1. Organs Controlled by the Autonomic Nervous System:

     Certain actions occur without any conscious effort, learned or unlearned. Thus the pupil of the eye constricts when one is exposed to bright light; the salivary glands secrete when food is placed in the mouth; the stomach shows waves of constriction when food is in it; the heart rate increases in an emergency; the sweat glands secrete in an overheated animal; its hair tends to stand on end; movements of the intestine occurs when it receives materials from the stomach; the organs of copulation in both sexes become suited to each other during excitation; and so forth.

     The easiest generalization that can be made about the autonomic nervous system is that it is equipped to control and modify the actions of all the organs of the body except skeletal muscle. The sites of action of autonomic nerves are smooth muscle and glands, wherever they are located. This excludes skeletal muscle except for such autonomic fibers as supply its blood vessels.

     There is no organ serviced by the autonomic nervous system which is exclusively dependent on it; and there are very few if any autonomically renovated organs which atrophy when their nerves are cut, as a skeletal muscle atrophies when its motor neurons are cut. This property of autonomy, or self-government, is responsible for the naming of the system which supplies the autonomic organs.

2. Sensory Aspects of the Autonomic Nervous System:

     The fact that autonomic organs feel pain is not news to anyone who has ever had a stomach ache, a renal colic, or a heart attack. One of the most interesting of autonomic functions has to do with the fact that there are sensory fibers in the autonomic nervous system which detect and carry information concerning blood pressure and others carry information regarding the blood gases and the total solute concentration of the blood. There are undoubtedly many other modalities of sensation carried by the autonomic nervous system. Because they are concerned with activities which do not require conscious effort, many of these sensory modalities have not even found their way into common language. The fact that words do not exist for these sensations is no evidence that the sensations do not exist. To take the example of blood pressure, it is certain that autonomic "sensation" of blood pressure existed long before the invention of the sphygmomanometer.

     What is sometimes confusing is the nature of pain from the autonomic organs. These organs normally function without producing pain, but when pain is produced in them, it is usually located inaccurately, partly because it is so unfamiliar. For example, a patient with a heart attack may complain of pain in the left arm or in the neck, though many such patients are able to locate the pain quite accurately. The appendix is usually located on the lower right side of the abdomen (See Dissectograph), but the pain of appendicitis usually begins just below the sternum.

     The stimuli which produces pain in the autonomic organs are quite different from those which affect the organs with conscious representation. Autonomic organs tend to produce pain when their muscles are stretched or when they are caused to work without adequate blood supply. They are usually quite insensitive to cutting or heat, a fact which is put to good use during surgery under local anesthetics. On the other hand, autonomic organs may produce bitter and intense pain or nausea when their attachments are stretched in handling or when they are touched by irritant chemicals.

     The source and nature of pain in ill patients is usually valuable in medical diagnosis, but it is far from infallible. Patients may have every subjective manifestation of a heart attack, yet there may be no heart disease whatever. On the other hand, the large intestine, liver, lungs and brain may be extensively invaded by a malignant tumor in a patient who has no complaints at all. Much of the art of medicine consists of evaluating the patient as a whole, and putting the pain, or look of it, into the correct context. The patient's history and his physical examination should be supplemented by the available laboratory examinations before diagnosis is made or treatment undertaken.

3. The Nature of Autonomic Control:

     Autonomic control tends to modify activity rather than cause it. It usually does so by way of chemical agents that act at sites which are themselves capable of acting independently. Thus the heart beats whether or not it receives autonomic messages, but such messages can change its rate. The fact that the heart has its own rate makes it possible for the autonomic nervous system to modify that rate in either direction. The stimulation of the vagus nerve, for example, slows the heart; stimulation of the cardiac sympathetics accelerates it--in fact the sympathetic nerves to the heart are called the accelerator nerves.

     This phenomenon, in which an intrinsic activity can be altered in either direction by two sets of nerves, is widespread in the autonomic system. For example, movements of the intestine tend to be enhanced by the parasympathetic nervous system. Remarkably, they are reduced by the sympathetic.

     Another characteristic of autonomic activity in which it differs at least qualitatively from other activity is its extreme sensitivity to changes in the chemical environment. The junction between nerve and muscle is much more open in autonomically controlled organs than in skeletal muscles. The motor neuron fiber tends to invade the muscle it supplies; the autonomic fiber lies on its surface. This is also true of the cells of the glands supplied by autonomic fibers.

     Autonomic effector organs deprived of their nerve supply show a phenomenon seen to a very limited extent in skeletal muscle: they become hypersensitive to chemical agents. This phenomenon of denervation hypersensitivity sometimes has the paradoxical result of increasing the type of activity for which autonomic nerve section has been carried out. For example, there is a distressing disease called Raynaud's disease in which paroxysms of cutaneous vasospasm in the fingers give rise to intense pain. If the vasoconstrictor autonomic fibers which supply the hand are out, the resulting denervation hypersensitivity may make the attacks even more severe than they were. A more successful surgical treatment will be described in Part 10 of this chapter.

