Chapter 20: The Autonomic Nervous System

The autonomic (visceral) nervous system (ANS) is concerned with control of target tissues: the cardiac muscle, the smooth muscle in blood vessels and viscera, and the glands. It helps maintain a constant internal body environment (homeostasis). The ANS consists of efferent pathways, afferent pathways, and groups of neurons in the brain and spinal cord that regulate the system's functions. It is modulated by supraspinal centers such as brain stem nuclei and the hypothalamus.

The ANS is divided into two major anatomically distinct divisions with opposing actions: the sympathetic (thoracolumbar) and parasympathetic (craniosacral) divisions (Fig 20–1). The sympathetic and parasympathetic divisions of the ANS are anatomically distinct, and are different in terms of their pharmacological properties, that is, their response to medications. They are sometimes referred to as the sympathetic nervous system and the parasympathetic nervous system. Many commonly used medications (eg, medications for treating high blood pressure, for regulating gastrointestinal function, or for maintaining a regular heart beat) have their major actions on neurons within these systems.

Some authorities consider the intrinsic neurons of the gut as forming a separate enteric nervous system.

The efferent components of the autonomic system are organized into sympathetic and parasympathetic divisions, which arise from preganglionic cell bodies in different locations.

The autonomic outflow system is organized more diffusely than the somatic motor system. In the somatic motor system, lower motor neurons project directly from the spinal cord or brain, without an interposed synapse, to innervate a relatively small group of target cells (somatic muscle cells). This permits individual muscles to be activated separately so that motor action is finely tuned. In contrast, a more slowly conducting two-neuron chain characterizes the autonomic outflow. The cell body of the primary neuron (the presynaptic, or preganglionic, neuron) within the central nervous system is located in the intermediolateral gray column of the spinal cord or in the brain stem nuclei. It sends its axon, which is usually a small-diameter, myelinated B fiber (see Chapter 3), out to synapse with the secondary neuron (the postsynaptic, or postganglionic, neuron) located in one of the autonomic ganglia. From there, the postganglionic axon passes to its terminal distribution in a target organ. Most postganglionic autonomic axons are unmyelinated C fibers.

The autonomic outflow system projects widely to most target tissues and is not as highly focused as the somatic motor system. Because the postganglionic fibers outnumber the preganglionic neurons by a ratio of about 32:1, a single preganglionic neuron may control the autonomic functions of a rather extensive terminal area.

Sympathetic Division

The sympathetic nervous system, or sympathetic (thoracolumbar) division of the ANS arises from preganglionic cell bodies located in the intermediolateral cell columns of the 12 thoracic segments and the upper two lumbar segments of the spinal cord (Fig 20–2).

A. Preganglionic Sympathetic Efferent Fiber System

Preganglionic fibers are mostly myelinated. Coursing with the ventral roots, they form the white communicating rami of the thoracic and lumbar nerves, through which they reach the ganglia of the sympathetic chains or trunks (Fig 20–3). These trunk ganglia lie on the lateral sides of the bodies of the thoracic and lumbar vertebrae. On entering the ganglia, the fibers may synapse with ganglion cells, pass up or down the sympathetic trunk to synapse with ganglion cells at a higher or lower level, or pass through the trunk ganglia and out to one of the collateral (intermediary) sympathetic ganglia (eg, the celiac and mesenteric ganglia).

The splanchnic nerves arising from the lower seven thoracic segments pass through the trunk ganglia to the celiac and superior mesenteric ganglia. There, synaptic connections occur with ganglion cells whose postganglionic axons then pass to the abdominal viscera via the celiac plexus. The splanchnic nerves arising from spinal cord segments in the lowest thoracic and upper lumbar region convey fibers to synaptic stations in the inferior mesenteric ganglion and to small ganglia associated with the hypogastric plexus, through which postsynaptic fibers are distributed to the lower abdominal and pelvic viscera.

B. The Adrenal Gland

Preganglionic sympathetic axons in the splanchnic nerves also project to the adrenal gland, where they synapse on chromaffin cells in the adrenal medulla. The adrenal chromaffin cells, which receive direct synaptic input from preganglionic sympathetic axons, are derived from neural crest and can be considered to be modified postganglionic cells that have lost their axons.

