Autonomic Nervous System and Its Disorders

General Topography of Autonomic Nervous System

The nervous system is divided into somatic and autonomic divisions: the somatic division controls predominantly voluntary activities, while the autonomic system regulates involuntary functions. The two divisions develop from the same primordial cells; they comprise closely associated central and peripheral components and are both built up from afferent, efferent, and interneurons linked to produce ascending and descending nerve pathways and reflex arcs.

The central autonomic components include regions of the cerebral cortex, diencephalon, and brainstem. In the cerebral cortex, autonomic areas include the frontal premotor areas, telencephalic cortex in the hippocampus, insular cortex, anterior cingulate gyrus, and anteromedial prefrontal cortex. The central nucleus of the amygdala and the bed nucleus of the stria terminalis are known as the extended amygdala and modulate the autonomic responses to emotions.

The hypothalamus integrates autonomic and endocrine responses and includes nuclei in three functional zones: periventricular, lateral, and medial. Nuclei in the periventricular region control biologic rhythms; the suprachiasmatic nucleus, the pacemaker for the circadian rhythms, and the paraventricular nuclei are involved in endocrine responses by modulating the anterior pituitary. The lateral hypothalamic nuclei are involved in arousal and behavior, whereas the medial hypothalamic area, including the medial preoptic region, is involved in homeostatic functions such as thermoregulation. The periaqueductal gray nuclei of the midbrain integrate autonomic and behavioral response to nociceptive environmental stimuli. The parabrachial nucleus of the pons and the nucleus of tractus solitarius in the medulla are the principal relay nuclei in the control of cardiovascular, respiratory, and visceral function in response to environmental stimuli. The reticular formation of the anterolateral medulla contains the primary premotor neurons that control the respiratory motor neurons of the brainstem and cervical spinal cord as well as the sympathetic neurons in the intermediolateral column of the thoracic spinal cord.

These higher and lower levels of representation are interconnected by ascending and descending tracts, or pathways. For example, efferent autonomic inputs originating in the frontal premotor cortical areas descend through fasciculi, usually via synaptic relays in the thalamus, hypothalamus, and reticular formation, and end in certain cranial nerve nuclei and thus influence involuntary muscles, blood vessels, and exocrine and endocrine glands supplied by them. Other fibers descend still farther and form synapses with neurons in the intermediolateral columns in the thoracic and upper two lumbar spinal cord segments, and with neurons in the gray matter of the second to fourth sacral cord segments.

Afferents to the central autonomic area is conveyed by cranial and spinal pathways. Afferent innervation from baroreceptors, chemoreceptors, and pulmonary and gastrointestinal autonomic receptors is conveyed by the vagus and glossopharyngeal nerves to the nucleus of the tractus solitarius. The information is relayed from this nucleus to the more rostral autonomic centers; visceral input and taste are relayed to the anteromedial nucleus of thalamus and then to the insular cortex. Humoral signals are relayed to the central autonomic areas by the circumventricular organs that lack a blood-brain barrier, such as the subfornical organ, the lamina terminalis in the third ventricle, and the area postrema.

The peripheral parts of the autonomic nervous system include sympathetic ganglia and the paravertebral sympathetic trunks, which extend from the cranial base to the coccyx. Other sympathetic and parasympathetic ganglia include the ciliary, pterygopalatine, otic, submandibular, and carotid in the cranial region; prevertebral plexuses and ganglia, such as the cardiac, celiac, mesenteric, aortic, and hypogastric; plexuses located on or in the walls of viscera and vessels; and ganglia associated with the liver and adrenal gland.

The axons of autonomic neurons in the cranial nerve nuclei and sacral spinal segments usually produce effects opposite to those produced by the axons of neurons in the thoracolumbar intermediolateral cell columns. The cranial and sacral groups comprise the parasympathetic system, and the more numerous thoracolumbar groups, the sympathetic system. The neurons of sympathetic and parasympathetic systems are morphologically similar; they are smallish, ovoid, multipolar cells with myelinated axons and variable number of dendrites.

