Library:Autonomic systems

A Ray Peat newsletter, 2007-12-29.

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People like Walter Cannon and Wilhelm Reich popularized the idea of the autonomic nervous system, but they were just systematizing ideas that had been developing since the beginning of the century. Their views were the context in which Selye's idea of stress developed.

The anatomical components of the nervous system that were called the sympathetic (“fight or flight,” adrenergic) system and the parasympathetic (“vegetative”) system are still important factors in physiological thinking, and despite the great complexity that has grown up around them, there is still a tendency to identify the systems with polarities of mood or emotion. The idea of polarities is useful, but it easily leads to error.

(The sympathetic system includes a chain of ganglia along the spine, and its functions include dilating the pupils and accelerating the heart. The parasympathetic system is also called the cranio-sacral system, from the location of its ganglia, and among its functions are slowing the heart and constricting the pupils. However, despite several decades of research, the actions of “sympathetic” and “parasympathetic” nerves in most organs aren't understood.)

If the “adrenaline side” of the nervous system is responsible for the reactions to pain and threat, reactions of fear and rage, then the opposite side tends to be given attributes such as peace and pleasure, and the fact that these oppositions are often true has led to a climate in which the adrenergic reactions are seen as “bad,” and the opposite reactions as “good.” When adrenalin was identified as an agent of the sympathetic nervous system, there was a search for the “opposing” agent of the parasympathetic system. Histamine was an early candidate, before acetylcholine was discovered to be the main parasympathetic agent. This view of histamine was fostered by the older idea of “trophic nerves,” which easily became identified with the parasympathetic system. When acetylcholine was identified as the transmitter or agent of the parasympathetic system, it tended to take on many of the qualities, including the “trophic” functions, that had grown up around the idea of the parasympathetic system, but the emphasis on acetylcholine led to a general neglect of the associations of histamine, and the mast cells that produce much of it, with the autonomic nervous system. (The current trend seems to be emphasizing a close integration of mast cell function with nervous function.) Nitric oxide has recently been identified as another parasympathetic “transmitter.” Nitric oxide and histamine are both very important factors in degenerative inflammatory diseases, but their association with the parasympathetic nervous system has given them an aura of benevolence.

I think it's useful to compare the autonomic nervous system with the pituitary, not just because some of the pituitary hormones are called “trophic” hormones (e.g., luteotrophic, adrenocorticotrophic), but because their important adaptive functions can themselves be the cause of serious problems. An excess of the thyroid stimulating hormone, for example, causes degeneration and cancer development in the thyroid gland, and animals deprived of their pituitary gland, but given thyroid, live longer than intact animals.

If slaves are starved and beaten frequently, they aren't very productive, they don't live long, and they might rebel. Workers that are healthy and working for a common goal that they understand are more productive. Cells that are well energized perform their functions with minimal cues, but deprived cells that have to be forced to function are likely to die unexpectedly, or to reproduce inappropriately, or to change their identity.

Professors often make a strong impression on their students, but, especially in technical or scientific fields, they usually do this by controlling the discourse, so that radical questioning is excluded. What they don't know “isn't knowledge.” Under the pressure of “getting a professional education,” students appreciate organizing principles and mnemonic devices, but this gives traditional ways of systematizing knowledge tremendous power that, in practice, is far more important than mere experimental results. (Experiments that don't acknowledge the ruling metaphors are almost universally considered inadmissible, unpublishable.)

Some obvious questions about the autonomic system have been commonly ignored or minimized by physiologists. If “stress” is the stimulus that causes the sympathetic system to increase its activity, what is the stimulus for increased activity of the parasympathetic system? What accounts for the relative balance between the two sides of the system, or their imbalance? The fact that the answers aren't obvious has left the questions largely to psychiatrists and psychologists. Wilhelm Reich, who tried to provide answers in terms of developmental interactions between the organism and its environment, found that the question led him to investigate psychosomatic disease, sexual repression, cancer, and fascism, with disastrous results for himself.

Chinese medicine was familiar with many of the functions of the autonomic nervous system at a time when western medicine was organized around “the humors.” It's easy for contemporary “western” people to see that the “winds” and the hot and cold principles of Chinese tradition are metaphors, but they are reluctant to see that their own system has grown up within very similar traditional metaphoric polarities.

The successes of even a good metaphor can cause people to neglect details that could support a more complete and accurate image of reality.

Contemporary science carries a load of bad metaphors, because the educational system doesn't tolerate a critical attitude. Potentially, a good metaphor (e.g., Vernadsky's suggestion that an organism is “a whirlwind of atoms”) could blow away many bad metaphors, but the present organization of science is tending in the other direction: Commercial interests are creating a culture in which their metaphors are replacing the traditional science in which there was a certain amount of honest intellectual exploration.