C. Postganglionic Efferent Fiber System

The mostly unmyelinated postganglionic sympathetic fibers form the gray communicating rami. The fibers may course with the spinal nerve for some distance or go directly to their target tissues.

The gray communicating rami join each of the spinal nerves and distribute the vasomotor, pilomotor, and sweat gland innervation throughout the somatic areas. Branches of the superior cervical sympathetic ganglion enter into the formation of the sympathetic carotid plexuses around the internal and external carotid arteries for distribution of sympathetic fibers to the head (Fig 20–4). After exiting from the carotid plexus, these postganglionic sympathetic axons project to the salivary and lacrimal glands, the muscles that dilate the pupil and raise the eyelid, and sweat glands and blood vessels of the face and head.

The superior cardiac nerves from the three pairs of cervical sympathetic ganglia pass to the cardiac plexus at the base of the heart and distribute cardioaccelerator fibers to the myocardium. Vasomotor branches from the upper five thoracic ganglia pass to the thoracic aorta and to the posterior pulmonary plexus, through which dilator fibers reach the bronchi.

Parasympathetic Division

The parasympathetic nervous system or parasympathetic (craniosacral) division of the ANS arises from preganglionic cell bodies in the gray matter of the brain stem (medial part of the oculomotor nucleus, Edinger–Westphal nucleus, superior and inferior salivatory nuclei) and the middle three segments of the sacral cord (S2–4) (Figs 20–3 and 20–5). Most preganglionic fibers from S2, S3, and S4 run without interruption from their central origin within the spinal cord to either the wall of the viscus they supply or the site where they synapse with terminal ganglion cells associated with the plexuses of Meissner and Auerbach in the wall of the intestinal tract (see Enteric Nervous System section). Because the parasympathetic postganglionic neurons are located close to the tissues they supply, they have relatively short axons. The parasympathetic distribution is confined entirely to visceral structures.

Four cranial nerves convey preganglionic parasympathetic (visceral efferent) fibers. The oculomotor, facial, and glossopharyngeal nerves (cranial nerves III, VII, and IX) distribute parasympathetic or visceral efferent fibers to the head (see Fig 20–4 and Chapters 7 and 8). Parasympathetic axons in these nerves synapse with postganglionic neurons in the ciliary, sphenopalatine, submaxillary, and otic ganglia, respectively (see Autonomic Innervation of the Head section).

The vagus nerve (cranial nerve X) distributes its autonomic fibers to the thoracic and abdominal viscera via the prevertebral plexuses. The pelvic nerve (nervus erigentes) distributes parasympathetic fibers to most of the large intestine and to the pelvic viscera and genitals via the hypogastric plexus.

Autonomic Plexuses

The autonomic plexuses are a large network of nerves that serve a conduit for the distribution of the sympathetic and parasympathetic (and afferent) fibers that enter into their formation (see Figs 20–1, 20–2, and 20–5).

The cardiac plexus, located about the bifurcation of the trachea and roots of the great vessels at the base of the heart, is formed from the cardiac sympathetic nerves and cardiac branches of the vagus nerve, which it distributes to the myocardium and the vessels leaving the heart.

The right and left pulmonary plexuses are joined with the cardiac plexus and are located about the primary bronchi and pulmonary arteries at the roots of the lungs. They are formed from the vagus and the upper thoracic sympathetic nerves and are distributed to the vessels and bronchi of the lung.

The celiac (solar) plexus is located in the epigastric region over the abdominal aorta. It is formed from vagal fibers reaching it via the esophageal plexus, sympathetic fibers arising from celiac ganglia, and sympathetic fibers coursing down from the thoracic aortic plexus. It projects to abdominal viscera, by way of numerous subplexuses, including phrenic, hepatic, splenic, superior gastric, suprarenal, renal, spermatic or ovarian, abdominal aortic, and superior and inferior mesenteric plexuses.