The axons of the autonomic nerve cells in the nuclei of the cranial nerves, in the thoracolumbar intermediolateral columns, and in the gray matter of the sacral spinal segments are termed preganglionic fibers and form synapses in peripheral ganglia. The axons of the ganglion cells are called postganglionic fibers; these unmyelinated axons convey efferent output to the viscera, vessels, and other structures.

The cranial parasympathetic preganglionic fibers form synapses in the ciliary, pterygopalatine, otic, submandibular, cardiac, and celiac ganglia, and in much smaller ganglia in the walls of the trachea, bronchi, and gastrointestinal tract. The corresponding sacral fibers form synapses in the inferior hypogastric (pelvic) plexuses, within the enteric plexuses of the distal colon and rectum, and in the walls of the urinary bladder and other pelvic viscera. Most of the thoracolumbar sympathetic preganglionic fibers synapse in sympathetic trunk ganglia, but some fibers pass through the sympathetic trunk ganglia to form synapses in other ganglia, such as the celiac, mesenteric, and renal.

Parasympathetic relay ganglia are located near the structures innervated or within the walls of hollow organs or solid viscera; therefore parasympathetic postganglionic fibers are relatively short. Sympathetic relay ganglia are generally more distant from the structures they innervate, so sympathetic postganglionic fibers are often much longer than their parasympathetic counterparts. Plate 7-2 illustrates the arrangement of the preganglionic and postganglionic fibers to all the important viscera, the positions of the ganglia in which the synaptic relays occur, and the consequent disparities in the lengths of the postganglionic fibers. For example, in the heart, sympathetic preganglionic fibers synapse with the neurons in the superior cervical to the fifth thoracic sympathetic ganglia; the relatively long postganglionic fibers are conveyed to the heart in the cervical and thoracic sympathetic cardiac nerves. The parasympathetic preganglionic fibers reach the heart in the cardiac branches of the vagus nerves and relay in ganglia of the cardiac plexus or in small subendocardial ganglia; their postganglionic fibers are relatively short.

Autonomic Reflex Pathways

The illustration on the right shows the arrangement of a typical spinal autonomic reflex arc, in this example involving the enteric plexus in the gut. Similar reflex arcs exist in the brainstem.

The autonomic reflex arc is similar to the somatic reflex arc, although, in the somatic arcs, the interneurons and their connections are entirely within the central nervous system (CNS). In the autonomic arcs, the interneurons are within the CNS, but their axons synapse outside the CNS to reach the ganglia in which they terminate. Initially, the autonomic and somatic components of the nervous system develop together, but during the embryonic and fetal phases, groups of nerve cells migrate outward along the spinal nerve roots and form ganglia, such as those of the sympathetic trunks, and more peripheral ganglia, such as the celiac and mesenteric (see Plate 7-13 ). These migrant cells are efferent autonomic neurons, and in order to maintain their synaptic relationships, the axons of the interneurons must follow them, to reach the autonomic ganglion cells with which they form synapses. These axons are termed preganglionic fibers , whereas the axons of ganglionic neurons lie beyond the ganglia and are called postganglionic fibers.

The preganglionic fibers are myelinated, and when seen together, as in the large groups of sympathetic preganglionic fibers passing from all the thoracic and the upper two lumbar spinal nerves to nearby sympathetic trunk ganglia, they are almost white in color and constitute the white rami communicantes . Afferent myelinated fibers pass through these rami to the spinal nerves and contribute to their whitish appearance. The postganglionic fibers are unmyelinated and appear grayish pink in color when seen in mass. They form the gray rami communicantes connecting each sympathetic trunk ganglion to the adjoining spinal nerves.

One part of a parasympathetic arc (vagal) is illustrated; the efferent preganglionic fibers arise from the dorsal vagal nucleus and reach the walls of the intestine by vagal branches that are part of, and synapse with cells in the ganglia forming the enteric plexus; postganglionic fibers innervate the intestines. The cell bodies of the afferent pseudounipolar neurons are also located in afferent ganglia of the enteric plexus and their central axonal processes travel to the brainstem in the vagal nerve to synapse with the neurons in the dorsal vagal nuclei.

