The primary responsibilities of the autonomic nervous system are to regulate homeostatic mechanisms in the body, which is also part of what the endocrine system does. The key to understanding the autonomic system is to explore the response pathways—the output of the nervous system. The way we respond to the world around us, to manage the internal environment on the basis of the external environment, is divided between two parts of the autonomic nervous system. The sympathetic division responds to threats and produces a readiness to confront the threat or to run away: the fight-or-flight response. The parasympathetic division plays the opposite role. When the external environment does not present any immediate danger, a restful mode descends on the body, and the digestive system is more active.
The sympathetic output of the nervous system originates out of the lateral horn of the thoracolumbar spinal cord. An axon from one of these central neurons projects by way of the ventral spinal nerve root and spinal nerve to a sympathetic ganglion, either in the sympathetic chain ganglia or one of the collateral locations, where it synapses on a ganglionic neuron. These preganglionic fibers release ACh, which excites the ganglionic neuron through the nicotinic receptor. The axon from the ganglionic neuron—the postganglionic fiber—then projects to a target effector where it will release norepinephrine to bind to an adrenergic receptor, causing a change in the physiology of that organ in keeping with the broad, divergent sympathetic response. The postganglionic connections to sweat glands in the skin and blood vessels supplying skeletal muscle are, however, exceptions; those fibers release ACh onto muscarinic receptors. The sympathetic system has a specialized preganglionic connection to the adrenal medulla that causes epinephrine and norepinephrine to be released into the bloodstream rather than exciting a neuron that contacts an organ directly. This hormonal component means that the sympathetic chemical signal can spread throughout the body very quickly and affect many organ systems at once.
The parasympathetic output is based in the brain stem and sacral spinal cord. Neurons from particular nuclei in the brain stem or from the lateral horn of the sacral spinal cord (preganglionic neurons) project to terminal (intramural) ganglia located close to or within the wall of target effectors. These preganglionic fibers also release ACh onto nicotinic receptors to excite the ganglionic neurons. The postganglionic fibers then contact the target tissues within the organ to release ACh, which binds to muscarinic receptors to induce rest-and-digest responses.
Signaling molecules utilized by the autonomic nervous system are released from axons and can be considered as either neurotransmitters (when they directly interact with the effector) or as hormones (when they are released into the bloodstream). The same molecule, such as norepinephrine, could be considered either a neurotransmitter or a hormone on the basis of whether it is released from a postganglionic sympathetic axon or from the adrenal gland. The synapses in the autonomic system are not always the typical type of connection first described in the neuromuscular junction. Instead of having synaptic end bulbs at the very end of an axonal fiber, they may have swellings—called varicosities—along the length of a fiber so that it makes a network of connections within the target tissue.
Autonomic nervous system function is based on the visceral reflex. This reflex is similar to the somatic reflex, but the efferent branch is composed of two neurons. The central neuron projects from the spinal cord or brain stem to synapse on the ganglionic neuron that projects to the effector. The afferent branch of the somatic and visceral reflexes is very similar, as many somatic and special senses activate autonomic responses. However, there are visceral senses that do not form part of conscious perception. If a visceral sensation, such as cardiac pain, is strong enough, it will rise to the level of consciousness. However, the sensory homunculus does not provide a representation of the internal structures to the same degree as the surface of the body, so visceral sensations are often experienced as referred pain, such as feelings of pain in the left shoulder and arm in connection with a heart attack.
The role of visceral reflexes is to maintain a balance of function in the organ systems of the body. The two divisions of the autonomic system each play a role in effecting change, usually in competing directions. The sympathetic system increases heart rate, whereas the parasympathetic system decreases heart rate. The sympathetic system dilates the pupil of the eye, whereas the parasympathetic system constricts the pupil. The competing inputs can contribute to the resting tone of the organ system. Heart rate is normally under parasympathetic tone, whereas blood pressure is normally under sympathetic tone. The heart rate is slowed by the autonomic system at rest, whereas blood vessels retain a slight constriction at rest.
In a few systems of the body, the competing input from the two divisions is not the norm. The sympathetic tone of blood vessels is caused by the lack of parasympathetic input to the systemic circulatory system. Only certain regions receive parasympathetic input that relaxes the smooth muscle wall of the blood vessels. Sweat glands are another example, which only receive input from the sympathetic system.
The autonomic system integrates sensory information and higher cognitive processes to generate output, which balances homeostatic mechanisms. The central autonomic structure is the hypothalamus, which coordinates sympathetic and parasympathetic efferent pathways to regulate activities of the organ systems of the body. The majority of hypothalamic output travels through the medial forebrain bundle and the dorsal longitudinal fasciculus to influence brain stem and spinal components of the autonomic nervous system. The medial forebrain bundle also connects the hypothalamus with higher centers of the limbic system where emotion can influence visceral responses. The amygdala is a structure within the limbic system that influences the hypothalamus in the regulation of the autonomic system, as well as the endocrine system.
These higher centers have descending control of the autonomic system through brain stem centers, primarily in the medulla, such as the cardiovascular center. This collection of medullary nuclei regulates cardiac function, as well as blood pressure. Sensory input from the heart, aorta, and carotid sinuses project to these regions of the medulla. The solitary nucleus increases sympathetic tone of the cardiovascular system through the cardiac accelerator and vasomotor nerves. The nucleus ambiguus and the dorsal motor nucleus both contribute fibers to the vagus nerve, which exerts parasympathetic control of the heart by decreasing heart rate.
The autonomic system is affected by a number of exogenous agents, including some that are therapeutic and some that are illicit. These drugs affect the autonomic system by mimicking or interfering with the endogenous agents or their receptors. A survey of how different drugs affect autonomic function illustrates the role that the neurotransmitters and hormones play in autonomic function. Drugs can be thought of as chemical tools to effect changes in the system with some precision, based on where those drugs are effective.
Nicotine is not a drug that is used therapeutically, except for smoking cessation. When it is introduced into the body via products, it has broad effects on the autonomic system. Nicotine carries a risk for cardiovascular disease because of these broad effects. The drug stimulates both sympathetic and parasympathetic ganglia at the preganglionic fiber synapse. For most organ systems in the body, the competing input from the two postganglionic fibers will essentially cancel each other out. However, for the cardiovascular system, the results are different. Because there is essentially no parasympathetic influence on blood pressure for the entire body, the sympathetic input is increased by nicotine, causing an increase in blood pressure. Also, the influence that the autonomic system has on the heart is not the same as for other systems. Other organs have smooth muscle or glandular tissue that is activated or inhibited by the autonomic system. Cardiac muscle is intrinsically active and is modulated by the autonomic system. The contradictory signals do not just cancel each other out, they alter the regularity of the heart rate and can cause arrhythmias. Both hypertension and arrhythmias are risk factors for heart disease.
Other drugs affect one division of the autonomic system or the other. The sympathetic system is affected by drugs that mimic the actions of adrenergic molecules (norepinephrine and epinephrine) and are called sympathomimetic drugs. Drugs such as phenylephrine bind to the adrenergic receptors and stimulate target organs just as sympathetic activity would. Other drugs are sympatholytic because they block adrenergic activity and cancel the sympathetic influence on the target organ. Drugs that act on the parasympathetic system also work by either enhancing the postganglionic signal or blocking it. A muscarinic agonist (or parasympathomimetic drug) acts just like ACh released by the parasympathetic postganglionic fiber. Anticholinergic drugs block muscarinic receptors, suppressing parasympathetic interaction with the organ.