Pathogenesis of vegetative crises

Vegetative crises are observed in a variety of diseases, both mental and somatic. This suggests that both the biological and the psychogenic mechanisms are involved in the pathogenesis of crises. Undoubtedly, in real life we are dealing with the constellation of these and other factors, with a greater or lesser specific gravity of each of them. However, for didactic purposes, it seems advisable to consider them separately, highlighting various aspects of the biological and mental.

Biological factors of the pathogenesis of vegetative crises

Violation of autonomic regulation as a factor in the pathogenesis of vegetative crises

Clinical practice and special studies convincingly show that vegetative kritichasche arise against sympathicotonia. Most authors play a decisive role in the emergence of crises prior to raising the sympathetic tone. Special studies have established that significant deviations in the vegetative tone toward sympathicotonia are characteristic of emotional disorders (fear, anxiety). As shown by clinical and physiological studies, the activity of the systems at the anatomical and functional level (sympathetic-parasympathetic), and on the functional-biological (ergo- and trophotropic) is synergistically organized and the nature of the vegetative manifestations at the periphery can be due only to the predominance of one of them. According to the theory of N. Selbach (1976), the relations between the two systems correspond to the principle of "swinging balance", i.e. An increase in tone in one system induces its increase in another. At the same time, the initially increased tone in one system entails a more significant deviation in the other, which displays the constantly existing fluctuations of vegetative homeostasis in the zone of increased lability. It is suggested that the pathogenicity is not so much the intensity of oscillations as the variability of physiological functions, their spontaneous changes. Clinical and experimental studies of patients with vegetative crises have revealed this lability in almost all systems: disturbances in the vibrational structure of the heart rhythm, a greater frequency of heart rhythm disturbances, changes in the diurnal rhythm of temperature, and perverted reactivity of vegetative systems in the sleep-wake cycle. This determines the instability of the system, increases vulnerability to external disturbances and disrupts natural adaptive processes.

Under such conditions, exogenous or endogenous stimuli can lead to a critical phase that occurs when all systems are synchronized, which is manifested by a vegetative crisis. It has been experimentally shown that the degree of behavioral and physiological activation is determined by the number of physiological systems participating in paroxysm. These data are in good agreement with clinical observations. Thus, the maximum intensity of the affective component (fear of death) is predominantly observed in the unfolded crisis, i.e. With the participation of many vegetative systems, and only in these crises the objective index of vegetative activation is steadily recorded-a significant increase in the pulse rate.

At the same time, the concept of activation can not be rigidly connected only with emotions of anxiety, fear. It is known that other emotional-affective states, such as anger, irritation, aggression, aversion or pathological forms of behavior are accompanied by physiological activation. Taking into account various clinical variants of vegetative crises (crises with aggression, irritation, "conversion crises", etc.), it is appropriate to assume that there is a general radical of vegetative regulation disorders that can be a common link in the pathogenesis of vegetative crises under different nosological forms.

Recently, there are concepts suggesting that in the emergence of some crises an essential role is played not so much by sympathicotonia, as by the insufficiency of the parasympathetic system. The basis for this assumption was the following facts:

1. frequent occurrence of crises during the period of relaxation;
2. registered in some patients with the help of monitoring a decrease in the pulse rate immediately before the development of the crisis;
3. a sudden increase in heart rate (from 66 to 100 or more per minute);
4. absence of the effect of beta-blockers in the prevention of a crisis provoked by the introduction of sodium lactate;
5. a slight decrease in adrenaline and norepinephrine in the urine in the pre-current period.

It is possible that different mechanisms of autonomic dysregulation are responsible for the development of crises in patients of different clinical groups.

Role of peripheral adrenergic mechanisms in the pathogenesis of vegetative crises

The most expressive manifestations of vegetative crises are symptoms of hyperactivity of the sympathetic nervous system, which can have a twofold origin: either an increase in the activity of sympathetic nerves, or an increase in the sensitivity of peripheral receptor formations (postsynaptic a and beta adrenoreceptors).

