Sympathetic Nervous System Case File

Sympathetic Nervous System Case File

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

CASE 31

A 66-year-old Hispanic male presents to the emergency department with rightsided chest pain, weakness, and hemoptysis. He has a past medical history of hypertension, COPD, recurrent episodes of pneumonia and a 75 pack/year history for cigarettes. A Chest X-ray in the emergency department demonstrates hyperinflated lungs, emphysema, and a large right-sided mass. Internal medicine admits the patient to the hospital for further evaluation. A neurologist is consulted to evaluate his new-onset weakness. His right upper extremity is diffusely weak but there is profound weakness in his intrinsic hand muscles. He is also noted to have right ptosis and anisocoria; his right pupil is 2 mm and reactive and his left pupil is 5 mm and reactive. It is soon found that he has a Pancoast tumor causing Horner syndrome.

• In what part of the lung are Pancoast tumors found?
• What explains the anisocoria?
• What explains the ptosis?

ANSWERS TO CASE 31: SYMPATHETIC NERVOUS SYSTEM

Summary: A 66-year-old man with frank pulmonary pathology and a heavy smoking history, presents with a new chest mass, anisocoria, and muscle weakness.

• Location: Pancoast tumors are found in the apex of the lung.
• Anisocoria: Tumor invasion of the sympathetic chain resulting in ipsilateral unopposed parasympathetic tone to the papillary constrictor muscle causing miosis.
• Ptosis: Also caused by tumor invasion of the sympathetic network. In this case, loss of innervation to Muller muscle causes ptosis.

CLINICAL CORRELATION

This is a classic presentation of a Pancoast tumor that invades the apex of the lung. These are often caused by squamous cell carcinoma of the lung. Patients often have ipsilateral shoulder and medial arm pain. These tumors often invade the brachial plexus but can also compromise the lower cervical

or upper thoracic spinal nerve roots. Therefore, there is often sensory loss in the C8-T1 distributions. This results in sensory loss of the ipsilateral dorsomedial forearm and into the fifth and medial half of the fourth digits. There is often compromise of peripheral sympathetic chain and the stellate ganglion.

This results in disruption of the sympathetic tone that returns to the head causing ptosis and miosis. Additionally, if the tumor invades the sympathetic fibers at or above the level of the carotid bifurcation, one would expect to find anhydrosis of the entire ipsilateral face. If the tumor is distal to this point, one would expect to find anhydrosis on the ipsilateral medial forehead and medial ipsilateral nose. It is important to remember that disruption of the sympathetic fibers at any point from their origin in the hypothalamus to their ascension along the carotid artery can result in Horner syndrome.

APPROACH TO SYMPATHETIC NERVOUS SYSTEM

Objectives

1. Understand the anatomy of the sympathetic nervous system (see Figure 31-1).
2. Know the neurotransmitters used by the sympathetic nervous system at the different synapses.
3. Be able to discuss the effects of the sympathetic stimulation of major end organs.

Figure 31-1. The sympathetic (thoracolumbar) division of the autonomic nervous system is noted on the left. (With permission from Kandel ER, Schwartz JH, Jessell TM. Principles of Neural Science. 4th ed. New York, NY: McGraw-Hill; 2000:964.)

Definitions

Thoracolumbar nervous system: The sympathetic nervous system as defined with respect to the spinal cord levels containing the cell bodies of preganglionic sympathetic nerves.

Paravertebral ganglion: The sympathetic trunk containing the terminal fibers of white communicating rami and the cell bodies of gray communicating rami. This is a bilateral structure.

Superior cervical ganglion: Analogous to the paravertebral ganglion but has cell bodies of gray communicating rami that will eventually terminate in the head.

Prevertebral ganglia: The celiac, superior mesenteric, and inferior mesenteric ganglia where white communicating rami terminate on the cell bodies of gray communicating rami that terminate onto most abdominal and retroperitoneal viscera.

DISCUSSION

The sympathetic nervous system 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.

The central organization of the sympathetic nervous system, which regulates the “fight or flight” responses, is best understood by focusing on the hypothalamus. At this level, both afferent and efferent information is processed and the tone of the sympathetic 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 sympathetic 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 sympathetic drive. By projecting to the hypothalamus, these cortical areas are able to manifest their output by altering the tone of the sympathetic nervous system. Most sympathetic fibers originate in the lateral and posterior regions of the hypothalamus. From here they descend without crossing into the lateral tegmentum of the midbrain, pons, medulla, and into the spinal cord. These axons terminate in the interomediolateral cell column of the spinal cord from C8-L2. Because the sympathetic nervous system is confined to this region of termination, it often carries the designation of thoracolumbar. The peripheral sympathetic nervous system begins with cell bodies located in the interomediolateral cell column of the gray matter of the spinal cord. These cell bodies project their preganglionic myelinated axons, or white communicating rami, through the ventral root exit zone of the spinal cord, through the ventral rootlet, and into the spinal nerve at each level. The white communicating rami will terminate in one of two structures: the paravertebral ganglion running along side the vertebral column or the prevertebral ganglia in the posterior abdominal cavity (note that the paravertebral trunks are paired structures on both sides of the vertebral column). The three separate prevertebral ganglia include the celiac ganglion, the superior mesenteric ganglion, and the inferior mesenteric ganglion. By far, the majority of the sympathetic fibers traverse the T5-L2 spinal nerves to their respective targets. The prevertebral and paravertebral ganglia accept the preganglionic sympathetic fibers and contain the cell bodies of postganglionic unmyelinated sympathetic fibers, or gray communicating rami. The axons of these cell bodies will terminate upon their end organ targets including sweat glands, intestinal glands, cardiac and pulmonary tissue among others. Of note, the adrenal glands receive innervation by white communicating rami without synapse. The postganglionic sympathetic component of the adrenal gland is considered to occur when the gland releases its chemical product, epinephrine, into the blood stream.

