Parasympathetic Nervous System Case File

Parasympathetic Nervous System Case File

EUGENE C.TOY, MD, RAHUL JANDIAL, MD, PhD, EVAN YALE SNYDER, MD, PhD, MARTIN T. PAUKERT, MD

CASE 32

A 21-year-old previously healthy male presents to the emergency department with right-sided eye pain for the past 2 days. He has never experienced this symptom before. He states that he was watching his favorite movie when he noticed that colors seen by his right eye seemed faded and less intense than that in his left eye. Around this time he also developed worsening right eye pain. Upon further questioning, he states that he has had episodes of worsening urinary incontinence for the past month. He was embarrassed about this so he did not seek medical attention. He describes a strong urge to urinate but has difficulty initiating a stream. However, he adds that he often experiences urinary discharge when he senses no urgency at all. His cousin and sister both suffer from systemic lupus erythematosus. Eventually he is diagnosed with multiple sclerosis (MS).

• Why is he incontinent of urine?
• What function does myelin serve?
• What cells are responsible for myelination in the central nervous system (CNS)?

ANSWERS TO CASE 32: PARASYMPATHETIC NERVOUS SYSTEM

Summary: A 21-year-old male has urinary incontinence for the past month and eye pain with decreased vision and color acuity.

• Mechanism of Incontinence: Compromise of the parasympathetic tone to the detrusor muscle and external urethral sphincter resulting in urinary incontinence secondary to an MS plaque.
• Myelin: Myelin serves to protect and insulate axons, increasing conduction velocity along them.
• Myelinating cells in CNS: Oligodendrocytes myelinate axons in the CNS. Schwann cells serve the same purpose in the peripheral nervous system.

CLINICAL CORRELATION

MS is a demyelinating disease that can affect both the brain and spinal cord. Traditionally, this autoimmune disorder affects patients in their twenties, females greater than males. Twenty-five percent of patients will manifest MS as optic neuritis. In this disease there is often orbital pain worsened with eye movement, monocular vision loss, decreased color acuity, and a decreased afferent papillary response in the affected eye. For the purposes of this discussion, we will focus on the bladder dysfunction. The bladder is composed of three muscle groups: the detrusor muscle, the internal urethral sphincter, and the external urethral sphincter. The internal sphincter is smooth muscle and receives innervation from the lower thoracic interomediolateral segments. The preganglionic sympathetic fibers traverse into the posterior abdominal cavity where they synapse in the inferior mesenteric ganglion. Postganglionic sympathetic fibers innervate the smooth muscle composing the internal urethral sphincter, causing contraction and urinary retention. The external urethral sphincter is striated muscle and is under voluntary control. Cell bodies in the anterolateral horns of S2, S3, and S4 (nucleus of Onuf) send their axons along the inferior pudendal nerve to terminate onto the external sphincter, causing contraction. The detrusor muscle itself is innervated by both the sympathetic and parasympathetic nervous systems. Sympathetic fibers travel along the same pathways as the sympathetic fibers that terminate on the internal sphincter. When they terminate on the detrusor, they cause relaxation. Preganglionic parasympathetic fibers course through the inferior mesenteric ganglion and terminate onto postganglionic parasympathetic cell bodies located on the bladder wall. Firing of the postganglionic parasympathetic fibers causes detrusor contraction. There is a cerebral micturition center located on the medial frontal cortex inferior to the accessory motor cortex. This structure is responsible for conscious continence management. There is a local reflex arc that stimulates bladder emptying based on afferent sensory impulses from the detrusor muscle. However, the micturition center projects fibers onto both Onuf nucleus and the cell bodies of parasympathetic preganglionic neurons to inhibit their firing. The sequence of micturition is as follows: voluntary relaxation of the perineum, flexion of abdominal wall muscles, detrusor contraction, opening of the internal and then external sphincters. In the case of MS, these changes take place over time. The most common bladder manifestation is a neurogenic bladder resulting in spinal cord white matter lesions above T12. This results in a spastic bladder and loss of voluntary control of the external sphincter. A spastic bladder initiates an emptying reflex at lower bladder volumes and is analogous to muscle spasticity and hyper-reflexivity seen in upper motor neuron disease. This combination leads to urgency (depending on the degree of sensation that is still intact) and incontinence.

APPROACH TO PARASYMPATHETIC NERVOUS SYSTEM

Objectives

1. Understand the anatomy of the parasympathetic nervous system (see Figure 32-1).
2. Know the neurotransmitters used by the parasympathetic nervous system at the different synapses.
3. Be able to discuss the effects of the parasympathetic stimulation of major end organs.