The hypogastric plexus is located in front of the fifth lumbar vertebra and the promontory of the sacrum. It receives sympathetic fibers from the aortic plexus and lumbar trunk ganglia and parasympathetic fibers from the pelvic nerve. Its two lateral portions, the pelvic plexuses, lie on either side of the rectum. It projects to the pelvic viscera and genitals via subplexuses that extend along the visceral branches of the hypogastric artery. These subplexuses include the middle hemorrhoidal plexus, to the rectum; the vesical plexus, to the bladder, seminal vesicles, and ductus deferens; the prostatic plexus, to the prostate, seminal vesicles, and penis; the vaginal plexus, to the vagina and clitoris; and uterine plexus, to the uterus and uterine tubes.

The autonomic system supplies visceral structures in the head (see Fig 20–4). The skin of the face and scalp (smooth muscle, glands, and vessels) receives postsynaptic sympathetic innervation only, from the superior cervical ganglion via the carotid plexus, which extends along the branches of the external carotid artery. The deeper structures (intrinsic eye muscles, salivary glands, and mucous membranes of the nose and pharynx) receive a dual autonomic supply from the sympathetic and parasympathetic divisions, mediated by the internal carotid plexus (postganglionic sympathetic innervation from the superior cervical plexus) and the visceral efferent fibers in four pairs of cranial nerves (parasympathetic innervation).

There are four pairs of autonomic ganglia—ciliary, pterygopalatine, otic, and submaxillary—in the head (see Fig 20–4). Each ganglion receives a sympathetic, a parasympathetic, and a sensory root (a branch of the trigeminal nerve). Only the parasympathetic fibers make synaptic connections within these ganglia, which contain the cell bodies of the postganglionic parasympathetic fibers. The sympathetic and sensory fibers pass through these ganglia without interruption.

The ciliary ganglion is located between the optic nerve and the lateral rectus muscle in the posterior orbit. Its parasympathetic root originates from cells in or near the Edinger–Westphal nucleus of the oculomotor nerve. Its sympathetic root is composed of postganglionic fibers from the superior cervical sympathetic ganglion via the carotid plexus of the internal carotid artery. The sensory root comes from the nasociliary branch of the ophthalmic nerve. Distribution is through 10 to 12 short ciliary nerves that supply the ciliary muscle of the lens and the constrictor muscle of the iris. The dilator muscle of the iris is supplied by sympathetic nerves.

The sphenopalatine (pterygopalatine) ganglion, located deep in the pterygopalatine fossa, is associated with the maxillary nerve. Its parasympathetic root arises from cells of the superior salivatory nucleus via the glossopalatine nerve and the great petrosal nerve. The ganglion's sympathetic root comes from the internal carotid plexus by way of the deep petrosal nerve, which joins the great superficial petrosal nerve to form the vidian nerve in the pterygoid (vidian) canal. Most of the sensory root fibers originate in the maxillary nerve, but a few arise in cranial nerves VII and IX via the tympanic plexus and vidian nerve. Distribution is through the pharyngeal rami to the mucous membranes of the roof of the pharynx; via the nasal and palatine rami to the mucous membranes of the nasal cavity, uvula, palatine tonsil, and hard and soft palates; and by way of the orbital rami to the periosteum of the orbit and the lacrimal glands.

The otic ganglion is located medial to the mandibular nerve just below the foramen ovale in the infratemporal fossa. Its parasympathetic root fibers arise in the inferior salivatory nucleus in the medulla and course via cranial nerve IX, the tympanic plexus, and the lesser superficial petrosal nerve; the sympathetic root comes from the superior cervical sympathetic ganglion via the plexus on the middle meningeal artery. Its sensory root probably includes fibers from cranial nerve IX and from the geniculate ganglion of cranial nerve VII via the tympanic plexus and the lesser superficial petrosal nerve. The otic ganglion supplies secretory and sensory fibers to the parotid gland. A few somatic motor fibers from the trigeminal nerve pass through the otic ganglion and supply the tensor tympani and tensor veli palatini muscles.