In talking about consciousness, sleep, stress, biological rhythms, aging, and energy, I have often focussed on the efficient use of oxygen for energy production by the mitochondria, i.e., cellular respiration. Every situation demands a special kind of adaptation, and each kind of adaptation requires a special distribution of cellular and organic activity, with its supporting local respiratory activity.

There is a lot of local self-regulation in the adapting organism, for example when the activated tissue produces increased amounts of carbon dioxide, which dilates blood vessels, delivering more oxygen and nutrients to the tissue. But the distribution of excitation, and the harmonious balancing of the organism's resources and activities, is achieved by the actions of the cortex of the brain, acting on the subordinate nerve nets, adjusting many factors relating to energy production and use.

On the level of the mitochondria, adrenaline and acetylcholine have slightly different effects. (Metabolic studies with isolated mitochondria are so remote from the normal cellular condition that their results are nothing more than a hint of what might be occurring in the cell.) Acetylcholine appears to shift the proportion of the fuels used (increasing the oxidation of alpha-ketoglutarate, with the production of carbon dioxide) and increasing the efficiency of energy conservation (phosphorylation, producing ATP) so that less oxygen is needed, while adrenaline increases the rate of oxygen consumption (and succinate oxidation). This would be consistent with F. Z. Meerson's conception of the parasympathetic function as one of the “stress limiting” systems.

On the level of the whole cell, organ, and organism, the parasympathetic function limits oxygen consumption in a variety of ways, including the reduction of blood flow. Acetylcholine, like histamine and serotonin, activates glycolysis, the conversion of glucose to lactic acid, which provides energy in the absence of oxygen.

The effects of a little adrenaline, and a lot of adrenaline, are very different, with a high concentration of adrenaline decreasing the efficiency of phosphorylation. In the stressed heart, this effect of excess adrenaline can be fatal, especially when it is combined with adrenaline's acceleration of clotting, liberation of fatty acids, and frequently of calcium, and constriction of blood vessels.

Seventy years ago, autonomic control of blood vessels seemed to be a matter of nerve fibers that constrict them, and other fibers that cause them to dilate, but that idea hasn't worked for a long time.

Ever since I noticed that the students in our physiology lab who tried to use adrenaline to revive their rats weren't successful, I have wondered about the television shows in which adrenaline is given to patients with heart problems. Under some conditions adrenaline does increase circulation to the heart, but extreme stress doesn't seem to be among those conditions.

Too much serotonin, histamine, acetylcholine, and polyunsaturated fatty acids, like too much adrenalin, can cause spasms of the coronary arteries, along with disturbances of mitochondrial respiration. In stress, these substances are almost sure to be present in excess. (Anti-serotonin drugs are effective for a variety of heart problems, and other degenerative diseases.)

By increasing the production of lactic acid and the loss of carbon dioxide, exaggerated nervous stimulation (especially the excess of acetylcholine, histamine, and serotonin) can cause a variety of problems, including generalized vasoconstriction and systemic alkalosis, as well as increased intracellular alkalinity. This metabolic pattern is characteristic of many kinds of stress, including cancer. (Elsewhere, I have referred to this pattern as “relative hyperventilation.”) The metabolic effects probably account for some of the “paradoxical” effects of the autonomic agents.

When nutrition and thyroid function, light, atmospheric pressure, and other conditions are favorable, the autonomic transmitters (e.g., acetylcholine, histamine, serotonin, adrenalin) and pituitary hormones and other “signal substances” are kept within safe limits.

Because the substances released from various cells under the influence of the autonomic nerves (histamine and serotonin, for example) stimulate cell division, injuries which produce clots and vascular spasms will also stimulate the formation of new blood vessels, a process that is essential for the adaptation of tissues to prolonged stress.

These stress-induced agents are appropriately included in the “vegetative” (parasympathetic) nervous system, because they promote vegetation, i.e., the proliferation of substance.

Adrenaline, and the sympathetic nerves, have the opposite function, of restraining cell division, and they also oppose the pro-inflammatory functions of those parasympathetic agents.

Estrogen tends to shift autonomic balance toward the parasympathetic side, away from the sympathetic/adrenergic. Recalling that stress, hypothyroidism, and aging increase the activity of aromatase in various tissues, with local production of estrogen, and that tissue-bound estrogen stays at a high level in postmenopausal women despite the lower level of estrogen in the serum, it's worthwhile looking at the effects of estrogen on the various components of the so-called autonomic nervous system.