The illustration also shows that sympathetic preganglionic fibers emerge through the anterior root of the thoracic or upper lumbar spinal nerves. They all pass through white rami communicantes to the adjacent sympathetic trunk ganglia. Many of these preganglionic fibers synapse with the cells of the ganglia; others pass upward or downward in the sympathetic trunks to form synapses with neurons in other cervical, lumbar, and sacral ganglia. Still other preganglionic fibers pass through the sympathetic trunk ganglia without relaying and run in splanchnic nerves to end in ganglia, such as the celiac and mesenteric or the adrenal medulla. The postganglionic axons all pass to adjacent spinal nerves as gray rami communicantes; this explains why all spinal nerves have gray rami communicantes, whereas white rami communicantes are limited to the thoracolumbar region. Also shown is the recurrent meningeal sympathetic branch carrying postganglionic fibers to the spinal meninges and the spinal perivascular plexuses.

Cholinergic and Adrenergic Nerves

The terms “adrenergic” and “cholinergic,” introduced by Dale in 1933, are based on the concept that synaptic transmission between autonomic nerve fibers, and between the postganglionic axon and the structures they innervate, is effected by adrenergic or cholinergic chemicals.

Epinephrine (adrenaline), and the closely related norepinephrine (noradrenaline), are the chief neurotransmitters at peripheral sympathetic or adrenergic terminations, whereas acetylcholine is generally associated with parasympathetic, or cholinergic effects. However, in reality, acetylcholine is an important neurotransmitter at synapses in both sympathetic and parasympathetic pathways. Dale's terms were initially applied only to postganglionic fibers ; acetylcholine, in fact, is the chief neurotransmitter at synapses between preganglionic fibers and ganglionic neurons of both the sympathetic and parasympathetic systems.

The illustration shows the sites at which acetylcholine (C) and norepinephrine (A) are the chief neurotransmitters. Other chemical substances, such as adenosine triphosphate (ATP), gamma-aminobutyric acid (GABA), a polypeptide called substance P, histamine, glutamic acid, and prostaglandins have also been implicated as neurotransmitters.

Sympathetic or adrenergic efferent nerve fibers usually elicit active reactions in effector structures, such as smooth (unstriated) muscle or glands, which are the reverse of the diminished activity produced by parasympathetic, or cholinergic, fibers. Thus stimulation of the sympathetic and parasympathetic cardiac nerves produces cardiac acceleration and deceleration. However, these effects are not universal. For example, activity of the alimentary adrenergic nerves produces slowing of gastrointestinal motility; conversely, activity in the cholinergic supply results in acceleration of gastric and intestinal movements. Similar reactions occur in other structures. Thus in the urinary tract, the sympathetic nerves produce relaxation of the bladder wall, and the parasympathetic nerves cause contraction, so the former have been aptly described as “filling” and the latter as “emptying” nerves.

Sweat glands are classified as apocrine or eccrine glands. The apocrine glands open into the lumen of the sweat glands in the axilla, perineum, and periareolar region and are innervated by adrenergic fibers and probably respond to humoral epinephrine. The eccrine sweat glands open directly into the skin and are innervated by sympathetic postganglionic fibers that are cholinergic. Eccrine glands are one of the most important skin appendages and play a vital role in temperature regulation.

Autonomic Nerves in Head and Neck

The cervical part of each sympathetic trunk generally has four ganglia: superior and middle cervical, vertebral, and cervicothoracic . The superior and middle cervical ganglia are usually connected by a single cord, but the middle cervical, vertebral, and cervicothoracic ganglia are connected by several cords, one or more of which form a loop, the ansa subclavia, around the subclavian artery and sometimes also around the vertebral artery. A true inferior cervical ganglion is present only in about 20% of individuals; in the majority, the lowest cervical and uppermost thoracic ganglia are fused to form the cervicothoracic (stellate) ganglion.

The superior cervical ganglion is fusiform in shape. It is produced by the coalescence of the upper three or four cervical ganglia. The preganglionic fibers emerge through the uppermost thoracic spinal nerves and ascend to it as the cervical sympathetic trunk; a relatively small number of these fibers are from adjacent cervical nerve roots. A small proportion of the preganglionic fibers pass through it without interruption and relay at higher levels in the internal carotid ganglia.