However, recent studies have not confirmed this hypothesis. Thus, in patients with vegetative crises, no greater content of noradrenaline and adrenaline or their metabolites was found than in healthy subjects. Moreover, a detailed study revealed a decreased sensitivity of adrenoreceptors in patients with vegetative crises. Given these facts, one can only assume that peripheral adrenergic structures are involved in the pathogenesis of crises, but the mechanisms for their participation remain unclear.

The role of central mechanisms in the pathogenesis of vegetative crises

Deployed vegetative crises with severe anxiety or fear, which are of a vital nature, can be considered as a variant of paroxysm of anxiety, fear with vegetative accompaniment. The subsequent anxious anticipation of the attack, the formation of secondary emotional and psychopathological syndromes lead to an adequate consideration of the pathogenesis of vegetative crises through the analysis of the cerebral mechanisms involved in the realization of normal and pathological anxiety.

Experimental data show that disturbance of central noradrenergic systems plays an important role in the mechanisms of anxiety. In animal experiments, it was shown that the large noradrenergic core of the brainstem, locus coeruleus (LC), is directly related to anxiety behavior.

Anatomically, LC through the ascending noradrenergic pathways is associated with the structures of the limbico-reticular complex (hippocampus, septum, tonsil, frontal cortex), and through descending - with the structures of the peripheral sympathetic nervous system.

Such a central arrangement with diffuse ascending and descending projections that pervade the entire brain makes the noradrenergic LC system a global mechanism potentially associated with the functions of alertness, arousal and anxiety.

The deepening of our understanding of the neurochemical mechanisms underlying VC is associated with the study of the properties of drugs, the mechanism of action of which is due to the activation or inhibition of LC. Thus, the administration of yohimbine (LC stimulant) to patients increased the frequency of crises and the report of patients on anxiety, which was accompanied by a greater than in healthy, isolation of 3-methoxy-4-hydroxyphenylglycol (MOGG), the main metabolite of cerebral norepinephrine. At the same time, administration of clonidine (a drug that reduces noradrenergic activity) to patients with vegetative crises led to a decrease in the plasma content of MOGG to a greater extent than in healthy subjects. These data indicate an increased sensitivity to both agonists and antagonists of central noradrenergic systems, which is confirmed by the violation of noradrenergic regulation in patients with vegetative crises.

Clinical observations of recent decades have convincingly shown that there is dissociation in the antiparoxysmal effect of typical benzodiazepines and antidepressants: if benzodiazepines are particularly effective immediately during the crisis, then the effect of antidepressants develops much more slowly and consists primarily in preventing recurrence of crises. These data suggested the participation of different neurochemical systems in the implementation of the crisis and its repeated initiations.

A special analysis of the long-term effect of tricyclic antidepressants (TA) showed that their anticrisis action is accompanied by a decrease in the functional activity of postsynaptic beta adrenoreceptors, a decrease in the activity of LC neurons, and a decrease in norepinephrine metabolism. These assumptions are confirmed by biochemical studies: thus, with prolonged exposure to TA, the decrease in MOFG in cerebrospinal fluid and in plasma, which correlates with a decrease in the clinical manifestations of the disease.

In recent years, along with noradrenergicheskim discussed the role of serotonergic mechanisms in the emergence of vegetative crises, which is due to:

1. the inhibitory effect of serotonergic neurons on the neuronal activity of those brain structures that are directly related to anxiety (LC, amygdala, hippocampus);
2. the effect of TA on the exchange of serotonin;
3. high efficiency zymeldin, which is a selective blocker of reuptake of serotonin in the treatment of crises with agoraphobia.

Taking into account the given data, the question arises of the possibility of the participation of different neurochemical mechanisms in the pathogenesis of vegetative crises, which may be due to the biological heterogeneity of crises.

