Sustainable Nutrition the Impact of Food Consumption

Introduction

Climate change is an important challenge in the latest century. Carbon emission is the cause of climate change, which is made by the life activity of people [1]. Global warming is increasing each passing day, affect to food harvesting, production, processing, and consumption. Food production imbalance should be a cause of energy and nutrient deficiency. According to UNICEF, climate change is an important factor in increasing maternal and child nutrition malnutrition [2-4]. Although the United Nations (UN) Framework Convention on Climate Change (1992) was accepted within the scope of combating climate change, international consensus could not be reached in preventing environmental disasters. At the Paris Climate Conference, 196 states agreed to limit global warming to 2°C [4]. In this review article, the effects of sustainable food consumption on health and the environment are presented based on current literature.

Environmental Effects of Nutrition

Efficient use of natural resources and environmental concerns have been in dietary guidelines since the 1980s [5]. Food is considered one of the biggest health and environmental problems of the 21st century, which is in the Anthropocene age. Sustainable development goals were affected by food production systems [6]. Sufficient nutrition for the world population needs special effort without harming the environment and destroying natural resources. Food waste is the other problem for sustainable nutrition in addition to sustainable production systems [3,4]. Nowadays, more than 820 million people are malnütre, 2 billion people have micronutrient deficiencies, but on the other hand, more than 2 billion people are dealing with health problems caused by obesity [6,7]. At this point, sustainable nutrition systems have more attention [7]. 48% of fertile agricultural land and 70% of clean water are used for global food production. Limited natural resources and greenhouse gas emissions (responsible for 20-35%) as a result of production/ consumption increase the need for a sustainable food system [8,9]. Among the environmental problems caused by the existing food systems; there are factors such as water and food losses/wastes during processing/packaging/transport and fossil fuel use. The environmental impact of meat and dairy products is the highest [8]. According to a study conducted in 2016, red meat production is 568% of the global need [10].

In addition, excessive consumption of animal foods causes intake the high amount of saturated fat, cholesterol, and salt, they increase the risk of cardiovascular disease, cancer, stroke, obesity, and death in humans [8]. Diseases that can be transmitted from animals and meat and antibiotic drugs used in treatment also negatively affect health [11]. In a study conducted in 2018, in the analysis of plant foods, dietary modeling has been found to reduce premature deaths by 12% and greenhouse gas emissions by 84% instead of animal foods modeling [12]. Today, although there are studies that analyze the impact of agricultural production on sustainability in terms of nutrition, health and the environment, it needs to be supported by studies and evidence on the effects of agricultural products such as global climate change, water scarcity, micronutrient deficiencies [13,14]. Reliable studies should be conducted to evaluate the sustainability of methods such as sustainable aquaculture farms, regenerative agriculture and alternative foods such as cultured meat and insects that are likely to be implemented in the future. Multidisciplinary and scientific studies are needed to reduce the negative effects of the agricultural food production system on food safety and sustainability [15].

Sustainable Diets

In the “Guidelines for Sustainable, Healthy Eating Principles” published by FAO (Food and Agriculture Organization) and WHO (World Health Organization) in 2019, it is stated that many people in the world do not have access to safe, affordable, and healthy diets, and one out of three people suffers from hunger, stunting, overnutrition, micronutrient deficiencies, overweight/obesity. It has been reported that people experience nutritional problems such as non-communicable diseases [9]. Healthy nutrition is expected to be provided by increasing plant foods in the diet and reducing animal foods, saturated fats, processed foods, and added sugar. For this expectation to be realized by 2050, the consumption of foods such as red meat and sugar should be reduced by 50% globally and the consumption of fruits, vegetables, legumes, and oilseeds should be increased by 100%. Global implementation of dietary changes is thought to prevent approximately 10.8- 11.6 million deaths per year [7]. There are three principles were mentioned in creating a healthy and sustainable diet. Firstly, nonessential nutrients, highly processed, and high-energy ingredients of food consumption should be decreased. Secondly, plant-based foods should be recommended compared to animal foods. The third principle is sufficient energy intake of people, not-low and not-excessive. Balance of energy intake protects environmental energy use and decreases greenhouse gas emissions [16]. The unprocessed, local and seasonal plant-based diet is closer to sustainability [17]. Another study stated that a sustainable diet should meet health, economic and social justice, clean air/water/ soil and enjoyable food culture [18]. Mediterranean diet and the New Nordic diet are advantaged in terms of having the lowest environmental effects according to healthy diets including animal foods [5,9]. In a meta-analyzed in which 63 studies were examined, it was stated that the sustainability was more in the vegetarian diet and the diets containing a small number of animal foods [11]. Vegan and vegetarian diets have lower effects on the environment [5]. In a review study, when the dimensions of diets such as the low impact on greenhouse gas emissions, reduction in total death rates, and less land use in production were evaluated; vegetarian, pescetarian, Mediterranean diet, omnivorous diets [11].