Definitions

Craniosacral: Naming schema denoting the regions of preganglionic parasympathetic nuclei. The head distal to the splenic flexure is supplied by the brainstem nuclei while the descending colon and pelvic organs are supplied by the sacral component.

Nicotinic: The type of receptor found as autonomic preganglionic/ postganglionic synapses as well as the receptor found at neuromuscular junctions.

Muscarinic: The receptor type found at postganglionic parasympathetic/ end organ synapses.

DISCUSSION

The parasympathetic nervous system, which controls the “rest and digest” functions, is one of the two subdivisions of the autonomic nervous system. Together, these subdivisions govern the activity of cardiac muscle, smooth muscle, and glands. The autonomic nervous system is regulated by combined

efforts from the hypothalamus, cerebral cortex, amygdala, and reticular formation. As with many other portions of the nervous system, it is often easier to facilitate an anatomical discussion by dividing the pertinent pathways and projections into their central and peripheral components.

Figure 32-1. The parasympathetic (craniosacral) division of the autonomic nervous system is noted on the right. (With permission from Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. 4th ed. New York, NY: McGraw-Hill; 2000:964.)

The central organization of the parasympathetic nervous system is best understood by focusing on the hypothalamus. At this level both afferent and efferent information is processed and the tone of the parasympathetic nervous system adjusted. Afferent visceral information about blood pressure, respiratory drive, and gastrointestinal status are carried by the glossopharyngeal and vagus nerves to the solitary tract nucleus in the brainstem. This nucleus accepts and redirects nerve impulses to various areas of the brain including the hypothalamus, insular cortex, amygdala, and adjacent respiratory centers in the medulla and pons. The insular cortex is involved with cardiac function.

The highest levels of parasympathetic control and largely efferent output are achieved in the prefrontal, cingulate, and hippocampal cortices. These areas both receive and project to other regions to achieve a maximal attenuation of parasympathetic drive. By projecting to the hypothalamus, these cortical areas are able to manifest their output by altering the tone of the parasympathetic nervous system. Most parasympathetic fibers originate in the anterior regions of the hypothalamus. From here they descend into the midbrain, pons and medulla, and down the spinal cord. These axons terminate in the interomediolateral cell column of the spinal cord from S2-S4. Because the parasympathetic nervous system is confined to these two regions of termination, it often carries the designation of craniosacral.

The brainstem nuclei that distribute preganglionic parasympathetic outflow include the Edinger-Westphal nucleus of the oculomotor nerve, the superior salivatory nucleus that contributes to the facial nerve, the inferior salivatory nucleus that contributes to the glossopharyngeal nerve, and the dorsal motor nucleus of the vagal nerve. Together, these four cranial nerves carry all preganglionic parasympathetic tone to the glands and blood vessels of the head (see Figure 32-1). The Edinger-Westphal nucleus projects preganglionic parasympathetic axons along the periphery of the oculomotor nerve as it exits the midbrain and enters the orbit through the superior orbital fissure. Here the preganglionic parasympathetic fibers travel along the inferior division of the oculomotor nerve and then branch off toward the ciliary ganglion. Here they terminate and postganglionic parasympathetic fibers innervate the sphincter muscle of the pupil and ciliary muscles allowing for miosis and convergence, respectively. The superior salivatory nucleus projects preganglionic parasympathetic fibers along the facial nerve as it exits the brainstem along the pontomedullary junction. These fibers branch off the facial nerve within the greater petrosal nerve just distal to the geniculate ganglion. These fibers reenter the cranium through the hiatus for the greater petrosal nerve and run anteriorly along the skull base. They exit the skull and travel to the pterygopalatine fossa where they terminate in the pterygopalatine ganglion. Here postganglionic parasympathetic fibers travel superiorly through the inferior orbital fissure and terminate onto the lacrimal gland causing lacrimation. Other preganglionic parasympathetic fibers originating in the superior salivatory nucleus pass through the geniculate ganglion, travel with chorda tympani, and then follow the lingual nerve. These fibers terminate in the submandibular ganglion. Cell bodies of postganglionic parasympathetic fibers will then travel a short distance to innervate the submandibular and sublingual glands. The inferior salivatory nucleus projects preganglionic parasympathetic fibers to the otic ganglion. Fibers terminate here and postganglionic parasympathetic fibers travel to the parotid gland to provide innervation. The dorsal vagal nucleus located in the medulla projects preganglionic parasympathetic fibers along