The superior cervical ganglion receives and supplies communicating, visceral, vascular, muscular, osseous, and articular rami. It communicates with the last four cranial nerves or their branches, with the vertebral arterial plexus and, occasionally, with the phrenic nerve. It supplies gray rami to the upper three or four cervical spinal nerves, and the contained postganglionic fibers are distributed with the branches of the cervical nerves. Visceral fibers pass to the larynx, pharynx, and heart, and other fibers are carried in vascular plexuses to the salivary, lacrimal, pituitary, pineal, thyroid, and other glands. Vascular fibers are supplied to the internal and external carotid arteries and form plexuses around them; nerve continuations from these plexuses form subsidiary plexuses around all their branches. From the internal carotid plexus, minute caroticotympanic offshoots join the tympanic branch of the glossopharyngeal nerve and thus reach the tympanic plexus. A deep petrosal branch unites with the greater petrosal nerve to form the nerve of the pterygoid canal , which constitutes the sympathetic root of the pterygopalatine ganglion . The sympathetic fibers are postganglionic and run through the ganglion without relaying, to be distributed to vessels and glands in the nose, palate, nasopharynx, and orbit. The sympathetic root of the ciliary ganglion arises from the cranial end of the ipsilateral internal carotid nerves or plexus; its fibers are postganglionic, having relayed in the superior cervical or internal carotid ganglia; they pass through the ganglion and run onward in the ciliary nerves to supply the ocular vessels and the dilator pupillae. In addition to postganglionic efferent fibers, many visceral efferent and afferent fibers are also present in the vascular plexuses. They convey sympathetic efferent output to the pituitary, lacrimal, salivary, thyroid, and other smaller glands in the territories supplied by the carotid arteries, and they also transmit sensory information from the same structures. In a similar fashion, sympathetic fibers are carried to adjacent osseous, articular, and muscular structures.

The middle cervical ganglion is much smaller than the superior ganglion and usually represents fused fifth and sixth cervical ganglia. It contributes gray rami communicantes to the fifth and sixth cervical nerves and sends fibers to the vertebral periarterial plexus. Inconstant strands form interconnections with the vagus, phrenic, and recurrent laryngeal nerves, and visceral branches are supplied to the thyroid and parathyroid glands. The ganglion may give off the middle cervical sympathetic cardiac nerve and contributes several twigs to the esophagus and trachea. Vascular branches help in the innervation of the common carotid, inferior thyroid and vertebral arteries and the jugular veins. Fibers pass to adjacent muscular, osseous, and articular structures, usually alongside the arteries supplying them.

The vertebral ganglion is small and is located anterior to the vertebral artery, near its point of entry into the transverse foramen of the sixth cervical vertebra. It may receive gray rami communicantes from the sixth and/or seventh cervical nerves, and thus may represent a detached element of the middle cervical ganglion or the cervicothoracic ganglion. It gives off vascular branches that accompany the vertebral artery; it may be connected by fibers to the vagus and phrenic nerves; and it supplies tiny visceral branches to the thyroid gland, trachea, and esophagus.

The cervicothoracic (stellate) ganglion is formed by the fusion of the seventh and eighth cervical ganglia with the first and/or second thoracic ganglia. It is an irregularly fusiform structure with many radiating branches. The cervicothoracic ganglion is situated posterior to the first part of the subclavian artery, the origin of the vertebral artery, the vertebral vein, and the apex of the lung. It lies anterior to the last cervical transverse process, the neck of the first rib, and the anterior primary ramus of the eighth cervical nerve as it passes outward to unite with the corresponding ramus of the first thoracic nerve to form the inferior trunk of the brachial plexus. The vertebral vessels run over the upper pole of the ganglion, and the superior intercostal vessels run lateral to it at the level of the neck of the first rib. An aponeurotic slip from the scalene muscles spreads out to become attached to the suprapleural membrane and may veil the ganglion during the anterior operative approach. If a scalenus minimus is present, it may also obscure the ganglion.

