13 Autonomic nervous system and visceral afferents

1 Resolve the paradox that despite an outflow restricted to 14 or 15 ventral roots, all 31 spinal nerve trunks acquire sympathetic fibers.

2 Appreciate that the sympathetic ganglia along the abdominal aorta are activated by preganglionic fibers, as is the adrenal medulla.

3 Pay special attention to the autonomic innervation of the eye, both here and in Chapter 23.

4 Appreciate that the four parasympathetic ganglia in the head are functionally similar to intramural ganglia elsewhere.

5 The pelvic ganglia are mixed autonomic ganglia.

6 Realize that the preganglionic neurons of both divisions are cholinergic and that the target receptors in all of the autonomic ganglia are nicotinic.

7 Note that at tissue level, synapses are replaced by looser ‘junctions’ which permit diffusion of transmitter to outlying receptors.

8 You should focus on four kinds of junctional receptors of the sympathetic system, and on four actions initiated by muscarinic receptors in the parasympathetic system.

9 Learn from Clinical Panel 13.2 how pharmacologists intercept the recycling and degradation sequence at sympathetic nerve endings. The same principles apply to CNS drug therapy, notably in psychiatric disorders.

10 Follow Clinical Panel 13.3 to contrast the effects of cholinergic and anticholinergic drugs.

11 Visceral afferents utilize autonomic pathways to gain access to the nervous system. They are especially important in the context of thoracic and abdominal pain.

Components of the Autonomic Nervous System

The autonomic (‘self-regulating’) nervous system is distributed to the peripheral tissues and organs by way of outlying autonomic ganglia. Controlling centers in the hypothalamus and brainstem send central autonomic fibers to synapse upon preganglionic neurons located in the gray matter of the brainstem and spinal cord. From these neurons, preganglionic fibers (mostly myelinated) project out of the CNS to synapse upon multipolar neurons in the autonomic ganglia. Unmyelinated postganglionic fibers emerge and form terminal networks in the target tissues.

Both anatomically and functionally, the autonomic system is composed of sympathetic and parasympathetic divisions.

Sympathetic Nervous System

The sympathetic system is so called because it acts in sympathy with the emotions. In association with rage or fear, the sympathetic system prepares the body for ‘fight or flight’: the heart rate is increased, the pupils dilate, and the skin sweats. Blood is diverted from the skin and intestinal tract to the skeletal muscles, and the sphincters of the alimentary and urinary tracts are closed.

The sympathetic outflow from the nervous system is thoracolumbar, the preganglionic neurons being located in the lateral gray horn of the spinal cord at thoracic and upper two (or three) lumbar segmental levels. From these neurons, preganglionic fibers emerge in the corresponding anterior nerve roots and enter the paravertebral sympathetic chain. The fibers do one of four things (Figure 13.1):

1 Some fibers synapse in the nearest ganglion. Postganglionic fibers enter spinal nerves T1–L2 and supply blood vessels, sweat glands and erector pili (hair-raising) muscles in the territory of these nerves.

2 Some fibers ascend the sympathetic chain and synapse in the superior or middle cervical ganglion, or in the stellate ganglion. (The stellate consists of the fused inferior cervical and first thoracic ganglia; it lies in front of the neck of the first rib.) Postganglionic fibers supply the head, neck, and upper limbs; also the heart. Of particular importance is the supply to the dilator muscle of the pupil (Clinical Panel 13.1).

3 Some fibers descend to synapse in lumbar or sacral ganglia of the sympathetic chain. Postganglionic fibers enter the lumbosacral plexus for distribution to the blood vessels and skin of the lower limbs.

4 Some fibers traverse the chain and emerge as the (preganglionic) thoracic and lumbar splanchnic nerves. The thoracic splanchnic nerves (usually called, simply, the splanchnic nerves) pass through the lower eight thoracic ganglia, pierce the diaphragm, and synapse within the abdomen in the celiac and mesenteric prevertebral ganglia, and in renal ganglia. Postganglionic fibers accompany branches of the aorta to reach the gastrointestinal tract, liver, pancreas, and kidneys. Lumbar splanchnic nerves pass through the upper three lumbar ganglia and meet in front of the bifurcation of the abdominal aorta. They enter the pelvis as the hypogastric nerves before ending in pelvic ganglia, from which the genitourinary tract is supplied.