One injection of estrogen can induce a large increase in the number of sympathetic nerves in the ovaries. At menopause, a similar “invasion” of sympathetic nerves occurs. The polycystic ovary (which is even more common after menopause than before, and some studies have found the condition in 20% of premenopausal women) responds to estrogen by producing nerve growth factor(s), and growing a large number of new sympathetic nerves. Although the hyperestrogenism associated with the polycystic ovary syndrome has many harmful effects, the invasion of the ovary by adrenergic nerves apparently protects it from the development of cancer.

Parasympathetic nerves, pituitary hormones and mast cells activate the ovaries. The number of mast cells in the ovaries is increased by the pituitary hormones (including the thyroid stimulating hormone), and by estrogen. Estrogen is the most potent of these hormones in causing the cells to release histamine. The overgrowth of the sympathetic nerves in the polycystic ovary causes the number and activity of mast cells to decrease, possibly as a protective adaptation against excessive stimulation from the many pro-inflammatory factors. The mast cells are needed for the follicles to rupture, so their suppression prevents ovulation.

The nervous system is closely involved in controlling the growth of tissues, and it has been argued (R.E. Kavetsky reviewed the subject in his book, emphasizing the role of depression in development of cancer) that cancer results from reduced activity of the sympathetic nerves, or unopposed action of the parasympathetic system. That stress has a role in cancer is acknowledged by the scientific establishment, but the nervous system's direct involvement in the regulation of cellular metabolism, cell division, and other processes that are central to the cancerous state is either flatly denied or simply ignored.

Although mast cells have been known to be a common component of tumors for many years, it is only recently that antihistamines and other antiinflammatory drugs have been recognized as valuable therapies in cancer. The whole issue of the role of nerves in tumor development and physiology has been submerged by the mystique of the “intrinsically bad cancer cell.”

In Alzheimer's disease, there has been a great investment in the doctrine that drugs to promote the function of cholinergic (acetylcholine forming) nerves will restore lost mental function, or at least retard the progression of the disease. The success of anticholinergic drugs in treating several degenerative brain diseases is probably embarrassing to the companies whose cholinergic-intensifying drugs aren't very successful. Conveniently for them, these formerly “anticholinergic” drugs are now being called anti-excitotoxic or anti-glutamatergic drugs. There is no serious conflict in the terminology, since the cholinergic processes (like the serotonergic processes) are closely associated with excitotoxic nerve damage. The cholinergic drugs will probably be sold as long as their patents are effective, and then will be quietly forgotten.

The modern conception of pharmacology, with receptors and transmitters turning functions on or off, has turned into an unproductive and dangerous scholasticism. No one will ever successfully count the number of transmitter angels dancing on the variable sites of the variable receptor molecules. The functional “meaning” of a receptor or transmitter changes according to circumstances, and the effect of activating a particular nerve depends on surrounding conditions, and on preceding conditions. Each cell integrates stimuli adaptively.

If no reflex is simply mechanical and innate, then all reflexes are conditional. (M. Merleau-Ponty argued against the validity of the reflex concept itself, because of this conditionality.) P. K. Anokhin's concept of the “Acceptor of Action” (described in my book, Mind and Tissue) provides an image in which we can see the “set-points” for the relatively “autonomic” reflexes as reflections of the general needs of the organism. The local tissue reflexes, the organ reflexes, the spinal reflexes, etc., are variable, according to their energetic resources, and according to the way in which they are organized under the influence of the cerebral cortex and the environment.

The reality is more complex than the philosophy of the drug industry imagines, but the solutions of problems can be much simpler, if we think in terms of energetic support, rather than the over-concretized interventions of the pharmacologists. In hypothyroidism, it is common for there to be an excess of adrenalin/noradrenalin, serotonin, histamine, and some of the pituitary hormones. Correcting thyroid function can immediately correct many problems, but especially when the energy deficiency has caused anatomical adjustments (redistribution of blood vessels and mast cells, for example) it's important to make the environment supportive in as many ways as possible.

In polycystic ovaries, menopausal symptoms, arthritis, angina pectoris, multiple sclerosis, some kinds of dementia, migraine, and emphysema, the relief achieved with a simple improvement of cellular energy can be rapid and complete. Presumably a similar process of biological reorganization is involved in the occasional spontaneous regression of tumors.

Although I don't think the autonomic nervous system, with its sympathetic and parasympathetic divisions, exists in the way it has traditionally been conceived, the idea can be useful if we think of using drugs and other factors in ways that tend to “quiet an overactive autonomic nervous system.”