The cervicothoracic ganglion receives white rami communicantes from the first and second thoracic nerves and sends gray rami communicantes to the eighth cervical and first thoracic nerves and, occasionally, to the seventh cervical and second thoracic nerves. These rami carry efferent and afferent sympathetic fibers to and from the brachial plexus and the uppermost intercostal nerves, thus helping to innervate vessels, sweat glands, arrectores pilorum, bones, and joints in the upper limbs and superior parts of the chest wall. The ganglion or the ansa subclavia invariably communicate with the ipsilateral phrenic nerve, and almost constantly with the vagus or the recurrent laryngeal nerve. Fibers are supplied to the heart, esophagus, trachea, and thymus. Some vascular fibers from the ganglion pass directly to the large vessels in the cervicothoracic inlet, but most of the sympathetic fibers for the upper limb structures enter the inferior trunk of the brachial plexus. They pass mainly into the medial cord of the plexus and then into the median and ulnar nerves and, to a lesser extent, into the axillary, radial, musculocutaneous, and other branches of the plexus. Vasomotor and sudomotor disturbances, or causalgia, are therefore most likely to follow irritation or injury to the inferior trunk of the brachial plexus or to the ulnar or median nerves.

Most of the preganglionic fibers for the upper limbs emerge through the anterior rami of the second to sixth or seventh thoracic nerves, and the second and third nerves probably contain the majority of the fibers.

Autonomic Innervation of Eye

The eye receives a rich innervation by the sympathetic and parasympathetic systems.

Autonomic Nerves in Thorax

The thoracic parts of the sympathetic trunks lie anterior to the junctions between the heads and necks of the ribs and posterior to the pleura. There are usually 10 or 11 ganglia on each side; the first is often incorporated into the cervicothoracic (stellate) ganglion (see Plate 7-6 ), and the last thoracic and first lumbar ganglia may also be united. The interganglionic cords are usually single, but double or triple cords between some adjacent ganglia are not uncommon. The thoracic trunks supply or receive communicating, visceral, vascular, muscular, osseous, and articular branches.

Each ganglion receives at least one white ramus communicans and contributes at least one gray ramus to the adjacent spinal nerve, although several white and gray rami communicantes may be attached to each ganglion. Visceral branches are supplied to the heart and pericardium, lungs, trachea and bronchi, esophagus, and thymus.

Sympathetic Cardiac Nerves . Three pairs of sympathetic cardiac nerves arise from the cervical trunk ganglia, and the others emerge from the upper thoracic ganglia.

The superior cervical sympathetic cardiac nerves originate from the corresponding trunk ganglia. On the right, the nerve passes posterolateral to the brachiocephalic artery and aortic arch; on the left, it curves downward over the left side of the aortic arch to reach the cardiac plexus.

The middle cervical sympathetic cardiac nerves are usually larger than the corresponding superior and inferior nerves. They arise from the middle cervical and vertebral ganglia of the sympathetic trunks and usually run independently to the cardiac plexus.

The inferior cervical sympathetic cardiac nerves consist of fibers arising from the cervicothoracic ganglia and subclavian ansae.

The thoracic sympathetic cardiac nerves are four or five slender branches, which run forward and medially from the thoracic trunk ganglia to the cardiac plexus.

Parasympathetic Cardiac Nerves . Three pairs of parasympathetic (vagal) cardiac nerves are usually present. The superior cervical vagal cardiac branches leave the vagus nerves in the upper part of the neck. The inferior cervical vagal cardiac branches arise in the lower third of the neck and descend posterolateral to the brachiocephalic artery and aortic arch on the right side; on the left side, they descend lateral to the left common carotid artery and aortic arch. The thoracic vagal cardiac branches arise at or below the level of the thoracic inlet.

Multiple interconnections exist between all the sympathetic and parasympathetic cardiac nerves and between the cardiac and other visceral branches of the sympathetic trunks.

Other thoracic sympathetic branches supply the thoracic viscera from the paired greater, lesser, and lowest thoracic splanchnic nerves, although these are mainly destined to supply abdominal structures and contain a mixture of preganglionic, postganglionic, and afferent fibers. The greater (major) splanchnic nerve lies medial to the ipsilateral sympathetic trunk and enters the abdomen by piercing the crus of the diaphragm. The lesser (minor) splanchnic nerve lies slightly lateral to the greater splanchnic nerve and also usually pierces the diaphragmatic crus. The lowest (imus) splanchnic nerve is inconstant.

Minute twigs from the sympathetic trunks join and innervate the intercostal arteries. Other sympathetic postganglionic fibers reach these vessels in fascicles from adjacent intercostal nerves or their branches, and these also carry sudomotor and pilomotor fibers.