In comparison to parasympathetic nervous system fibers, sympathetic preganglionic fibers are short and the postganglionic fibers are long. One preganglionic fiber innervates many postganglionic fibers, and it is this divergence that amplifies sympathetic outputs and coordinates sympathetic activation across different spinal levels (see Figure 31-1).

The head receives its sympathetic network from C8-T2 cord levels and terminate in the superior cervical ganglion. Postganglionic sympathetic fibers course along the internal carotid arteries to innervate the salivary, lacrimal, and sweat glands; smooth muscle; and blood vessels of the head. The arms receive their postganglionic sympathetic innervation from the lower cervical and upper thoracic ganglia. The heart receives its sympathetic tone from the upper thoracic ganglion, while the abdominal ganglia receive their input from T5-T9/T10. The pelvis, legs, and descending colon are supplied by the upper lumbar ganglia.

It is important to remember that the sympathetic nervous system is not solely a visceral motor system. As mentioned earlier, there are visceral afferent pathways too. The cell bodies of these sensory axons are located in the dorsal sensory ganglion within the thecal sac and their afferent projections can terminate locally on the intermediolateral cell column to affect local reflexes or onto the dorsal horn of the spinal gray resulting in central communication of visceral sensations such as a full bladder.

The neurotransmitter profile of the sympathetic nervous system is crucial for understanding the pharmacological interventions employed to treat many medial illnesses. The initial synapse of pre- and postganglionic neurons uses acetylcholine as a neurotransmitter while the postganglionic to end organ target synapse uses norepinephrine. One exception is the adrenal medulla, which uses acetylcholine at the synapse of the preganglionic sympathetic to adrenal gland to stimulate release of epinephrine into the bloodstream. Two other exceptions that utilize acetylcholine release in the postganglionic sympathetic synapse to target organ are sweat glands and blood vessels.

Sympathetic nervous system neurotransmitter receptors are classified into alpha and beta with subgroupings of alpha-1, alpha-2 and beta-1, beta-2. Stimulation of alpha-1 receptors causes vasoconstriction, decreased gastrointestinal motility, and pupillary dilation. Alpha-2 receptors are located on the presynaptic terminal and upon stimulation cause attenuation of neurotransmitter release into the synaptic cleft. Beta-1 receptors increase heart rate and heart contractility. Beta-2 receptors cause vasodilation and bronchodilation.

COMPREHENSION QUESTIONS

Refer to the following case scenario to answer questions 31.1-31.3:

A 73-year-old man comes into your office complaining of a droopy right eyelid ever since he has surgery to “clean out his neck artery” several weeks ago. He also notes that he does not think the right half of his face sweats as much as the left. On examination you also note that his right pupil is several millimeters smaller than his left, but that both are reactive to light. You suspect that this man has Horner syndrome as a complication of his recent carotid endarterectomy.

[31.1] Where are the cell bodies of the damaged nerves located in this man?

A. Paravertebral ganglia

B. Prevertebral ganglia

C. Intermediolateral column of the thoracic spinal cord

D. Superior cervical ganglion

[31.2] What neurotransmitters are normally released onto these damaged postganglionic neurons by the preganglionic neurons?

A. Acetylcholine

B. Norepinephrine

C. Dopamine

D. Epinephrine

[31.3] What neurotransmitter is normally released by these damaged postganglionic neurons onto glandular and vascular targets?

A. Acetylcholine

B. Norepinephrine

C. Dopamine

D. Epinephrine

Answers

[31.1] D. In the face, the ganglion involved is the superior cervical ganglion. This man has Horner syndrome as a complication of his carotid endarterectomy. The sympathetic nerves that innervate the face run along the carotid artery and can be damaged (although rarely) with excess dissection around the artery in surgery. One feature of the sympathetic nervous system is that it has relatively short preganglionic axons, which synapse in ganglia near the spinal cord, and long postganglionic axons that then project from these ganglia to the end organs. Axons from cell bodies in the superior cervical ganglion ascend along the carotid artery and then follow its branches to their targets in the face and head. The first-order neurons that synapse in the superior cervical ganglion have their cell bodies in the intermediolateral column of the thoracic cord.

[31.2] A. All preganglionic autonomic neurons (sympathetic and parasympathetic) release acetylcholine at autonomic ganglia. This acetylcholine activates ganglionic nicotinic acetylcholine receptors located on postganglionic neurons, triggering action potentials.

[31.3] B. For the most part, postganglionic sympathetic neurons release norepinephrine onto their targets, including glands and blood vessels. The only targets that do not get norepinephrine neurotransmission are sweat glands. Sympathetic neurons innervating sweat glands release acetylcholine onto muscarinic receptors on the sweat glands.

NEUROSCIENCE PEARLS ❖ Most lesions of the sympathetic nervous system above the thoracic spine will cause an ipsilateral Horner syndrome. ❖ The various adrenergic receptors form the basis of pharmacological intervention for heart rate control, blood pressure control, and airway control. ❖ The hypothalamus is the principle nucleus and origin of the sympathetic nervous system.

REFERENCES

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

Purves D, Augustine GJ, Fitzpatrick D, et al. Neuroscience. 3rd ed. Sunderland, MA: Sinauer Associates, Inc; 2004. 

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

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