Discussing the central mechanisms of pathogenesis of vegetative crises and emphasizing the important role of noradrenergic stem formations, one can not help but dwell on the significance of other structures of the limbic-reticular complex, in particular the parahippocampal region. The authors of clinical and experimental studies of recent years, investigating cerebral blood flow in patients with vegetative crises using positron emission tomography, found that in the intercreep period, patients have an asymmetric increase in cerebral blood flow, blood filling and oxygen utilization in the right para-hippocampal region.

Concrete evidence of involvement in the pathogenesis of vegetative crises in deep temporal region formations is in good agreement with recent reports on the high efficacy of anticonvulsants in the treatment of vegetative crises. It has been shown that antecapsin (clonazepam) has a good anticreeze effect. A model for the pathogenesis of vegetative crises was formulated in which parahyppocampal pathology determines the pathological sensitivity to anxiety states, and the triggering situation is the increase in the activity of noradrenergic projections to the hippocampal region (in particular, from the LC), which in turn realizes the vegetative crisis through the septo-amygdala complex .

Biochemical factors of the pathogenesis of vegetative-vascular crises

Traditionally, the emergence of vegetative crises is associated with the activation of the sympathetic nervous system, the humoral mediators of which are adrenaline and norepinephrine. In connection with this, it is of particular interest to study precisely these substances both at the time of the crisis and during the intercreeper period. When studying the content of catecholamines in the intercreeping period, there was no significant and steady increase in their increase in comparison with the control group. Moreover, according to OGCameron et al. (1987), in patients with vegetative crises under natural conditions, the content of epinephrine and norepinephrine in urine even slightly decreases. A number of studies have revealed a slight increase in adrenaline in the blood plasma just before the crisis is provoked. As for the crisis, both in spontaneous and in provoked vegetative crises, no single increase in either adrenaline or norepinephrine in blood plasma has been found.

Among other biochemical indicators, one can note a stable biochemical pattern reflecting respiratory alkalosis (increase in HCO3, pH, decrease in PCO2> calcium and phosphorus levels), which is detected in the intercreeper period and at the time of the crisis. In addition, the crises (both spontaneous and provoked) increase the level of prolactin, growth hormone and cortisol.

Thus, the biochemical pattern of vegetative crises consists in a certain increase in the level of prolactin, somatotropic hormone and cortisol, as well as in a complex of biochemical shifts reflecting respiratory alkalosis.

Investigations of lactate-induced crises have revealed a number of factors that can play a significant role in understanding the pathogenesis of crises. Thus, the following was established:

1. lactate infusion alone can cause significant physiological changes-an increase in heart rate, systolic blood pressure, lactate and pyruvate levels in the blood, an increase in HCO3 and prolactin levels, as well as a decrease in PcO2 and phosphorus concentrations in both healthy and patients;
2. the onset of the crisis coincides with the rapid and significant physiological changes following lactate administration;
3. There is a significant difference in the rate of increase in the level of lactate in the blood: in patients this index is significantly higher than in healthy individuals.

To explain the mechanism of lactate in provoking vegetative crises, several hypotheses are involved: stimulation of noradrenergic centers in the brain; hypersensitivity of central chemoreceptors; the role of cognitive-psychological factors.

Among the possible mechanisms of the crisogenic action of lactate, the role of carbon dioxide (CO2) is widely discussed today. Inhalations of 5% and 35% of CO2 are an alternative way of provoking vegetative crises in sensitive patients. At the same time, hyperventilation, in which the content of CO2 in the blood decreases and hypocapnia occurs, is directly related to autonomic crises, ie, two procedures that cause the opposite shifts of CO2 in the body lead to an identical clinical picture. How is this contradiction resolved and how is it related to the mechanisms of the crisogenic action of lactate?

