Autonomic nervous system

The autonomic nervous system (ANS) is part of the peripheral nervous system and regulates involuntary, visceral body functions in different organ systems (e.g., the cardiovascular, gastrointestinal, genitourinary systems). It is divided into the sympathetic and parasympathetic nervous systems. The sympathetic nervous system has a thoracolumbar outflow and is activated during fight or flight response, while the parasympathetic nervous system has a craniosacral outflow and is activated during digestion and rest. The sympathetic and parasympathetic nervous systems consist of preganglionic and postganglionic neurons. The preganglionic fibers of both ANS divisions and the postganglionic fibers of the parasympathetic division are cholinergic fibers (release acetylcholine) that act on cholinergic receptors (nicotinic or muscarinic). All postganglionic fibers of the sympathetic division are adrenergic fibers (release norepinephrine) that act on adrenergic alpha or beta receptors for neurotransmission, with the exception of the fibers innervating the sweat glands, which are cholinergic. The adrenal medulla does not have a postsynaptic neuron. The sympathetic preganglionic fibers stimulate the chromaffin cells of the adrenal medulla directly via acetylcholine on nicotinic receptors, which results in the release of norepinephrine and epinephrine mediating the fight or flight response. The sympathetic and parasympathetic nervous systems have antagonistic effects in some organ systems. The effects of the sympathetic nervous system on target organs include mydriasis, increased heart rate, contractility, and conduction velocity, bronchodilation, sweat secretion, decreased intestinal motility, and increased renin release. The effect of the parasympathetic nervous system on target organs include miosis, decreased heart rate, contractility, and conduction velocity; increased intestinal motility; and bronchoconstriction. In addition to the sympathetic and parasympathetic nervous systems, there is the enteric nervous system, which consists of enteric ganglia, the myenteric (Auerbach) and the submucosal (Meissner) plexuses, and the interstitial cells of Cajal. The enteric nervous system controls gastrointestinal motility and secretion. Autonomic function can be affected by medications (e.g., selective serotonin reuptake inhibitors, anticholinergics) as well as diseases (e.g., diabetes mellitus, Parkinson disease, multiple system atrophy).

• Function: controls unconscious, involuntary, and visceral body functions, i.e., the cardiovascular, thermoregulatory, gastrointestinal, genitourinary, and pupillary systems
• Components
  • Visceral motor (efferent) pathways: made up of preganglionic neurons (originate in brain or spinal cord) and postganglionic neurons (cell body in autonomic ganglion outside the CNS)
    • Sympathetic
    • Parasympathetic
  • Visceral sensory (afferent) pathways: originate in visceral receptors that are sensitive to physiological stimuli (e.g., mechanical, thermal)
  • Ganglia (neuroanatomy): in neuroanatomy, a ganglion is an accumulation of neuron cell bodies outside the CNS
  • Nuclei (neuroanatomy): in neuroanatomy, a nucleus is an accumulation of neuron cell bodies in the CNS
  • Enteric nervous system

Types of receptors

• See “Signal transduction.”

All beta receptors are coupled with G_s proteins. Odd alpha receptors and muscarinic acetylcholine receptors (alpha-1, M1, M3, and M5) are coupled with G_q proteins. Even alpha receptors and muscarinic acetylcholine receptors (alpha-2, M2, and M4) are coupled with G_i proteins.

Types of nerve fibers

• Small myelinated fibers: transmit preganglionic autonomic efferents and somatic afferents (fast)
• Unmyelinated fibers (e.g., which innervate sweat glands): transmit postganglionic autonomic efferents and somatic/autonomic afferents (slow)

Neurotransmitters

• Acetylcholine
  • All preganglionic fibers
  • All parasympathetic postganglionic fibers
  • Sympathetic postganglionic fibers for sweat glands and arrector pili muscles
• Norepinephrine
  • All sympathetic postganglionic fibers
  • Exceptions: sweat glands and arrector pili muscles (acetylcholine), adrenal medulla (80% epinephrine, 20% norepinephrine), renal arteries (dopamine)

Transmitters of the sympathetic nervous system are acetylcholine (preganglionic → postganglionic neurons) and norepinephrine (postganglionic neurons → effector organ).

