Neuroanatomy, Sympathetic Nervous System

Structure and Function

The sympathetic nervous system is composed of many pathways that perform a variety of functions on various organ systems. The preganglionic neurons of the SANS arise from the thoracic and lumbar regions of the spinal cord (T1 to L2) with the cell bodies distributed in four regions of the gray matter in the spinal cord bilaterally and symmetrically.[1][2] As opposed to the parasympathetic nervous system, the first-order neurons of the SANS are short before synapsing on postsynaptic neurons found within sympathetic ganglia. Similar to the PANS, the neurotransmitter used at this junction is acetylcholine. This acetylcholine activates nicotinic receptors. These postganglionic neurons then travel to their effector sites and release the neurotransmitters epinephrine or norepinephrine, except for sympathetic innervation of sweat glands and the arrectores pili muscles, the small muscles attached to hair follicles, which use acetylcholine as their postganglionic neurotransmitter.[3] These neurotransmitters act on adrenergic receptors. Among the adrenergic receptors are alpha-1 (coupled to a Gq and works through the IP3/Ca2+ pathway), alpha-2 (coupled to Gi and works through decreasing the cAMP pathway), and beta-1 and beta-2 (coupled to Gs and works through increasing the cAMP pathway).[4] Whether beta-1 and beta-2 are excitatory or inhibitory depends on the tissue on which it is located. These receptors are located on various parts of the body and regulate the actions of the SANS.

The functions of the sympathetic nervous system are expansive and involve many organ systems and various types of adrenergic receptors.

The effects in which SANS acts in direct contrast to the PANS function include the following:

• In the eye, sympathetic activation causes the radial muscle of the iris (alpha-1) to contract, which leads to mydriasis, allowing more light to enter. Furthermore, the ciliary muscle (beta-2) relaxes, allowing for far vision to improve.
• In the heart (beta-1, beta-2), sympathetic activation causes an increased heart rate, the force of contraction, and rate of conduction, allowing for increased cardiac output to supply the body with oxygenated blood.
• In the lungs, bronchodilation (beta-2) and decreased pulmonary secretions (alpha-1, beta-2) occur to allow more airflow through the lungs.
• In the stomach and intestines, decreased motility (alpha-1, beta-2) and sphincter contraction (alpha-1), as well as contraction of the gallbladder (beta-2), occur to slow down digestion to divert energy to other parts of the body.
• The exocrine and endocrine pancreas (alpha-1, alpha-2) decreases both enzyme and insulin secretion.
• In the urinary bladder, there is relaxation of the detrusor muscle and contraction of the urethral sphincter (beta-22) to help stop urine output during sympathetic activation.
• The kidney (beta-1) increases renin secretion to increase intravascular volume.
• The salivary glands (alpha-1, beta-2) work through small volumes of potassium and water secretion. 

Actions of SANS which do not oppose those of the PANS include the following:

• There is strong constriction through the alpha-1 receptor in arterioles of the skin, abdominal viscera, and kidney, and weak constriction through the alpha-1 and beta-2 receptors in the skeletal muscle.
• In the liver, increased glycogenolysis and gluconeogenesis (alpha-1, beta-2) occur to allow for glucose to be available for energy throughout the body.
• In the spleen, there is a contraction (alpha-1).
• Sweat glands and arrector pili muscles (muscarinic) work to increase sweating and erection of hair to help cool down the body.
• Lastly, the adrenal medulla (nicotinic receptor) increases the release of epinephrine and norepinephrine to act elsewhere in the body.[1]

Embryology

Neurons of the peripheral autonomic nervous system, which includes both the sympathetic nervous system and parasympathetic nervous system, arise from neural crest cells that originate between the neural and non-neural ectoderm. They form the dorsal neural folds as the folds themselves form the neural tube.[5]

Physiologic Variants

Aging has various effects on the sympathetic nervous system. Research has demonstrated that with increased age that baroreceptors of the heart decrease and become less sensitive; there is a compensatory increase in cardiovascular SANS activity and a reduction in PANS activity. However, both sympathetic and parasympathetic nervous activity to the iris decreases with aging, which is consistent with the general decline of peripheral somatic nerve function.[6] Research has also shown that baseline levels of noradrenaline levels increase with age resulting in an elevated basal SANS activation, while the reactivity becomes reduced with aging.[7] This increase in activation plays a role, among other disease processes, in both age-related hypertension and heart failure.[8]

Surgical Considerations

Horner syndrome is a complication born from interruption of the sympathetic innervation to the eye and adnexa at varying levels, most commonly of the neck, resulting in increased parasympathetic input. It presents with the classic triad of ipsilateral ptosis, pupillary miosis, and facial anhidrosis. It can be a complication of neck surgeries that damage the sympathetic input.[9] There are even reports after minimally invasive thyroidectomy.[10] For more information on Horner syndrome, please refer to our accompanying article.[11]

Hyperhidrosis, otherwise known as excessive sweating, is a common indication for minimally invasive thoracic sympathectomy. Hyperhidrosis is excessive sweating beyond the organism’s physiological need to sweat to have a temperature within an adequate range. Removing the sympathetic input to the part of the body affected by hyperhidrosis is an acceptable and well-tolerated treatment.[12] Thorascoposic sympathectomy can also be useful to treat severe Raynaud syndrome, defined as episodic vascular spasms and digital ischemia secondary to cold or emotional stimuli.[13]

Clinical Significance

The clinical significance of the sympathetic nervous system is vast as it affects many organ systems. Of the many physiological and pathological processes, pheochromocytoma, erections and priapism, diabetic neuropathy, and orthostatic hypotension are described below.

Pheochromocytomas are tumors that arise from chromaffin cells present in the adrenal medulla or paraganglion cells that secrete excess amounts of catecholamines (norepinephrine, epinephrine). Because of this catecholamine release, the symptoms are largely that of sympathetic activation, such as hypertension, tachycardia/palpitations, hyperglycemia, and diaphoresis.[14]

Erections are a product of parasympathetic activity. In the resting state, the SANS predominates, and the penis remains flaccid. However, if the sympathetic fibers to the penis are damaged or compromised, a sustained erection of over 4 hours, called priapism, can occur and result in devastating consequences to the penis. This condition can result from spinal cord or cauda equina injury as the sympathetic input is damaged, and the parasympathetic tone dominates.[15] Nevertheless, SANS also contributes to the normal sexual function of a man. Sympathetic stimulation of the male genitals causes sperm emission, which is sensed by the hypogastric nerve.[16]

Diabetic autonomic neuropathy is one of the most common causes of sympathetic nerve neuropathy. This sympathetic denervation can lead to impaired myocardial coronary blood flow and reduced myocardial contractility.[17] Diabetic neuropathy plays a crucial role in morbidity and mortality in patients with both type 1 and type 2 diabetes mellitus and causes dysfunction of many systems, including the heart, the Gastroenterol tract, the genitourinary system, and sexuality. As it is well established that hyperglycemia is the primary driver of this diabetic complication, the clinician must establish early and sustained intensive glycemic control to prevent or delay the onset and slow the progression of autonomic dysfunction. However, this strategy seems to be more effective in type 1 versus type 2 diabetic patients.[18] 

Lastly, orthostatic hypotension is a common problem caused by the failure of noradrenergic neurotransmission. It is defined as a drop of systolic blood pressure by at least 20 mmHg or diastolic by 10 mmHg.[19] It is caused by a wide variety of disease processes, including but not limited to pure autonomic failure, multiple system atrophy, and autonomic neuropathies that damage the SANS.[20]