It is known that an elevated level of cerebral CO2 is a strong stimulant of LC, while injected lactate, whose content in the blood of patients grows faster than in healthy people, being metabolized to CO2, contributes to a rapid increase in CO2 in the brain, which may occur, despite the general fall of PGO2 in the blood due to hyperventilation. It is assumed that the increase in brain CO2 is the common mechanism of the crisogenic action both when inhaled by CO2, and when lactate is administered.

It is more difficult to understand the role of hyperventilation in vegetative crises. In a study of 701 patients with chronic hyperventilation, vegetative crises were observed in only half of them. Hyperventilation may contribute to the onset of VC in some patients; it is unlikely that it is the principal cause of the attack in most patients.

A well-known attempt to combine the facts concerning the biochemical mechanisms of the pathogenesis of the vegetative crisis was the hypothesis of D. V. Carr, DV Sheehan (1984) who suggested that the primary defect is in the central chemoreceptor areas of the brainstem. In their opinion, in patients there is an increased sensitivity of these zones to abrupt changes in pH, arising with an increase in the ratio of lactate-pyruvate. With hyperventilation, developing hypocapnia leads to systemic alkalosis, which is accompanied by narrowing of the blood vessels of the brain and heart, and correspondingly, an increase in the ratio of lactate-pyruvate and the fall of intranieronal pH in medullary chemoreceptors. When sodium lactate is introduced, on the one hand, the medium becomes sharply alkaline due to sodium ions, ie, systemic alkalosis and corresponding changes in the brain occur; on the other hand, a sharp increase in lactate in the blood and cerebrospinal fluid leads to a rapid passive increase in the lactate-pyruvate ratio in the chemoregulatory zones of the trunk. Both ischemia and passive elevation of the lactate-pyruvate ratio decrease intracellular pH in medullary chemoreceptors with subsequent clinical manifestations of the vegetative crisis. This hypothesis also makes it possible to explain the mechanism of action of inhalation of CO2, since it has been shown in animal experiments that the pH on the surface of the brain decreases within a few minutes after the onset of inhalations of 5 % CO2.

Thus, probably in the presence of the initial alkalosis, any effects (sodium lactate administration, CO2 inhalation, hyperventilation, intrapsychic stress with ejection of catecholamines) increase the level of lactate more intensively than in healthy ones; this, in turn, causes a sharp change in pH on the surface of the brain and, as a consequence, anxiety and its vegetative manifestations.

Psychological factors of the pathogenesis of vegetative crises

A vegetative crisis can occur in almost any person, but this requires physical or emotional overload of extreme strength (natural disasters, catastrophes and other life-threatening situations); as a rule, such crises arise once. What factors cause the emergence of a vegetative crisis in ordinary life situations and what leads to their reappearance? Along with biological essential, and possibly leading, the role played by psychological factors.

As clinical practice shows, crises can occur in harmonic individuals with separate features of sensitivity, anxiety, demonstrativeness, propensity to subdepressive states. More often they arise in those patients, in whom these traits reach the degree of accentuation. The types of relevant personal accents and their characteristics are as follows.

Anxious-timid personality

In the anamnesis of these patients from childhood, there is a fear of death, loneliness, darkness, animals, etc. Often they have a fear of separation from their home, parents, perhaps on this basis, fear of the school, teachers, pioneer camps, etc., etc. For adult patients of this group are characterized by increased suspiciousness, a constant sense of anxiety, fears for one's own health, the health of close people (children, parents), hypertrophied responsibility for the task entrusted. Often excessive sensitivity (sensitivity) is of a diffuse nature: exciting events can be both pleasant and unpleasant; situations are real or abstract (movies, books, etc.).

At the part of patients leading are the features of anxious suspiciousness, timidity. In others, a sensitive accentuation comes first.

Dysthymic individuals

Dysthymic individuals with a more severe manifestation are subdepressive. Such patients are prone to a pessimistic assessment of events, focused on the sad aspects of life, often blame themselves in all negative situations. They react easily with reactive-depressive reactions; sometimes you can observe sharp mood swings.