Results and Conclusion

Sustainable agriculture studies showed that the methods applied today do not use natural resources efficiently, they have negative effects on the environment. Sustainable diets such as the Mediterranean Diet and the New Nordic Diet benefit global health and the environment through their ingredients and the way food is produced. Multidisciplinary studies and projects are required for the implementation of sustainable food production/consumption.

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Primary Non-Degenerative Dysautonomy from the Point of View of the Otorhinolaryngologist

Introduction

Non-degenerative primary dysautonomia is a pathology with a physiology of integration of inaccurate responses between the central nervous system and the autonomic nervous system, frequent in the population of all ages worldwide, unfortunately with a lack of precise prevalence numbers since it presents with a variety of signs and symptoms that are sometimes vague, unspecific and confusing (dizziness, syncope, paresthesias, dyspnea, insomnia, palpitations, constipation-diarrhea, fatigue, headache, sweating, mood changes, chest tightness), which means that it is not fully addressed, being fragmented by different medical specialties and from the health area: otorhinolaryngologists, cardiologists, endocrinologists, gastroenterologists, neurologists, pediatricians, pulmonologists, psychiatrists, internists and without forgetting nutritionists, all of this directly affects the delay in diagnosis, non-specific therapy and poor prognosis with the development of comorbidities, causing frustration, stress, and negative impact on the quality of patient’s lives.

Theoretical Framework

Generalities

A. Definition

During the bibliographic review, different definitions were evidenced, but the majority agreed that it is a pathology where inaccurate of compensatory responses are presented from the central regulatory centers (bulbar vasomotor centers and superior nervous centers controlling the vasomotor center), towards the autonomic nervous system [1].

B. Terms and Nomenclature with which it is Cited in the Literature

As mentioned above and it became clear during the literature review, primary non-degenerative dysautonomia has been labeled under different terms such as: vertiginous syndrome, migraine, irritable bowel syndrome, gallbladder dyskinesia, fibromyalgia, chronic fatigue syndrome, anemia syndrome, hypoglycemia, irritable bladder, mitral valve prolapse syndrome, orthostatic hypotension, [2,3] among many others, resulting in confusing conceptualization, since the nomenclature is frequently selected based on the predominant symptomatology at the time of diagnosis of the disease patient, without thinking of a comprehensive approach to pathology. In relation to the synonyms used and with which the pathology is frequently confused, we have vertigo, which always refers to an alteration of the vestibular system (housed in the inner ear and whose neurological center is in the brainstem), while the dizziness is a balance disorder not always related to it, within the vertiginous pathology of the Otorhinolaryngology area, Benign Paroxysmal Postural Vertigo, is a common pathology, where in 50% or more of the cases no etiology is found, so we could consider being facing Dysautonomia [4] The pathology is also labeled as migraine, which is a chronic disorder of the nervous system, characterized by the appearance of typical and recurrent episodes of headache, which are usually associated with nausea, vomiting, photophobia and sonophobia [5].

We will also mention irritable bowel syndrome, currently defined based on the modified Rome criteria, as the manifestation of abdominal discomfort or pain for at least 12 weeks (not necessarily consecutive) in the last 12 months, which cannot be explained due to structural or biochemical abnormalities, and having at least two of the following three characteristics: the pain ceases after defecation, its onset is associated with a change in the frequency of bowel movements or a change in the defecation form [6]. For its part, we know that gallbladder dyskinesia corresponds to a gallbladder motility disorder, which manifests clinically with nausea, vomiting or both, pain in the right upper quadrant that can radiate to the right intrascapular region. This disease is diagnosed with a gallbladder scintigraphy [7] and is also confused with dysautonomia. Regarding fibromyalgia, considered a synonym for several symptoms in common, we will mention that it is a syndrome characterized by diffuse, chronic musculoskeletal pain, of nonarticular origin, which is usually accompanied by insomnia, fatigue, morning stiffness and cognitive alterations, with a neurobiological pathophysiology [8].

