetic (vagal) tone** dominates resting heart rate.

| Organ/Target | Sympathetic Effect | Parasympathetic Effect |
|---|---|---|
| **Heart** | Increases rate and force (β1) | Decreases rate (M2); slight decrease in atrial contractility |
| **Blood vessels** | Vasoconstriction (α1) — most vessels; vasodilation (β2) — skeletal muscle | Little direct effect on most vessels (no parasympathetic innervation to most arterioles) |
| **Lungs (bronchioles)** | Bronchodilation (β2) | Bronchoconstriction (M3); increased mucus secretion |
| **Pupils** | Dilation — mydriasis (α1 on dilator pupillae) | Constriction — miosis (M3 on sphincter pupillae) |
| **GI tract motility** | Decreases motility and secretion (α2, β2) | Increases motility and secretion (M3) |
| **GI sphincters** | Contraction (α1) — closes sphincters | Relaxation (M3) — opens sphincters |
| **Salivary glands** | Thick, viscous, enzyme-rich secretion (α1); reduced volume | Profuse, watery secretion (M3) |
| **Sweat glands** | Stimulates secretion (ACh on muscarinic receptors — exception) | No innervation |
| **Adrenal medulla** | Stimulates Epi/NE release | No innervation |
| **Liver** | Glycogenolysis and gluconeogenesis (α1, β2) — increases blood glucose | Glycogen synthesis (minor) |
| **Bladder (detrusor)** | Relaxation (β2) — filling | Contraction (M3) — voiding |
| **Urinary sphincter (internal)** | Contraction (α1) — continence | Relaxation — allows voiding |
| **Reproductive organs** | Ejaculation, uterine contraction (α1) | Erection (vasodilation via NO release) |
| **Arrector pili muscles** | Contraction — goosebumps (α1) | No innervation |
| **Adipose tissue** | Lipolysis (β3) | No innervation |

Some structures receive innervation from only one division. The adrenal medulla, sweat glands, arrector pili muscles, most blood vessels, and kidneys (for renin release) are innervated exclusively by the sympathetic division, while the lacrimal glands are primarily innervated by the parasympathetic division alone.

### VIII. Sympathetic "Fight-or-Flight" Response

The sympathetic division is activated during stress, exercise, excitement, and emergency situations, producing a coordinated, body-wide response. Heart rate, contractility, and blood pressure all increase. Blood flow is redistributed away from the GI tract and skin and toward skeletal muscles, heart, and brain. The airways undergo bronchodilation to increase airflow, while the pupils dilate to improve far vision. Metabolically, blood glucose rises through glycogenolysis and gluconeogenesis. Sweating increases to dissipate heat, and digestion and urination are inhibited. The release of epinephrine and norepinephrine from the adrenal medulla amplifies and prolongs this entire response.

### IX. Parasympathetic "Rest-and-Digest" Response

The parasympathetic division dominates during calm, non-stressful conditions and promotes energy conservation and restorative processes. Heart rate decreases, and digestion is stimulated through increased GI motility, secretion, and sphincter relaxation. Salivation and lacrimation are stimulated, the pupil constricts for near vision, the bladder contracts for micturition, and energy is conserved and stored. Sexual arousal, specifically erection, is also mediated by the parasympathetic division.

### X. Higher-Level Control of the ANS

The autonomic nervous system does not operate independently but is regulated by higher centers in the CNS. The **hypothalamus** serves as the main integration center, coordinating sympathetic and parasympathetic outflow with endocrine, behavioral, and emotional responses. The **brainstem** houses cardiovascular and respiratory centers in the medulla as well as reflex centers. The **cerebral cortex** provides some conscious influence, as when anxiety increases heart rate or when biofeedback techniques allow limited voluntary control. The **limbic system** channels emotional influences into autonomic function, producing effects such as blushing or "butterflies in the stomach." Finally, the **spinal cord** contains reflex arcs for micturition, defecation, and erection.

### XI. Clinical Correlations

#### Autonomic Dysreflexia

Autonomic dysreflexia is a life-threatening condition that can occur in patients with spinal cord injuries above T6. A noxious stimulus below the level of the injury triggers a massive, uncontrolled sympathetic response, resulting in severe hypertension accompanied by bradycardia due to a compensatory vagal response above the lesion. Emergency management involves removing the offending stimulus, sitting the patient upright, and treating the hypertension.

#### Pharmacological Targets

Many commonly used drugs target autonomic receptors. Beta-blockers such as propranolol and metoprolol block β1 receptors and are used to reduce heart rate and blood pressure. Atropine blocks muscarinic receptors, increasing heart rate by removing vagal slowing and dilating the pupils. Epinephrine (as in the EpiPen) activates both α and β receptors and is used in anaphylaxis to produce bronchodilation, vasoconstriction, and increased cardiac output. Albuterol is a selective β2 agonist that produces bronchodilation in asthma.

#### Horner Syndrome

Horner syndrome results from disruption of the sympathetic pathway to the face, such as damage to the superior cervical ganglion or its connections. The classic triad consists of ipsilateral **miosis** (constricted pupil), **ptosis** (drooping eyelid due to loss of sympathetic innervation to the superior tarsal muscle), and **anhidrosis** (absence of sweating on the affected side of the face).