The muscular, osseous, and articular fibers from the thoracic sympathetic trunks and their branches supply the adjacent structures concerned; their exact functions are uncertain.

Innervation of Blood Vessels

Blood vessels are innervated by afferent and efferent autonomic nerves. All receive sympathetic fibers, but some may not have a parasympathetic supply. The great vessels near the midline in the neck and body cavities receive direct innervation from adjacent parts of the sympathetic trunks. Some of these vessels and their branches also obtain supplies from nearby autonomic plexuses, which contain both sympathetic and parasympathetic elements. Thus the ascending aorta, the aortic arch and its branches, and the superior vena cava receive offshoots from the cardiac plexus; the pulmonary vessels, from the pulmonary plexuses; the celiac, hepatic, gastric, splenic, superior mesenteric, renal, and adrenal vessels and the portal and inferior caval veins, from the celiac and superior mesenteric plexuses; the inferior mesenteric vessels, from the corresponding plexus; and the pelvic vessels, from the superior and inferior hypogastric plexuses.

The chief outflow of sympathetic preganglionic fibers is through the anterior roots of spinal nerves T1 to L2. The fibers pass in white rami communicantes to adjacent sympathetic trunk ganglia, where many relay. The axons of these ganglionic cells (postganglionic fibers) may pass in nerves to nearby structures, such as midline vessels and prevertebral plexuses (cardiac, celiac, mesenteric), or they may join the lowest cervical, thoracic, and upper lumbar spinal nerves through gray rami communicantes, to be distributed with them to vessels and glands in the thoracic and abdominal cavities and limbs.

Other preganglionic fibers, however, do not relay in adjacent trunk ganglia, but ascend or descend in the sympathetic trunks to form synapses in the cervical or lower lumbar and sacral ganglia. The axons (postganglionic fibers) of the cervical ganglionic cells supply the vessels and glands in the head and neck, while others contribute to the sympathetic cervical cardiac nerves. Some of the postganglionic fibers arising in the lumbar and sacral ganglia run in lumbar and sacral splanchnic nerves to the mesenteric and hypogastric plexuses, but others pass through gray rami communicantes to the lumbar, sacral, and coccygeal spinal nerves to be distributed with them and their branches to vessels, sweat glands, and arrectores pilorum muscles in the loin, lower abdominal wall, buttocks, perineum, and lower limbs.

The vascular nerves from the diverse sources unite around individual vessels in wide-meshed perivascular adventitial plexuses . Fascicles arising from these sink inward to form more delicate plexuses between the adventitial and medial coats, from which nerve fibers originate to ramify in the media and in the zone between the media and intima. Subsidiary perivascular plexuses extend along the vessel branches and are augmented at intervals by branchlets from nearby cranial or spinal nerves, which contain autonomic fibers. Thus innervation is segmental rather than longitudinal, and only relatively short lengths of arteries can be denervated by the removal of adventitial cuffs.

Most cranial and spinal nerves contain efferent and afferent vascular fibers. The oculomotor (III), trigeminal (V), facial (VII), vagus (X), glossopharyngeal (XI), phrenic, ulnar, median, pudendal, and tibial nerves contain relatively large numbers of vascular fibers. Accordingly, lesions involving these nerves are more likely to produce vasomotor and other autonomic disturbances. Vascular disorders are usually more evident in peripheral arteries and arterioles (like those in the fingers and toes) and in arteriovenous anastomoses because they have thicker muscular layers and a richer innervation than larger arteries, which have more elastic tissue in their walls. Arteries supplying erectile tissues and the skin are also richly innervated, whereas the nerve supply to veins and venules is comparatively sparse. Nerve fibers are often associated with capillaries, but their functions are unknown.

Carotid Sinus and Carotid Body. The carotid sinus is a dilation in at the beginning of the internal carotid artery; the tunica media is thin, and adventia are thicker with multiple terminations of the glossopharyngeal nerve. The carotid sinus serves as a baroreceptor and plays an important role in the control of intracranial blood pressure. The carotid body is a small reddish brown structure behind the bifurcation of the common carotid artery and is a chemoreceptor.