4. Chemical Medation in the Autonomic Nervous System:

     The transmission of the autonomic impulse from nerve to muscle or gland is clearly due to the release of chemical substances at the end of the autononmic nerve fibers. The substances most often implicated are acetyl choline and catecholamines. Other substances have been suspected to transmit certain autonomic impulses. The most widely menioned ones are bradykinics, seratonin, and histamine. At the time of this writing, however, there is no compelling evidence that the last three agents are physiologically significant and they will not, therefore, be considered further.

     There is no doubt at all that acetyl choline and the catecholamines are involved in most, if not all, autonomic transmission. In order to describe their sites of action, it will be necessary to anticipate a portion of the next sections (Parts 5 and 6) of this chapter which describe the anatomy of the autonomic nervous system.

     Acetyl choline is the substance released at both preganglionic and post ganglionic endings of the parasympathetic nervous system. It is also released at the proganglionic endings of the sympathetic nervous system and those post ganglionic endings which serve the sweat glands of the skin. The catecholamines, on the hand, are released only at those post ganglionic endings of the sympathetic nervous system which serve the internal organs, including the vascular system. Thus the heart is supplied by cholinergic fibers from the parasympathetic and adrenergic fibers from the sympathetic. The term cholinergic is used to mean similar in action to acetyl choline; andrenergic is used to mean similar in action to the catcholamines.

     The skin, which has no parasympathetic supply, contains cholinergic fibers (sweat glands) and arid adrenergic fibers (blood vessels) from the sympathetic. The intestine appears to receive chiolinergic fibers from the parasympathetic nervous system, which influence its muscular activity, and adrenergic fibers from the sympathetic, which influence its circulation. A more detailed description follows in Part 7.

     Acetyl choline wherever produced is destroyed with extraordinary rapidity by the enzyme cholinesterase. The catecholamines, in contrast, are destroyed rather slowly, and the enzyme(s) which destroy them are not known with great certainty. Catechol-O-methyl transferase and monoamine oxidase have been suggested as the enzymes which destroy catecholamines, but there is no widespread agreement that these agents are basically necessary for catecholamine destruction.

5. Anatomy of the Sympathetic Nervous System:

     The sympathetic nervous system is connected to the thoracic and lumbar segments of the spinal cord and is sometimes called the thoraco-lumbar division of the autonomic. Its fibers emerge from the ventral root. Some, those which are distributed to skin and muscle, make a synapse here, the paravertebralganglion, and return to the mixed spinal nerve. Others, which are destined for internal organs, pass through the paravertebral ganglion without synapsing. These fibers course toward the midline, where they terminate in the vertebral ganglion, making a synapse with a fiber which will eventually end in one of the internal organs. All fibers before the synapse are said to be pre-ganglionic, while those after the synapse are said to be postganglionic.

     The paravertebral ganglia of the sympathetic on each side form a chain in which the ganglia are connected to each other. Though the rootlets of the chain are of thoracic and lumbar origin, the chain extends upward to supply the organs of the head and downward to supply the pelvic organs. The distribution of the sympathetic fibers is shown in Figures 160 and 161.

6. Anatomy of the Parasympathetic Nervous System:

     The parasympathetic nervous system takes its origin from some of the cranial nerves and the sacral segments of the spinal cord. This portion of the nervous system is called the craniosacral division of the autonomic nervous system, from its origin.

     Anatomically, there are some very important differences between the sympathetic and parasympathetic divisions. Perhaps the most important has to do with the location of the synapse between pre-ganglionic and post-ganglionic neurons. In the sympathetic, this synapse usually occurs in a ganglion somewhat remote from the structure innervated. The parasympathetic synapse is usually located directly in the organ which is affected. The blood supply to the parasympathetic synapse tends to correspond to the blood supply of the organ, while that of the sympathetic synapse is limited to the blood supply of the ganglion. Drugs which interfere with transmission between pre- and post-ganglionic fibers are, therefore, more likely to affect the parasympathetic than the sympathetic nervous system.. Thus, drugs which inhibit the action of acetyl choline that reach the parasympathetic preganglionic and post ganglionic terminals in large quantities are more likely to inhibit parasympathetic than sympathetic activity, even though the preganglionic sympathetic terminals are cholinergic. This has important consequences (see Part 9 of this chapter.)

     The major difference between the parasympathetic and sympathetic nervous systems has to do with the fact that the former has separate branches which operate separately; the sympathetic chain tends to discharge as a whole.