Chronic Fatigue Syndrome has often been used synonymously and is clinically distinguished by persistent or recurrent debilitating fatigue for more than six months in the absence of any other identifiable medical cause. From 40 to 90% of patients with chronic fatigue syndrome report syncope or dizziness and symptoms of orthostatic intolerance such as disabling fatigue, dizziness, decreased concentration, tremor and nausea [9]. For its part, we know that the anemic syndrome refers to the decrease in hemoglobin content or the number of red blood cells due to blood loss or to the alteration in the production or destruction of the erythrocytes themselves. The clinical expression of this syndrome is the result of tissue hypoxia and its specific signs and symptoms represent compensatory cardiovascular responses depending on the severity and duration of hypoxia [10]. With regard to hypoglycemia, the most correct definition corresponds to the presence of neuroglycopenic or adrenocholinergic symptoms coinciding with low capillary or plasma glucose (around 50 mg/dl) and disappearance of symptoms when blood glucose increases, which causes symptoms as diverse as tachycardia, palpitations, tremors, paleness, anxiety, sweating, nausea, hunger, dizziness, headache, weakness, blurred vision, decreased ability to concentrate, confusion, decreased level of consciousness, diplopia, seizures, behavioral disturbance, aggressiveness, incoherent conversation, delirium, among others [11]. As we can see, many of these symptoms coincide with those of Dysautonomia, but the pathophysiology is totally different. Irritable bladder, also considered a synonym, was defined in 2002 by the International Continence Society as an overactive or irritable bladder syndrome, characterized by the presence of micturition urgency alone or in combination with other symptoms, such as urge incontinence, generally associated to an increase in micturition frequency and nocturia, in the absence of other demonstrable disease, therefore it is considered a syndrome with symptoms corresponding to the filling of the lower urinary tract [12].

If we define mitral valve prolapse as the herniation of one or both mitral leaflets, usually the posterior one, into the left atrium during systole, causing frequent symptoms such as fatigue, palpitations, dyspnea, and nonspecific chest pain [13], that coincide with those presented by patients with Dysautonomia, we can understand, because these pathologies are often considered synonymous. In relation to orthostatic hypotension, whose definition corresponds to a decrease in systolic blood pressure of 20 mm Hg or diastolic blood pressure of 10 mm Hg, during the passage to the standing position, and with frequent association of arterial hypertension, we can understand why It is often considered synonymous with Dysautonomia, but the big difference is that in the second there is no history of arterial hypertension [14]. From the above, we can evidence the coincidence of Dysautonomia symptoms with those of different pathologies, but with a totally different pathophysiological origin, which explains the confusion and misdiagnosis from the initial stages.

C. Classification

Dysautonomia’s are classified according to the etiology, the deficient neurotransmitter or the anatomical distribution of the affected neurons (Table 1).

Table 1: Classification of Dysautonomies.

1) Etiological Classification

Primary and secondary dysautonomia.

a) Primary of unknown etiology or idiopathic: characteristically, central or peripheral autonomic neurons, or both, exhibit imprecise compensatory responses from central regulatory centers to the autonomic nervous system without apparent cause, where central autonomic neurons, peripheral autonomic neurons, or both can even degenerate or die, for example, as in Parkinson’s disease.

b) Secondary: when it is the result of a disease that affects the autonomic fibers secondarily, for example, in diabetes or amyloidosis.

2) Neurochemical Classification

Cholinergic, adrenergic and mixed dysautonomia.

a) Cholinergic: Acetylcholine is the deficient neurotransmitter. Acetylcholine was one of the first neurotransmitters characterized both in the peripheral nervous system and in the central nervous system only in mammals, and participates in the regulation of various functions such as: activation phenomena of the cerebral cortex, the circadian cycle, memory, association, and higher-order thinking, among others. It is synthesized from choline, which is a dietary quaternary amine important for cell membrane integrity, neurotransmission, signaling, intracellular transport and lipid metabolism. Foods rich in choline, in addition to eggs, are liver, soybeans, meat, milk and peanuts. Acetyl - CoA also participates in the formation of acetylcholine, being a crucial intermediate molecule for various metabolic pathways of both lipids and proteins and carbohydrates. Its main functions include transferring the acetyl group to the Krebs cycle and it participates in the synthesis of acetylcholine, through a reaction catalyzed by choline acetyltransferase. There are mechanisms that precisely regulate the synthesis and release of acetylcholine, which acts on two types of receptors: ionotropic (nicotinic) and metabotropic (muscarinic) coupled to G proteins. Muscarinic receptors: M1, M2 and M3 are involved with the production of the second messenger cAMP. The M2 and M4 receptors inhibit the formation of cAMP, activate K+ channels and reduce Ca++ ion entry through voltagedependent channels, effects mediated by G proteins (Gαi and Gαo) [15]. Acetylcholine receptors are widely distributed in various areas of the central and peripheral nervous system and are responsible for the various physiological actions of acetylcholine. Its study has generated great interest, because various alterations in cholinergic transmission have been related, directly or indirectly, to severe disorders such as Alzheimer’s and Parkinson’s disease.

b) Adrenergic: Amines are the deficit neurotransmitter. Amines or catecholamines are a group of compounds that have the catechol group in their chemical structure , among the most important are adrenaline, noradrenaline and dopamine. They are synthesized from tyrosine, this amino acid can be derived directly from the diet or be synthesized in the liver from the amino acid phenylalanine. Foods rich in tyrosine are for example: meat, fish, dairy, eggs, vegetables, legumes, brown rice, seeds, whole grains, apples, asparagus, avocados, carrots, romaine lettuce, spinach, soy products, watermelon, cucumber, parsley, watercress, among others. Tyrosine enters chromaffin cells (or neurons if we are talking about the nervous system) through active transport. Adrenaline or epinephrine is synthesized and stored in the adrenal medulla and also in peripheral sympathetic nerves and released into the systemic circulation. Dopamine is found in the adrenal medulla and peripheral sympathetic nerves, but it acts primarily as a neurotransmitter in the central nervous system. Catecholamines participate in the integration mechanisms of both the central nervous system and the endocrine system. Therefore, the sympathetic nervous system and the adrenal medulla make up an anatomical and physiological unit, known as the sympathoadrenal system. This system plays a fundamental role, together with the hypothalamic-pituitaryadrenal axis, in responses to stress or injury [16].