Hysteroid individuals

They are characterized by pronounced self-centeredness, increased demands on others, pretentiousness, a tendency to dramatize ordinary situations, demonstrative behavior. Often, vivid demonstrativeness is masked by external hyperconformity. In the anamnesis, these patients often have somatic, vegetative and functional-neurological reactions in difficult life situations. As a rule, patients do not correlate these symptoms with the emotional tension of the situation. Clinically, these reactions can be manifested by short-term amauroses, aphonia, difficulty in breathing and swallowing due to a constant sensation of "coma in the throat", periodic weakness or numbness of the left arm, unsteadiness of the gait, acute pain in different parts of the body, etc. In clinical practice, however, it is rarely possible to observe pure variants of personal accentuations. As a rule, clinicians meet with more or less mixed variants, such as anxious-phobic, anxious-sensitive, anxious-depressive, hysterical-anxious, sensoro-hypochondriacal, etc. It is often possible to trace a hereditary predisposition to the manifestation of certain personal accentuations. Specially conducted studies have shown that anxious-phobic, dysthymic, anxious-depressive traits of character are often observed in close relatives of patients with vegetative-vascular crises, often they (especially in men) are masked by chronic alcoholism, which, according to many authors, is a certain way relief of alarm. Almost all researchers note an extremely high representation of alcoholism in relatives of patients with vegetative crises.

Identified personality characteristics of patients, on the one hand, are due to hereditary factors, but often they can arise or worsen under the influence of unfavorable situations of childhood - child psychogenies.

Conventionally, there are four types of child psychogenic situations that play a pathogenic role in the formation of personality traits.

1. Dramatic situations in childhood. These circumstances arise, as a rule, in families where one or both parents suffer from alcoholism, which generates violent conflicts in the family, often with dramatic situations (threats of murder, fights, the need for security to leave the house, and often at night, and t .). It is assumed that in these cases it becomes possible to fix fear by the type of imprinting (imprinting), which in the adult state, under the appropriate conditions, can suddenly manifest, accompanied by bright vegetative symptoms, i.e., to cause the appearance of the first vegetative crisis.
2. Emotional deprivation is possible in those families where the interests of parents are strictly related to work or other circumstances outside the family, while the child grows in conditions of emotional isolation with a formally preserved family. However, it is more often found in single-parent families, where a single mother does not develop emotional attachment to the child due to personal characteristics or situation, or care for him is limited to formal control over his studies, performance of additional lessons (music, foreign language, etc.). In such conditions, we are talking about the so-called insensitive control. Patients who have grown up in such a family are constantly experiencing an increased need for emotional contacts, and their tolerance to stress is significantly reduced.
3. Super-anxious, or hyperprotective, behavior. In these families, excessive anxiety as a trait of the parent or parents determines the upbringing of the child. This is an excessive concern for his health, education, anxiety in every uncertain situation, constant expectation of danger, unhappiness, etc. All this often forms excessive personal anxiety in the patient as a variant of trained behavior. Undoubtedly, in these cases hereditary predisposition to an alarming stereotype is transmitted.
4. Constant conflict situation in the family. Conflict situation, arising for various reasons (psychological incompatibility of parents, difficult material and living conditions, etc.), creates a constant emotional instability in the family. In these circumstances, a child emotionally involved in a conflict can not effectively influence him, he is convinced of the uselessness of his efforts, he is feeling helpless. It is believed that in such cases, so-called trained helplessness can be formed. In later life under certain difficult situations, the patient based on past experience builds the forecast that the situation is not solvable and helplessness occurs, which also reduces tolerance for stress.

Analysis of children's family situations is extremely important for every patient with autonomic crises, as it significantly complements our understanding of the mechanisms of crises formation.