ANS innervation of organs

For a rapid overview see table “Overview of the sympathetic and parasympathetic nervous system.” ^[1]

Sympathetic nervous system

• Structure
  • Descends from central nervous system to T1–L2 (thoracolumbar outflow)
  • Neuron cell bodies are located in the lateral horn of the spinal cord.
• Preganglionic axons (short myelinated, cholinergic fibers) exit the spinal cord through ventral roots, spinal nerves, and white rami communicantes. They either:
  • Connect to paravertebral ganglia, which lie near the vertebral column and synapse with postsynaptic cells at the same level
  • Travel up or down the chain of paravertebral ganglia to synapse in a more superior or inferior paravertebral ganglion with a postsynaptic cell
  • Run through paravertebral ganglia without synapsing and further through the splanchnic nerves to synapse in the prevertebral ganglia (innervate pelvic viscera), which are located in front of the vertebral column, around the origins of the major branches of the abdominal aorta
  • Or pass through paravertebral and prevertebral ganglia and directly synapse on chromaffin cells of the adrenal medulla.
• Postganglionic axons: (long unmyelinated, mostly adrenergic fibers): leave the paravertebral or prevertebral ganglia and innervate end organs

Sympathetic ganglia

Paravertebral ganglia

• Structure: form a chain of ganglia on each side of the vertebral column running from the base of the skull to the coccyx, which forms the sympathetic trunk
• Include: superior cervical, middle cervical, and cervicothoracic (stellate) ganglia ., the thoracic (12), lumbar (4), and sacral (4) ganglia, and the ganglion impar (unpaired)
• Function
  • All paravertebral ganglia: innervation of blood vessels, arrector pili muscles, and sweat glands
  • Superior cervical ganglion: innervates sublingual gland, submandibular gland, parotid gland, carotid body, choroid plexus, dilator pupillae, and levator palpebrae superioris
  • Middle cervical ganglion: branches to thyroid gland, supplies heart
  • Stellate ganglion: supplies head, neck, arms, heart, and lungs
  • Thoracic sympathetic ganglia
    • Upper thoracic sympathetic trunk: forms the cardiac plexus, pulmonary plexus, aortic plexus, and esophageal plexus, which supply the neck, upper limbs, and thorax (i.e., heart, aorta, trachea, lungs, and esophagus)
    • Lower thoracic sympathetic trunk (T5–T12): mainly gives preganglionic fibers that form the splanchnic nerves, which go to the celiac and aorticorenal ganglion and supply the abdominal viscera
  • Lumbar and sacral sympathetic ganglia: innervate the pelvic floor and lower limbs

Prevertebral ganglia (or preaortic ganglia)

• Not part of the sympathetic trunk
• Closely associated with the major abdominal branches of the aorta:
  • Celiac ganglion near the origin of the celiac artery: innervates the liver (via hepatic plexus), gallbladder, bile duct, spleen (via splenic plexus), pancreas, adrenal glands (via suprarenal plexus), and the first part of the small intestine
  • Aorticorenal ganglion (detached part of lower celiac ganglion) close to the the renal artery: forms renal plexus and innervates the kidneys
  • Superior mesenteric ganglion near the origin of the superior mesenteric artery: innervates the small intestine
  • Inferior mesenteric ganglion near the origin of the inferior mesenteric artery: innervates the descending colon, sigmoid colon, rectum, urinary bladder, and sexual organs

Injury to the cervical sympathetic trunk (esp. the superior cervical ganglion, which supplies the visceral structures of the head and neck) may result in Horner syndrome (partial ptosis, miosis, anhidrosis).

For a rapid overview see table “Overview of the sympathetic and parasympathetic nervous system.”

General information

• Exits central nervous system (dorsal motor nucleus) with cranial nerves CN III, CN VII, CN IX, CN X, and the sacral spinal roots (craniosacral outflow)
• Preganglionic axons; (long, myelinated cholinergic fibers): synapse in ganglia close to end organs
• Postganglionic axons; (short, cholinergic fibers): leave ganglia and innervate end organs

Cranial outflow

The cranial outflow supplies visceral structures of the head, neck and face via CN III, CN VII, CN IX and of the thorax and upper abdomen via CN X.