c) Mixed when cholinergic, adrenergic, serotonergic are imprecise neurotransmissions [17,18]. Serotonin is a neurotransmitter with very important functions at the neuronal level, it regulates mood and behavior, prevents depression, anxiety and intervenes in sleep disorders. Low serotonin levels have been associated with hyperalgesia, aggression, depression and anxiety, and even the development of migraines, because when serotonin levels drop, blood vessels dilate. It is formed from tryptophan, an amino acid contained in eggs, milk, fish, meat and whole grains [19].

3) Anatomical Classification

Central and peripheral dysautonomia.

According to the anatomical distribution of the affected neurons.

a) Central: The affected neurons are preganglionic.

b) Peripheral: The affected neurons are ganglionic or postganglionic. It is worth mentioning that the cell body of the preganglionic neurons of both the sympathetic and parasympathetic divisions of the autonomic nervous system is located in the central nervous system (spinal cord or brain stem), and its axons synapse with the postganglionic neurons of the autonomic ganglia. These postganglionic neurons are autonomic nerve fibers from the ganglion to the effector organ (Table 2). In the previous table, a summary of the three classifications of Dysautonomies previously presented is presented.

Table 2: Synthesis of the activity of the sympathetic and parasympathetic nervous system in different anatomical regions [46].

D. Epidemiology

Dysautonomia are reported worldwide, whose most common symptoms are tachycardia, dizziness, syncope, weakness or fatigue, cognitive difficulty and blurred vision, presenting at any age [20]. In relation to syncope, which is only one of the multiple signs and symptoms of the disease, it is mentioned worldwide that approximately 37% of people suffer from it at least once in their life and 10% of adults present them recurrently, it is believed to be responsible for 3% of hospitalizations and 6% of visits to the emergency department, presenting more frequently in young women than in men. Most reports focus on relatively select populations such as the military, senior care facilities, or primary care outpatient clinics. For example, follow-up of 3,000 US Armed Forces individuals (mean age 29 years) revealed that 27% had experienced a syncopal episode during their lifetime. Extrapolation of these findings to medical practice is limited not only by the nature of the setting in which the research was conducted, but also by the variable manner in which symptoms were assessed [21]. If we add to the previous statistics the variety of symptoms that the disease, we can dimension the pathology. Dysautonomia is common at all ages, as seen in medical consultation, in Mexico it is estimated that it affects 10% of the teenagers. If we refer to epidemiology in relation to the prevalence of syndromes, is displayed:

a) Chronic Fatigue Syndrome: This syndrome is clinically distinguished for persistent or recurrent debilitating fatigue for more than six months in the absence of any other identifiable medical cause. From 40 to 90% of patients with chronic fatigue syndrome report syncope or dizziness, and symptoms of orthostatic intolerance such as disabling fatigue, dizziness, decreased concentration, tremor and nausea [9]. Irritable bowel syndrome: currently defined based on the modified rome criteria, as the manifestation of abdominal discomfort or pain for at least 12 weeks (not necessarily consecutive) in the last 12 months, which cannot be explained by structural abnormalities or biochemical, and having at least two of the following three characteristics: the pain ceases after defecation, its onset is associated with a change in the frequency of bowel movements or a change in the form of bowel movements [6]. In Mexico, it is reported that 93% of patients affected by the syndrome are women and although there are no adequate epidemiological studies, it was determined that the syndrome has an approximate prevalence of 16 to 21% among the population. The age of onset can vary from 17 to 53 years [22,23]. Benign paroxysmal positional vertigo is the most common entity within vertigo of peripheral origin. It is characterized by attacks of vertigo triggered by positional changes of the head and of short duration. It usually occurs in people over 40-50 years of age, and up to 50% of cases are not due to a known cause, which is why it is called idiopathic benign paroxysmal positional vertigo [4].