Figure 13.1 General plan of the sympathetic system. Ganglionic neurons and postganglionic fibers are shown in red. LG, lumbar ganglia; LSN, lumbar splanchnic nerve; MCG, middle cervical ganglion; SCG, superior cervical ganglion; SG, sacral ganglia; StG, stellate ganglion; TG, thoracic ganglia; TSN, thoracic splanchnic nerve.

Clinical Panel 13.1 Sympathetic interruption

Stellate block

Injection of local anesthetic around the stellate ganglion – stellate block – is a procedure used in order to test the effects of sympathetic interruption on blood flow to the hand. Both pre- and postganglionic fibers are inactivated, producing sympathetic paralysis in the head and neck on that side, as well as in the upper limb. A successful stellate block is demonstrated by (a) a warm, dry hand, (b) Horner’s syndrome, which consists of a constricted pupil owing to unopposed action of the pupillary constrictor, and (c) ptosis (drooping) of the upper eyelid owing to paralysis of smooth muscle fibers contained in the levator muscle of the upper eyelid (Figure CP 13.1.1).

Dominance of the right stellate ganglion in control of the heart rate is shown by the marked slowing of the pulse following a right, but not a left, stellate block. (See also Box 13.1.)

Functional sympathectomy of the upper limb may be carried out by cutting the sympathetic chain below the stellate ganglion. This is not an anatomical sympathectomy because the ganglionic supply to the limb from the middle cervical and stellate ganglia remains intact. It is a functional one because the ganglionic neurons for the limb are deprived of tonic sympathetic drive. Horner’s syndrome is avoided by making the cut at the level of the second rib: the preganglionic fibers for the head and neck enter the stellate direct from the first thoracic spinal nerve.

Two indications for interruption of the sympathetic supply to one or both upper limbs are painful blanching of the fingers in cold weather (Raynaud phenomenon), and hyperhidrosis (excessive sweating) of the hands – usually an embarrassing affliction of teenage girls.

The sympathetic supply to the eye is considered further in Chapter 23.

Lumbar sympathectomy

In order to improve blood flow in the lower limb, the preganglionic nerve supply may be interrupted by cutting the upper end of the lumbar sympathetic chain. The usual procedure is to remove the second and third lumbar sympathetic ganglia. In males, bilateral lumbar sympathectomy may result in persistent, painful erections (priapism) because of interruption of a pathway that maintains the resting, flaccid state of the penis.

Figure CP 13.1.1 Horner’s syndrome, patient’s right side. Note the moderate ptosis of the eyelid, and the moderate miosis (pupillary constriction). The affected pupil reacts to light but recovers very slowly.

The medulla of the adrenal gland is the homolog of a sympathetic ganglion, being derived from the neural crest. It receives a direct input from fibers of the thoracic splanchnic nerve of its own side (see later).

The sympathetic system exerts tonic (continuous) constrictor activity on blood vessels in the limbs. In order to improve the blood flow to the hands or feet, impulse traffic along the sympathetic system can be interrupted surgically (Clinical Panel 13.1).

Parasympathetic Nervous System

The parasympathetic system generally has the effect of counterbalancing the sympathetic system. It adapts the eyes for close-up viewing, slows the heart, promotes secretion of salivary and intestinal juices, and accelerates intestinal peristalsis. A notable instance of concerted sympathetic and parasympathetic activity occurs during sexual intercourse (Box 13.4).

The parasympathetic outflow from the CNS is craniosacral (Figure 13.2). Preganglionic fibers emerge from the brainstem in four cranial nerves – the oculomotor, facial, glossopharyngeal, and vagus – and from sacral segments of the spinal cord.

Figure 13.2 General plan of the parasympathetic system. Ganglionic neurons and postganglionic fibers are shown in red. CG, ciliary ganglion; HG, heart ganglia; IG, intramural ganglia; MG, myenteric ganglia; OG, otic ganglion; PtG, pterygopalatine ganglion; SG, submandibular ganglion.

Cranial parasympathetic system

Preganglionic parasympathetic fibers emerge in four cranial nerves (Figure 13.3):

1 In the oculomotor nerve, to synapse in the ciliary ganglion. Postganglionic fibers innervate the sphincter of the pupil and the ciliary muscle. Both muscles act to produce the accommodation reflex.