• Four bilateral autonomic ganglia in the head and neck:
  • Edinger-Westphal nucleus → oculomotor nerve (CN III) → ciliary ganglion → sphincter pupillae (miosis) and ciliary muscle (accommodation)
  • Superior salivatory nucleus → facial nerve → pterygopalatine ganglion and submandibular ganglion → lacrimal gland, glands of the mucosa of the oral and nasal cavity, pharynx, and sinuses
  • Inferior salivatory nucleus → glossopharyngeal nerve → otic ganglion → salivation of parotid gland
• Dorsal nucleus of the vagus nerve → CN X → several ganglia close to/or within the walls of the gastrointestinal tract and lungs

Sacral outflow

• Supplies pelvis via 2^nd–4^th sacral spinal nerves
• Lateral horn of the sacral segments of S2–S4 → pelvic splanchnic nerves → inferior hypogastric plexus or ganglia within walls of pelvic (e.g., descending and sigmoid colon, rectum, ureter, prostate, bladder, urethra) and genital organs.

The sympathetic and parasympathetic nervous systems mediate numerous, sometimes antagonistic effects in the organs they innervate. In general, the sympathetic nervous system stimulates the body’s fight-or-flight response, while the parasympathetic nervous system controls homeostasis and the body at rest.

The sympathetic nervous system is for fight or flight. The parasympathetic nervous system is for rest and digest.

The enteric nervous system has complex networks of afferent and efferent nerve fibers. It can operate independently of the brain and the spinal cord but its activity is usually modulated by the sympathetic and parasympathetic nervous systems.

• Consists of:
  • Enteric ganglia
  • Plexuses of the GI tract (enteric ganglia)
    • Submucosal plexus (Meissner plexus)
    • Myenteric plexus (Auerbach plexus)
  • Interstitial cells of Cajal (ICCs)
    • Located in the wall of the intestine
    • Act as pacemaker cells for peristaltic motor activity of the gut
    • Connected to smooth muscle cells via gap junctions
    • Generate spontaneous electrical slow waves and thus rhythmic contractions of the smooth musculature (i.e., peristalsis)
• Function: control of GI secretion and motility

Plexuses

• Location: found within the intestinal wall, beginning in the esophagus and extending down to the anus
  • Submucous plexus (Meissner plexus): found in submucosa
  • Myenteric plexus (Auerbach plexus): found in muscularis propria (plexus is located between circular and longitudinal muscle layers)
• Structure
  • Efferent neurons, afferent neurons, and interneurons
  • Derived from neural crest cells
  • Transmitter: e.g., acetylcholine, dopamine, and serotonin
• Function
  • Promote GI secretions for digestion
  • Allow sphincter relaxation for food to pass
  • Stimulate GI peristalsis
• Input
  • Sympathetic
    • Prevertebral ganglia: celiac, superior mesenteric, and inferior mesenteric ganglia
    • Splanchnic, hypogastric, and colonic nerves
  • Parasympathetic
    • Vagus nerve
    • Sacral outflow S2–S4
• Effect of input
  • Sympathetic fibers: ↓ GI peristalsis and secretion, constriction of GI sphincters
  • Parasympathetic fibers: ↑ GI peristalsis and secretion, relaxation of GI sphincters

Whereas the sympathetic system has an inhibitory effect on the gastrointestinal tract, the parasympathetic system promotes secretion and motility. However, removal of vagal or sympathetic connections with the gastrointestinal tract only has a minor effect on GI function because of the autonomy of the enteric nervous system.

• Autonomic dysfunction
  • Can be caused by neurologic disease, metabolic disorders (e.g., Wilson disease), age-related changes, or effects of pharmacotherapy
  • May present with any combination of dysfunction of autonomically-regulated processes (e.g., urination, defecation, sweating, salivation, blood pressure regulation, heart rate)
• Multiple system atrophy
• Diabetes mellitus
• Multiple sclerosis
• Medication-induced autonomic dysfunction
• Guillain-Barré syndrome
• Lyme disease
• Achalasia
• GIST
• Sympathetic denervation
• Horner syndrome
• Hirschsprung disease
• Parasympathomimetic drug
• Parasympatholytic drugs
• Sympathomimetic drugs
• Sympatholytic drugs