Physiology and Pathophysiology

Physiology of the Autonomic Nervous System: The autonomic or vegetative nervous system is an important component of the nervous system, made up of a complex set of neurons and nerve pathways that control the function of the different visceral systems of the body. Its global function is to maintain the state of homeostasis of the organism and carry out adaptation responses to changes in the external and internal environment. It is made up of three efferent components sympathetic, parasympathetic and enteric– innervates the heart muscle, the smooth muscle of all organs and the exocrine and endocrine glands. Thus, it regulates respiration, circulation, digestion, metabolism, glandular secretion, body temperature, reproduction and, in addition, coordinates all these vital functions to maintain body homeostasis (Table 2). It is not subject to voluntary or conscious control. The sympathetic nervous system plays a fundamental role in the integrity of the organism, since in a very fast and effective way, it emits a response to external stimuli that can threaten the integrity of the individual and for its part the parasympathetic function is oriented, contrary to that of the sympathetic, to the conservation of energy and system reset. The table above shows the participation of the two main branches of the autonomic nervous system and their influence on different anatomical regions. For example, normally 25% of the circulating blood volume is in the chest; once the upright position is assumed, gravity produces a sudden downward movement of 500 ml of blood towards the abdomen and lower limbs; approximately 50% of this volume is redistributed in the following seconds. This causes a decrease in venous return to the heart and in cardiac filling pressures, which can lead to a decrease in stroke volume by 40% [24] and in a normal subject, orthostatic stabilization is obtained in a minute or less after standing up, thanks to the correct compensation of the autonomic nervous system, since the high pressure mechanoreceptors located in the carotid sinus and the aortic arch are activated, as well as the low pressure ones located in the heart and lungs [25]. Early adaptations to taking the upright position result in an increase in heart rate of 10 to 15 beats per minute and diastolic pressure of 10 mm Hg, with little or no change in systolic pressure [26]. The inability of any of these processes to function properly or in a coordinated manner results in a failure in the normal response to sudden postural changes, which generates hypotension, elements that may be sufficient to produce cerebral hypoperfusion, hypoxia, and loss of consciousness. Autonomic nervous system dysfunctions involve multiple and variable clinical manifestations, which are often underestimated in clinical practice. However, they must always be taken into account due to their diagnostic implication, due to their impact on the patient’s quality of life and due to their prognostic influence on life expectancy [27]. Therefore, the sympathetic function plays a fundamental role in the preservation of the organism, since it quickly and very effectively causes a response to external stimuli that may threaten the integrity of the individual and, for its part, the activation of the parasympathetic system is oriented, contrary to that of the sympathetic, to the conservation of energy. This fascinating and complex interrelation can be summarized below, with regard to primary non-degenerative dysautonomia.

Pathophysiology of Primary Non-Degenerative Dysautonomia: The vasomotor center is located in the brain stem, and it sends fibers to the spinal cord and blood vessels. Within the superior nervous control centers of the vasomotor center, is the motor cortex, which through integration through fibers to the hypothalamus, participates in an important way in the regulation that includes from environmental stimuli to emotional stimuli [28]. In this pathology, we find imprecise compensating responses from the central regulatory centers (bulbar vasomotor centers and superior nervous centers controlling the vasomotor center), towards the autonomic nervous system. Also, as pointed out by Cadman [17] and the psychiatry group of Warnock and Clayton [18], serotonin could play a very important role at the central level as the origin of these disorders, by causing a state of sympathetic hyperreactivity with hypo reactivity to the phenomena of stress. In general, diseases that affect the autonomic nervous system produce symptoms due to its hypoactivity or insufficiency; less frequently there are diseases that cause hyperactivity.

Natural History of Non-Degenerative Primary Dysautonomia: The pathophysiological study and clinical characterization of dysautonomia syndromes that manifest with orthostatic intolerance have been a challenge for researchers in all areas due to their frequent presentation and the lack of therapeutic tools that allow their adequate management, this context, invariably has repercussions on the knowledge of the natural history of the disease, since we remember that hypotension and dizziness as symptoms of orthostatic intolerance, only constitute part of the symptomatology of primary non-degenerative Dysautonomia, so the conceptualization of the natural history of the disease pathology globally speaking, it is also divided [29]. For example, the mortality rate is known to be increased among persons with syncope secondary to age-related orthostatic hypotension and concomitant conditions [30]. Derived from hypotension, syncope, dizziness and fatigue, patients have a tendency to suffer falls and accidents, with the presentation ranging from simple injuries, through fractures, severe head injuries and even death. In relation to gastrointestinal symptoms, patients present anorexia, and weight loss with a tendency to malnutrition, coupled with muscle pain and paresthesias, especially in the lower limbs, immobility is triggered, with the development of frustration, social isolation, depression, anxiety and behavioral alterations with development of comorbidities.