Turning to the analysis of actual psychogenies, i.e. Those psychotraumatic situations that immediately preceded the emergence of crises, you must immediately distinguish 2 classes of psychogeny - stress and conflict. The interrelationships between these factors are ambiguous. So, intrapsychic conflict is always a stress for the patient, but not every stress is caused by conflict.

Stress as a factor causing crises is now being widely studied. It has been established that both negative and positive events can lead to a stressful effect. The most pathogenic in terms of overall morbidity were severe bereavement - the death of the spouse, the death of the child, divorce, etc., but a large number of various events that occurred in a relatively short period of time (expressed in terms of psychosocial stress) may have the same pathogenic effect, as well as a heavy loss.

It was found that before the debut of vegetative crises, the overall frequency of life events increased significantly, and mostly these are events that cause distress. It is characteristic that a large loss is less associated with the appearance of VC, but significantly affects the development of secondary depression. For the emergence of the same vegetative crisis, the situation of threat is more important - a real threat of loss, divorce, a child's disease, iatrogenia, etc. Or an imaginary threat. In the latter case, the peculiarities of the personality of patients acquire special significance. Some authors believe that these features play a leading role because of increased anxiety, a constant foreboding of danger, and in addition, increased stress due to a subjective sense of inability to cope with it (trained helplessness). At the same time, a high level of psychosocial stress reduces the effectiveness of protective mechanisms for overcoming stress.

Thus, the intensity of stress, its specific characteristics in combination with personality characteristics play an important role in the emergence of vegetative-vascular crises.

If there is a conflict, an external stress event; can determine the culmination of the conflict, which, in turn, can lead to the manifestation of the vegetative crisis. Among typical conflicts, we should note the conflict between the intensity of motivations (including sexual ones) and social norms, aggression and social demands, the need for close emotional ties and the inability to educate them, etc. In these cases, the ongoing conflict is the soil that when exposed to additional nonspecific stress, can lead to the manifestation of the disease in the form of a vegetative crisis.

Discussing the psychological factors of the emergence of a vegetative crisis, one can not ignore cognitive mechanisms. There are experimental data explaining the emotional-affective component of the crisis as secondary to the primary peripheral changes:

1. it turned out that the presence of a doctor could prevent the usual fear arising from the pharmacological modeling of the crisis;
2. using repeated lactate infusions in the presence of a physician, it was possible to conduct an effective desensitizing treatment of patients with crises;
3. the data of individual authors indicate that, using only psychotherapy without the influence of medications, it is possible to block the appearance of lactate-induced crises.

Highlighting the cognitive factors involved in the formation of the vegetative crisis, it is necessary to emphasize the main ones: memory for past experience; anticipation and apprehension of a dangerous situation; assessment of the external situation and bodily sensations; feelings of helplessness, uncertainty, threats and loss of control over the situation.

Combining the psychological and physiological components of the pathogenesis of the vegetative crisis, several models of their occurrence can be proposed.

1. Stress → alarm → vegetative activation → crisis.
2. Stress → anxiety → hyperventilation → autonomic activation → crisis.
3. The situation of the culmination of intrapsychic conflict → anxiety → autonomic activation → crisis.
4. The situation of reviving early (child) patterns of fear → vegetative activation → crisis.

In all four models, the overgrowth of vegetative activation in the vegetative crisis occurs with the participation of cognitive factors.

However, the issues of correlation, primary and secondary psychological and physiological components in the formation of crises require further research.

Thus, it is necessary to emphasize that vegetative crises can develop in individuals with certain personality traits, genetically incorporated and / or conditioned by psychogenic influences of the childhood period, with a high level of psychosocial stress or at the culmination (aggravation) of the intropsychic conflict.

The primacy of physiological changes and the secondary nature of their perception by the individual with the formation of the emotional-affective component remain primary, or affect is accompanied by bright vegetative symptoms, determining the clinical picture of the vegetative crisis.

[1], [2], [3], [4], [5], [6], [7], [8]