7. Tabulation of Autonomic Function:

     It was at one time believed that the parasympathetic nervous system was concerned with the resting, or vegetative, functions of the organism, such as digestion, sleep, etc. The sympathetic, on the other hand, was thought to he involved in emergency situations. To some extent, this is true; but there are so many exceptions that the student will be well advised to learn the individual functions of each system, organ by organ.

     A Table which summarizes these functions follows. In this Table, those functions which are exceptions to the vegetative emergency dichotomy will be italicized.

(1) High blood pressure follows generalized constriction of blood vessels.

(2) In asthma the airways become constricted, particularly in expiration.

(3) Faulty control of the emptying of the gall bladder may lead to biliary colic. This may result from gall stones or uncoordinated action of the gall bladder and its outlet.

(4) The stomach may empty poorly and the digestive processes impaired when sympathetic activity dominates over parasympathetic.

(5) Parasympathetic overactivity may lead to hypersecretion of gastric juices and enzymes. This may in turn lead to peptic ulcer.

(6) Sympathetic activity may produce serious reductions in renal blood flow and urinary output of water and sodium. This is a major source of difficulty in heart failure (Chapter 16).

(7) Reduced parasympathetic activity may lead to constipation.

(8) Frigidity in women and impotence in men may result from autonomic disturbances, though their mechanism is quite unclear.

(9) Excessive sweating may be diagnostic of increased sympathetic discharge.

     All of these conditions may be due to disturbances in the higher centers regulating autonomic activity rather than in the autonomic nervous system itself. Nevertheless, many of them can be treated with the autonomic drugs or by autonomic surgery.

9. Pharmacology of the Autonomic Nervous System:

     Some drugs mimic the action of one or the other branches of the autonomic nervous system. They are said to be sympathomimetic or parasympathomimetric. Adrenaline, epinephrine, is an excellent, though dangerous, sympathomimetic drug. Ephedrine is less dangerous, though less effective. The ideal parasympathomimetic drug would be acetyl choline if only it were not so quickly destroyed by cholinesterase. As it is, other choline esters, which are less readily destroyed, are much more effective. Bethanechol is often used, and rarely, pilocarpine and muscarine are used as parasympathomimetics.

     A much more effective approach to parasympathomimesis is the use of drugs which antagonize cholinesterase. Prostigimine is a safe one. The powerful anticholinesteiases like DFP are too dangerous for use.

     Sympatholytic drugs, which antagonize the actions of the catecholarnines, are divided into two chief groups. Some antagonize the excititory endings of the sympathetic, others interfere with their inhibitory effect. The former group, called the blockers, are typified by phenoxybonzamine; dibermamine is also effective. The agents which block, inhibitory receptors, are dichloroisoproterenol and pronethalol. A very widely used sympatholytic drug whose actions are only vaguely understood is guanethedine, used in treating high blood pressure. Bretylium has similar effects.

     Some of these drugs arc very new, but some are quite primitive. Rauwolfia and its many derivatives have been known for more than 300 years. These drugs cause depletion of the catecholamines from the nerves which release them. They are not only sympatholytic, but tranquilizing. It has not been decided whether the tranquilizing effect is secondary to the sympatholytic effect.

     The most effective parasympatholytic drug known is atropine or belladonna. There are others, but atropine is most widely used. It probably acts by occupying the sites in the receptor organs ordinarily filled by, and excited by, acetyl choline. Perhaps because it does not reach the sympathetic ganglia by way of the blood stream in large amounts it is not sympatholytic, even though the sympathetic synapses are cholinergic.

     The ganglion blocking agents are typified by hexamethonium. The effects are profound, and both sympathetic and parasympathetic ganglia are involved. Changes in blood vessel resistance; gastrointestinal secretion and motility and emptying of the bladder are some of the most dramatic observed effects.

     A word of caution is in order here. Every one of the agents mentioned may have unexpected side effects. Only physicians thoroughly trained in their use should employ them. No attempt will be made here to indicate how these drugs may be used in medicine.

10. Autonomic Surgery:

     Sympathectomy, partial or complete, was once a popular treatment for high blood pressure. It is a major operation and since the disease is now pretty well controlled by drugs, it has become much less used. It is most often employed for the treatment of intractable pain originating in a specific area. The operation is of some use in the treatment of Raynaud's disease, but is mentioned earlier (Part 3). If the wrong kind of sympathectomy is done (post-ganglionic), denervation hypersensitivity may aggravate the condition. Preganglionic sympathectomy may be curative, but for some reason, ganglionic blocking drugs are not very effective.

     Cutting the vagal fibers to the stomach often relieves peptic ulcers. The current status of the procedure is in doubt, for ulcers can be treated medically and vagotomy is not always curative. However, the decision must be made on an individual basis.

Continue to Chapter 7.