Clinical Manifestations and Diagnostic Criteria

Clinical Manifestations: The symptoms and signs are very varied and involve many organs and systems, which makes diagnosis difficult, and they can also overlap with each other. Among the most common we find (Table 3) as shown in the table above, the symptomatology involves several apparatuses and systems innervated by the autonomic nervous system, and added to the characteristic dysregulation, patients can be found in the spectrum of excess and/or deficit of innervation, usually deficit, what produces the polarity and alternation of the symptomatology. All these signs and symptoms are not standardized, there are no clinical practice guidelines for management, and treatment and consultations with other specialties are offered in relation to the findings in the clinical history and physical examination, usually at the time of diagnosis in based on the experience and individual criteria of the treating physician, often without carrying out a deep comprehensive approach and without taking into account the quality of life of the patient [14,31]. The symptoms can be triggered by different situations of daily life such as (Table 4). All the aforementioned triggers precipitate the symptomatology in proportion to the compensatory and homeostatic capacity of each patient and to the imprecise responses of the autonomic nervous system according to the course of the disease at a specific moment of the pathology [32]. We must mention the importance of the splanchnic circulation, which is the part of the systemic circulation that irrigates the abdominal portion of the digestive tube, as well as the spleen, pancreas, and liver.

Table 3: Main symptoms and signs of Dysautonomia [2,21,47,48].

Table 4: Frequent triggers of Dysautonomia [2,30].

It is the largest regional circulation arising from the aorta and receives more than a quarter of the left ventricular output during rest, regardless of whether the subject is freshly fed or not. This volume, for example, is equivalent to about ten times the blood flow received by the entire skeletal muscle mass at rest, an enormous figure if one takes into account that this mass has the largest vascular bed in the human body. This large size determines that the splanchnic circulation is the most important reservoir of blood in the entire body. Thus, when the systemic blood pressure tends to decrease for any reason, intestinal vasoconstriction will displace about a fifth of the blood volume towards the vital organs that require it. The most powerful stimulus to increase intestinal blood flow is the ingestion of food, so that the intestinal metabolic activity is multiplied to digest and absorb. The entry of chyme into the intestinal lumen increases, to a greater or lesser degree, the blood flow to the mucosa, depending on the type of constituents of that content and the amount. For example, in the jejunum, blood flow increases about 10 times more if it receives digested food mixed with bile compared with only bile or only amino acids. This has an important implication in the dietary recommendations as part of the initial treatment, suggesting a diet with a low carbohydrate content, in fractions and avoiding large meals [33-36].

Diagnostic Criteria: As is done with all patients, it begins with a complete clinical history, emphasizing the relevant history and the precise semiology of the symptoms. A detailed clinical history, with an adequate physical examination, and special attention in the cardiovascular and neurological areas, are invaluable for the diagnostic scope, overcoming the indiscriminate request for multiple tests. It is important to always identify any drug that the patient is taking, including non-allopathic drugs. When a young subject presents with symptoms of autonomic dysfunction, the possibility of illicit drug or alcohol abuse should be considered within the differential diagnoses. Diagnostic tests should be requested in a directed manner and determined by the findings, if necessary, laboratory tests such as complete blood count, blood chemistry, thyroid function tests, various hormonal profiles, general urine test, immunological profile, and tests cabinet that may include ultrasound, electrocardiogram, cardiac holter, echocardiogram, electroencephalogram, brain imaging studies such as tomography or magnetic resonance, in order to rule out other pathologies, integrate the probable diagnosis or diagnoses and stage them, to request consultations with other specialties, if necessary. A drop in systolic pressure of more than 20mm Hg or a drop of more than 10 mm Hg in diastolic pressure during the two minutes following standing after lying down is highly suggestive for the diagnosis, without the presence of reflex tachycardia [21,27,28]. If a negative diagnostic test is obtained and other organic alterations are ruled out, with the previously mentioned studies, the psychiatric evaluation can finally be carried out, because, as no organic alteration is found that justifies the patient’s symptoms after having carried out a complete study, specialized assessment is requested for the study of other types of pathologies with a mental and/or psychiatric context, which is not mentioned in this thesis, since it is not part of the stated objectives, as it corresponds to completely different topics.

Treatment

Therapeutic Options: Within the therapeutic options, we find general measures, diet, pharmacology and surgical treatments, according to the judgment and experience of the initial treating physician. The most commonly prescribed non-pharmacological measures are listed below [22,23] .

General measures:

i. Avoid prolonged standing.

ii. Avoid inactivity.

iii. Ambulation at a moderate pace.

iv. In a sitting position, avoid immobility for a long time.

v. Avoid extreme and sudden temperature changes (steams, saunas).

vi. Use of compressive elastic socks.

vii. Moderate aerobic exercise, as it improves venous return.

viii. Avoid high altitude cities, mountains, height and speed rides.

ix. Alterations in fluids and blood corrected as soon as possible.

x. Avoid sleeplessness, stress and Valsalva maneuvers.

xi. Sleep with the head of the bed raised (between 15 and 30cm).

xii. Use of stockings with elastic support (controlled pressure of 30 to 40mm Hg)

a) Pharmacology

Depending on the evolution, pharmacological treatment is suggested [22,23,29]:

i. Increase blood volume with the use of mineralocorticoids (Fluodrocortisone).

ii. Increase vasoconstriction with alpha agonists (Midodrine, Clonidine).

iii. Block the effect of norepinephrine with beta blockers (Propanolol, Metoprolol, Nadolol, Pindolol).

iv. The use of anxiolytics and antidepressants is sometimes necessary (Citalopram).

v. Selective serotonin reuptake inhibitors (Fluoxetine, Sertraline).

vi. Synthetic amino acid that is decarboxylated to norepinephrine without passing through the enzyme dopamine beta hydroxylase (Dihydroxyphenylserine) [37].