The submaxillary ganglion is located on the medial side of the mandible between the lingual nerve and the submaxillary duct. Its parasympathetic root fibers arise from the superior salivatory nucleus of nerve VII via the glossopalatine, chorda tympani, and lingual nerves; its sympathetic root, from the plexus of the external maxillary artery; and its sensory root, from the geniculate ganglion via the glossopalatine, chorda tympani, and lingual nerves. It is distributed to the submaxillary and sublingual glands.

Visceral afferent fibers have their cell bodies in sensory ganglia of some of the cranial and spinal nerves. Although a few of these fibers are myelinated, most are unmyelinated and have slow conduction velocities. The pain innervation of the viscera is summarized in Table 20–1.

Pathways to the Spinal Cord

Visceral afferent fibers to the spinal cord enter by way of the middle sacral, thoracic, and upper lumbar nerves. The sacral nerves carry sensory stimuli from the pelvic organs, and the nerve fibers are involved in reflexes of the sacral parasympathetic outflow that control various sexual responses, micturition, and defecation. Axons carrying visceral pain impulses from the heart, upper digestive tract, kidney, and gallbladder travel with the thoracic and upper lumbar nerves. These visceral afferent pathways are associated with sensations such as hunger, nausea, and visceral pain (see Table 20–1). Pain impulses from a viscus may converge with pain impulses arising in a particular region of the skin, causing referred pain. Examples of the phenomenon are the shoulder pains associated with gallstone attacks and pain of the left arm or throat associated with myocardial ischemia (see Chapter 14).

Pathways to the Brain Stem

Visceral afferent axons in the glossopharyngeal nerve and especially the vagus nerve carry a variety of sensations to the brain stem from the heart, great vessels, and respiratory and gastrointestinal tracts. The ganglia involved are the inferior glossopharyngeal nerve ganglion and the inferior vagus nerve ganglion (formerly called the nodose ganglion). The afferent fibers are also involved in reflexes that regulate blood pressure, respiratory rate and depth, and heart rate through specialized receptors or receptor areas. These baroreceptors, which are stimulated by pressure, are located in the aortic arch and carotid sinus (Fig 20–8). Chemoreceptors that are sensitive to hypoxia are located in the aorta and carotid bodies. A chemosensitive area is located in the medulla and contains chemoreceptor neurons that alter their firing patterns in response to alterations of pH and pCO₂ within the cerebrospinal fluid.

The hierarchical structure of the brain and spinal cord applies to the autonomic system. This hierarchy exerts its influence, at several levels along the rostrocaudal axis, on visceral reflexes.

Spinal Cord

Autonomic reflexes such as peristalsis and micturition are mediated by the spinal cord, but descending pathways from the brain modify, inhibit, or initiate the reflexes (Fig 20–9). This is illustrated by the autonomic innervation that controls the urinary bladder. Bladder control centers on a primitive reflex loop involving parasympathetic preganglionic neurons located at the S2, S3, and S4 levels of the spinal cord. When excited by sensory impulses signaling that the bladder is dilated, these parasympathetic neurons send impulses that excite the detrusor muscle and inhibit the urinary sphincters, thus emptying the bladder in a reflex manner. This primitive detrusor reflex accounts for urinary function in infants. After early childhood, this reflex is modulated by descending influences, including voluntary sphincter release, which begins urination, and suppression, which retards urination.

Control of urination may be impaired in patients who have had a transection of the spinal cord. Spinal shock develops, and hypotension and loss of reflexes govern micturition and defecation. Although the reflexes return after a few days or weeks, they may be incomplete or abnormal. For example, often the bladder cannot be completely emptied, which may result in cystitis, and voluntary initiation of micturition may be absent (autonomic or neurogenic bladder). Depending on the level of the transection, the detrusor reflex may be hyperactive or diminished, and the neurogenic bladder may be spastic or flaccid (Figs 20–10 and 20–11).

Medulla

Medullary connections to and from the spinal cord are lightly myelinated fibers of the tractus proprius around the gray matter of the cord. Visceral afferent fibers of the glossopharyngeal and vagus nerves terminate in the solitary tract nucleus and are involved in control of respiratory, cardiovascular, and alimentary functions (see Chapters 7 and 8). The major reflex actions have connections with visceral efferent nuclei of the medulla and areas of the reticular formation. These areas may contribute to the regulation of blood glucose levels and to other reflex functions, including salivation, micturition, vomiting, sneezing, coughing, and gagging.