2 In the facial nerve, to synapse in the pterygopalatine ganglion, which innervates the lacrimal and nasal glands; and in the submandibular ganglion, which innervates the submandibular and sublingual glands.

3 In the glossopharyngeal nerve, to synapse in the otic ganglion, which innervates the parotid gland.

4 In the vagus nerve, to synapse in mural (‘on the wall’) or intramural (‘in the wall’) ganglia of heart, lungs, lower esophagus, stomach, pancreas, gall bladder, small intestine, and ascending and transverse parts of the colon.

Figure 13.3 Cranial parasympathetic system. E–W, Edinger–Westphal nucleus; DNX, dorsal nucleus of vagus. Other abbreviations as in Figure 13.2.

Sacral parasympathetic system

The sacral segments of the spinal cord occupy the conus medullaris (conus terminalis) at the lower extremity of the spinal cord, behind the body of the first lumbar vertebra. From the lateral gray matter of segments S2, S3 and S4, preganglionic fibers descend in the cauda equina within ventral nerve roots. Upon emerging from the pelvic sacral foramina, the fibers separate out as the pelvic splanchnic nerves. Some fibers of the left and right pelvic splanchnic nerves synapse on ganglion cells in the wall of the distal colon and rectum. The rest synapse in pelvic ganglia, close to the pelvic sympathetic ganglia already mentioned. Postganglionic parasympathetic fibers supply the detrusor muscle of the bladder; also the tunica media of the internal pudendal artery and of its branches to the cavernous tissue of the penis/clitoris (see later).

Neurotransmission in the Autonomic System

Ganglionic transmission

The preganglionic neurons of the sympathetic and parasympathetic systems are cholinergic: the neurons liberate acetylcholine (ACh) on to the ganglion cells at axodendritic synapses (Figure 13.4). The receptors on the ganglion cells are nicotinic, so named because the excitatory effect can be imitated by locally applied nicotine.

Figure 13.4 Autonomic transmitters and receptors. Ganglionic neurons and postganglionic fibers are shown in red. ACh, acetylcholine; M, muscarinic receptors; N, nicotinic receptors; NE, norepinephrine.

Junctional transmission

Postganglionic fibers of the sympathetic and parasympathetic systems form neuroeffector junctions with target tissues (Figure 13.4). Transmitter substances are liberated from innumerable varicosities strung along the course of the nerve fibers.

The chief transmitter at sympathetic neuroeffector junctions is norepinephrine (noradrenaline), which is liberated from dense-cored vesicles. The postganglionic sympathetic system in general is described as adrenergic. An exception to the adrenergic rule is the cholinergic sympathetic supply to the eccrine sweat glands over the body surface.

The chief transmitter at parasympathetic neuroeffector junctions is ACh. The postganglionic parasympathetic system in general is cholinergic.

Junctional receptors

The physiological effects of autonomic stimulation depend upon the nature of the postjunctional receptors inserted by target cells into their own plasma membranes. In addition, transmitter release is influenced by prejunctional receptors in the axolemmal membrane of the nerve terminals.

Sympathetic junctional receptors (adrenoceptors) (Figure 13.5)

Two kinds of α adrenoceptor and two kinds of β adrenoceptor have been identified for norepinephrine:

1 Postjunctional α₁ adrenoceptors initiate contraction of smooth muscle in peripheral small arteries and large arterioles; the dilator pupillae; the sphincters of the alimentary tract and bladder neck; and the vas deferens.

2 Prejunctional α₂ adrenoceptors are present on parasympathetic as well as on sympathetic terminals. They inhibit transmitter release in both cases. On sympathetic terminals, they are called autoreceptors.

3 Postjunctional β₁ adrenoceptors increase pacemaker activity in the heart and increase the force of ventricular contraction (Box 13.1). In response to a severe fall of blood pressure, sympathetic activation of β₁ receptors on the juxtaglomerular cells of the kidney causes secretion of renin. Renin initiates production of the powerful vasoconstrictor angiotensin II.

4 β₂ receptors respond to circulating epinephrine (adrenaline) (Figure 13.6) in addition to locally released norepinephrine.