An interesting finding in a good number of patients with autonomic failure is the presence of anemia. In a study by Hoeldtke and Streeten , it was shown that subcutaneous injections of erythropoietin, in addition to raising cell counts, dramatically increased blood pressure [38].

b) Surgical Treatment

Pacemaker, which would only be indicated exceptionally for the management of recurrent syncope that does not respond to previous therapies. From the point of view of psychology, they propose adding to these patients, in order to provide a more comprehensive treatment, the work of emotional self-knowledge through integrative psychotherapy, and thus provide the patient with the tools to detect stress factors and their correct treatment management, promoting experiences that promote well-being, establishing as a priority the management of techniques that help identify negative emotions and address them in the best way [28].

Dietary Treatment

A diet is suggested that includes [39-44] :

i. Avoid dehydration, drink 2 to 3 liters of water a day until you achieve clear and diluted urine.

ii. Avoid copious meals.

iii. Rest 15 to 30 minutes after meals.

iv. Increase salt in meals; If there are no contraindications, 6 grams per day is recommended (place 2 level teaspoons of coffee in a salt shaker and add it to food daily).

v. Avoid alcohol.

vi. Three main fragmented meals and two intermediate snacks.

vii. Diet with carbohydrates that do not exceed 45% of the daily caloric intake [45-48].

Prognosis

There are no clinical, treatment, or prognostic pathology practice guidelines reported. As evidenced so far, the prognosis for these patients is generally good for life but guarded for function. Several daily syncopal episodes may occur, with frequent falls, exercise limitation and even mobility and independence, significantly affecting the prognosis, producing from complete recovery to a chronic debilitating course with significant residual effects. Diaphoresis and bowel and bladder function are also sometimes compromised, with bloating, nausea, vomiting, and abdominal pain being a frequent complaint. Constipation is frequent and sometimes alternates with diarrhea, all of this producing a significant impact on quality of life, which conditions the development of comorbidities, with depression and social isolation, in addition to the economic and labor cost for the patient and the health system, by referring it to multiple medical specialties, which study it in a “fractionated” manner.

In this way, the disclosure of this pathology is important, to expand the diagnostic horizons in medicine and not only in the area of Otorhinolaryngology, since it is possible that some patients diagnosed with benign paroxysmal positional vertigo and many other diagnoses of vertiginous pathology and others really correspond to Dysautonomia. It is necessary to carry out complete physical examinations visualizing the human being in an integral way, as in the old medical school, and thus avoid the division of signs and symptoms that lead us to multiple diagnoses, which unfortunately the specialization and sub specialization of medicine has focused on medicine today.

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Changes in the Electrohippocampogram Under Conditions of Various Effects on the Reticular Formation of the Midbrain

Introduction

The study of the theta rhythm generation mechanisms revealed that its formation requires a connection between the hippocampus and the medial septal region. It is known that the neurons of this area are pacemakers of theta rhythm. Septal neurons have intense projections to all areas of the hippocampus [1,2]. In the absence of connections between the neural networks of the MSO and the hippocampus, the theta rhythm in the latter is not generated [3]. The pacemaker function of the medial septal region is regulated by projections from various stem structures: serotonergic projections of the raphe nuclei suppress the theta rhythm, and glutamatergic projections of the nuclei of the reticular formation and dopaminergic projections from the ventral tegmental region increase theta rhythm. All this proves that the theta rhythm depends on the preservation of connections between many brain structures [4,5]. Reticular formation of the brain stem has ascending influences on the cerebral cortex, as well as on the structures of the diencephalon and limbic system. The nonspecific structures of the midbrain and pons are the final destination of the impulses coming from the hippocampus through the system of the medial forebrain bundle and, at the same time, one of the two main sources of afferentation for the hippocampus. Taking into account the data available in the literature that the launch of the theta rhythm and an increase in its frequency in proportion to the flow of incoming information is carried out by the ascending activating reticular formation [6,7], the aim of this study was to study changes in the electrical activity of the CA1 and CA3 fields of the dorsal hippocampus, its ventral region, the dentate fascia, and the medial septal nucleus under conditions of electrical and chemostimulation of the reticular formation.