Pons

The nucleus parabrachialis is a group of neurons located near the superior cerebellar peduncle that modulates the medullary neurons responsible for rhythmic respiration. This pneumotaxic center continues to control periodic respiration if the brain stem is transected between the pons and the medulla.

Midbrain

Accommodation, pupillary reactions to light, and other reflexes are integrated in the midbrain, near the nuclear complex of nerve III. Pathways from the hypothalamus to the visceral efferent nuclei in the brain stem course through the dorsal longitudinal fasciculus in the periaqueductal and periventricular gray matter.

Hypothalamus

The hypothalamus integrates autonomic activities in response to changes in the internal and external environments (thermoregulatory mechanisms; see Chapter 9). The posterior portion of the hypothalamus is involved with sympathetic function, and the anterior portion is involved with parasympathetic function. The most important descending pathway is the dorsal longitudinal fasciculus. The connections with the hypophysis aid in the influence of the hypothalamus on visceral functions.

Limbic System

The limbic system has been called the visceral brain and has close anatomic and functional links with the hypothalamus (see Chapter 19). The limbic system exert control over the visceral manifestations of emotion and drives such as sexual behavior, fear, rage, aggression, and eating behavior. Stimulation of limbic system areas elicits such autonomic reactions as cardiovascular and gastrointestinal responses, micturition, defecation, piloerection, and pupillary changes. These reactions are channeled, in large part, through the hypothalamus.

Cerebral Neocortex

The cerebral neocortex may initiate autonomic reactions such as blushing or blanching of the face in response to receiving bad or good news. Fainting (syncope) because of hypotension or decreased heart rate can result from a barrage of vagal activity evoked by an emotional stimulus.

The Enteric Nervous System

A collection of neurons associated with the gut, sometimes considered to be an "intrinsic nervous system of the gastrointestinal tract," can function relatively independently of the central nervous system but subject to modulation from it. This loose meshwork of neurons, which regulates gastrointestinal motility, secretory activity, vascular activity, and inflammation, has been termed the enteric nervous system. The enteric nervous system contains nearly 100 million neurons located within numerous small ganglia. These ganglia are interconnected, via nerve bundles, to form two networks (plexuses). The first of these is the myenteric plexus (also called Auerbach's plexus), which is located between the muscular layers that make up the gastrointestinal system, from the esophagus at the rostral end to the rectum at the caudal end. Additional projections to smaller ganglia are also associated with the pancreas and gallbladder. The submucosa plexus, also called Meissner's plexus, is largely confined to the submucosa of the gut and is most prominent within the small intestine, where it regulates secretory activity and innervates blood vessels. Counterparts of the submucous plexus innervate the pancreas, gallbladder, common bile duct, and cystic duct.

Enteric neurons innervate smooth muscle cells that are responsible for gut motility as well as secretory and endocrine cells in the gut and its vasculature. The activity of enteric neurons is modulated by the parasympathetic nervous system and the sympathetic nervous system. Parasympathetic control pathways run largely in the vagus nerves (for the upper gastrointestinal tract) and the sacral nerves (which modulate functions such as contractility of the lower colon and rectum). Most of the preganglionic parasympathetic neurons are cholinergic and act on enteric neurons via excitatory nicotinic and muscarinic receptors. Preganglionic sympathetic fibers projecting to the gastrointestinal tract, on the other hand, are adrenergic.

Sensory information from the gastrointestinal system is carried to the central nervous system in the vagus and splanchnic nerves via primary afferent neurons whose cell bodies are located in the nodose ganglia.

Types

Autonomic activity controls many essential body functions. Pharmacology and pharmacotherapy depend, in large part, on our understanding of the neurochemistry of the autonomic system since many medication act so as to increase, on block, activity in various parts of the autonomic system.