the vagus nerve. This nerve exits the skull through the jugular foramen and provides widespread parasympathetic innervation of the major organ systems of the chest and abdomen. Of note, the vagus nerve only supplies parasympathetic innervation to the ascending and transverse colon. The descending colon and rectum are innervated by the parasympathetic elements of the sacral spinal cord. Increased vagal tone results in bronchoconstriction, decreased heart rate, and increased gastrointestinal motility. Unlike within the head, the vagus nerve does not have discrete ganglia prior to reaching the target end organs. Rather, the preganglionic parasympathetic axons terminate in the walls of their respective targets and the resulting postganglionic parasympathetic axons have a very short distance to travel. This is one of the principal structural differences between the sympathetic and parasympathetic nervous systems. That is, the postganglionic sympathetic axon traverses a large distance compared to the postganglionic parasympathetic axon. The principle functions of the sacral parasympathetic system are the bladder, descending colon, rectum, and pelvic organs.

The neurotransmitter used at both preganglionic parasympathetic/postganglionic parasympathetic and postganglionic parasympathetic/end organ synapses is acetylcholine. The ganglionic synapse receives acetylcholine at nicotinic receptors while the end-organ synapse receives acetylcholine at muscarinic receptors.

COMPREHENSION QUESTIONS

Refer to the following case scenario to answer questions 32.1-32.2:

A 31-year-old man comes into your office for a routine checkup that includes blood-work. In order to expedite the process, you decide to draw the man’s blood while you talk with him about his medical history. You successfully cannulate his vein, but as soon as he sees the blood filling up the tube his eyes roll back in his head and he collapses backward on the examination table. You elevate his legs and he rapidly regains consciousness.

[32.1] In this case of vasovagal syncope, from which nucleus did the preganglionic parasympathetic fibers causing cardiodepression originate?

A. Edinger-Westphal nucleus

B. Intermediolateral neurons in the sacral spinal cord

C. Dorsal motor nucleus of the vagus nerve

D. Inferior salivatory nucleus

[32.2] Where are the cell bodies of the postsynaptic nerves innervating this man’s heart located?

A. Paravertebral ganglia

B. The musculature of the heart

C. Geniculate ganglion

D. Pterygopalatine ganglion

[32.3] What neurotransmitter is released by both pre- and postganglionic neurons in the parasympathetic nervous system?

A. Norepinephrine

B. Epinephrine

C. Dopamine

D. Acetylcholine

Answers

[32.1] C. These fibers originate from the dorsal motor nucleus of the vagus nerve. Vasovagal syncope is a complicated reflex that results from a number of stimuli, one of which can be the sight of blood. The reflex involves increased parasympathetic outflow and decreased sympathetic outflow, which combine to cause hypotension sufficient to cause a loss of consciousness. The increased parasympathetic outflow causes a decrease in heart rate and myocardial contractility, and is mediated by the vagus nerve. Presynaptic parasympathetic neurons in vagus nerve originate in the dorsal motor nucleus, and supply the organs of the thorax and most of the abdominal viscera. The descending colon, rectum, and pelvic organs, however, are supplied by the sacral parasympathetic plexus, which originates in the sacral spinal cord. The Edinger- Westphal nucleus and the inferior salivatory nucleus supply parasympathetic innervation to organs in the head via the oculomotor and glossopharyngeal nerves.

[32.2] B. In the thorax and abdomen, the preganglionic neurons synapse on postganglionic neurons that reside in the walls of the organs that they innervate, in this case in the musculature of the heart. In general, the parasympathetic nervous system has preganglionic neurons that extend all the way or nearly all the way to the target organs, unlike the sympathetic nervous system, which has relatively short preganglionic neurons and long postganglionic neurons. In the head and neck, the parasympathetic preganglionic neurons synapse on postganglionic neurons in discreet ganglia close to the target organs such as the geniculate and pterygopalatine ganglia.

[32.3] D. Acetylcholine is released by all neurons in the parasympathetic nervous system, both pre- and postganglionic. The preganglionic neurons release acetylcholine onto ganglionic nicotinic receptors on the postganglionic neurons, which release acetylcholine onto muscarinic receptors in the target organs.

NEUROSCIENCE PEARLS ❖ The parasympathetic nervous system is organized into brainstem and sacral components. ❖ Parasympathetic outflow generally opposes sympathetic outflow. ❖ The vagus nerve supplies the majority of major organ systems within the chest and abdomen.

REFERENCES

Bear MF, Connors B, Paradiso M, eds. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins; 2006. 

Kandel ER, Schwartz JH, Jessell TM, eds. Principles of Neural Science. 5th ed. New York, NY: McGraw-Hill; 2000. 

Zigmond MJ, Squire LR, Bloom FE, Landis SC, Roberts JL, et al. Fundamental Neuroscience. 2nd ed. San Diego, CA: Academic Press; 1999.

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