Autonomic neurotransmitters mediate multiple visceral functions; the principal transmitter agents are acetylcholine (ACh) and norepinephrine (see Chapter 3). The two divisions of the autonomic system (parasympathetic and sympathetic) tend to release different transmitters (ACh and norepinephrine) from their postganglionic neurons (although there are several exceptions, noted later), providing a pharmacologic basis for their opposing actions.

ACh is liberated at preganglionic endings. It is also released by parasympathetic postganglionic neurons and by sympathetic postganglionic neurons that project to sweat glands or mediate vasodilation.

Norepinephrine, a catecholamine, is the transmitter at most sympathetic postganglionic endings. Norepinephrine and its methyl derivative, epinephrine, are secreted by the adrenal medulla. Although many viscera contain both norepinephrine and epinephrine, the latter is not considered to be a mediator at sympathetic endings. Drugs that block the effects of epinephrine but not norepinephrine have little effect on the response of most organs to stimulation of their adrenergic nerve supply.

Substance P, somatostatin, vasoactive intestinal peptide (VIP), adenosine, and adenosine triphosphate (ATP) may also function as visceral neurotransmitters.

Functions

The ANS can be divided into cholinergic and adrenergic divisions. Cholinergic neurons include preganglionic and parasympathetic postganglionic neurons, sympathetic postganglionic neurons to sweat glands, and sympathetic vasodilator neurons to blood vessels in skeletal muscle. There is usually no ACh in circulating blood, and the effects of localized cholinergic discharge are generally discrete and short lived because of high concentrations of cholinesterase at the cholinergic nerve endings (Fig 20–12 and Table 20–2).

In the adrenal medulla, the postganglionic cells have lost their axons and become specialized for secreting catecholamine (epinephrine) directly into the blood; the cholinergic preganglionic neurons to these cells act as the secretomotor nerve supply to the adrenal gland. Sympathetic postganglionic neurons are generally considered adrenergic except for the sympathetic vasodilator neurons and sweat gland neurons. Norepinephrine has a more prolonged and wider action than does ACh.

Receptors

The target tissues on which norepinephrine acts can be separated into two categories, based on their different sensitivities to certain drugs. This is related to the existence of two types of catecholamine receptors—α and β—in the target tissues. The α receptors mediate vasoconstriction, and the β receptors mediate such actions as the increase in cardiac rate and the strength of cardiac contraction. There are two subtypes of α receptors (α₁ and α₂) and two subtypes of β receptors (β₁ and β₂). The α and β receptors occur in both preganglionic endings and postganglionic membranes. The preganglionic β-adrenergic receptors are of the β₁ type; the postganglionic receptors are of the β₂ type (Fig 20–13 and Table 20–2).

Despite apparent similarities in the transmitter chemistry of preganglionic and postganglionic cholinergic neurons, agents can act differently at these sites. Muscarine has little effect on autonomic ganglia, for example, but acts on smooth muscle and glands, where it mimics the effects of ACh. The ACh receptors on these cells are termed muscarinic. Drugs with muscarinic action include ACh, ACh-related substances, and inhibitors of cholinesterase (eg, certain nerve gases). Atropine, belladonna, and other natural and synthetic belladonna-like drugs block the muscarine effects of ACh by preventing the mediator from acting on visceral effector organs.

Some actions of ACh, including the transmission of impulses from preganglionic to postganglionic neurons, are not affected by atropine. Because nicotine produces the same actions, the actions of ACh in the presence of atropine are called its nicotine effects, and the receptors are called nicotinic acetylcholine receptors. Nicotinic acetylcholine receptors are present at neuromuscular junctions and at the synapses between preganglionic and postganglionic neurons.

Curariform agents, hexamethonium, and mecamylamine act principally by blocking transmission at the cholinergic motor neuron endings on skeletal muscle fibers. They were used in the past in the treatment of hypertension.

Drugs that block the effects of norepinephrine on visceral effectors are often called adrenergic-neuron–blocking agents, adrenolytic agents, or sympatholytic agents.

Sensitization

Autonomic effectors (smooth muscle, cardiac muscle, and glands) that are partially or completely separated from their normal nerve connections become more sensitive to the action of the neurotransmitters that normally impinge on them; this has been termed denervation hypersensitivity.