Methods

The research was carried out on Chinchilla rabbits (25 pieces) weighing 2.5-3 kg. EEG was recorded from the dorsal (fields CA1: P3; L2; H8 and CA3: P3; L6; H7.5) and ventral hippocampus (P4; L7; P17), dentate fascia (P4; L5; H7.5) and medial nucleus septum (A-3; L0.5; H10.5) before and after stimulation (electrical and chemical) of the reticular formation (P9; L2.5; H18.2) of the brain stem. The blockade of the reticular formation was performed with a 10% solution of novocaine. To control the rabbits in the study area was injected with saline in a volume equal to the injected solutions.

Results and Discussion

Unilateral electrical stimulation of the reticular formation at sufficiently low stimulation parameters (5-10 Hz; 50-100 μA; 0.5 ms) for 15-30 sec did not lead to visible changes in the electrical activity of the studied brain structures. Optimal for inducing electrophysical changes is stimulation with rectangular pulses with a duration of 0.5 ms, a frequency of 10-20 Hz, and a current of 100- 200 μA. From the first minutes after exposure to electric current, in the total activity of fields CA1 and CA3 of the dorsal hippocampus, its ventral region, dentate fascia and medial nucleus of the septum, an increase in the severity of the theta rhythm was observed against the background of a decrease in fluctuations in the beta range, an increase in the amplitude of activity of the ipsi- and contralateral side. Similar data were observed by us with the introduction of low doses of carbocholine - 0.5-2 μg into the reticular formation. Analysis of the frequency spectrum of the ipsi- and contralateral hippocampus revealed an increase in the rhythm of the oscillatory process, a shift of waves from the range of 3-5 vibration/s, which corresponded to the state of rest, to the frequency spectrum of 6-7.5 vibration/s. A decrease in the representation of fast-frequency beta oscillations is noted. Amplitude analysis showed a sharp increase in the amplitude of the waves of the studied brain structures (Figures 1A & 1C).

At 3-5 seconds, ordered activity transforms into convulsive discharges. Such hyperactivity appears synchronously in all the studied areas of the brain and is recorded for 3-4 hours after electrical stimulation of the reticular formation. Epileptiform activity in the hippocampus was also noted by us with an increase in the dose of carbocholine to 3 μg. A further increase in the parameters of the stimulating current (50-100 Hz, 200-300 μA) leads to the registration of a pronounced desynchronized activity, which combines both theta waves and fast-frequency beta oscillations. In the electrogram of the hippocampus, there is a violation of the rhythm of the oscillatory process and the dominance of highfrequency waves in the spectrogram. The performed frequency analysis revealed a violation of the order of oscillations, which was noted in the case of the use of high parameters of the irritating current, and an increase in the representation of fast frequencies. Amplitude analysis showed a slight decrease in the amplitude of the waves of the registered brain structures (Figure 1B).

Figure 1: Amplitude-frequency analysis of the electrical activity of the ipsilateral hippocampus before and after low-frequency (A), high-frequency (B) electrical stimulation and applications of carbocholine (C) in the reticular formation of the midbrain. I - frequency, II - amplitude analysis. On the abscissa axis - the average value of the classes of intervals in frequencies, on the ordinate axis - the frequency of repetition; The solid line is before, the dotted line is after exposure.

Application of 5-OT into the reticular formation at a dose of 10-30 mcg from the first minutes of administration causes the appearance of regular, synchronized activity of increased amplitude in various areas of the hippocampus, dentate fascia and medial nucleus of the septum. With an increase in the dose of the administered substance, the electrogram of the structures changes and passes from rhythmic, ordered activity to epileptiform. Restoration of the electrical activity of the studied brain structures to the background level was observed at 150-180 minutes. Spectral analysis of the EEG fields CA1 and CA3 of the dorsal hippocampus, its ventral region, dentate fascia, and medial septal nucleus revealed the dominance of waves in the range of 5-6 counts/s, a decrease in the representation of fast-frequency beta oscillations. Amplitude analysis showed an increase in the amplitude of the activity of the studied brain structures (Figure 2А). At 3-5 minutes of administration of 10-20 μg of norepinephrine into the reticular formation, in all areas of the hippocampus, dentate fascia and medial septum nucleus, synchronized, ordered, regular activity is recorded, the representation of high-frequency waves decreases and the amplitude of activity of the studied brain areas decreases somewhat. Restoration of the electrohippocampogram to the intact level is observed at 90-120 minutes.

The performed frequency analysis revealed a shift in the frequency spectrum and the dominance of waves in the range of 4-5 counts/s, a decrease in the representation of fast-frequency beta oscillations. Amplitude analysis showed a slight decrease in the amplitude of activity compared to the background indicator (Figure 2B). Temporary shutdown of the reticular formation by the introduction of a 10% novocaine solution causes significant changes in the EEG activity of the recorded brain structures: the theta rhythm disappears, although individual theta waves are present. The absence of rhythmic oscillations is preceded by the appearance of convulsive activity in the electrohippocamogram, after which irregular, low-amplitude activity is recorded, combining both slow waves and fast-frequency oscillations. The performed frequency analysis revealed a sharp decrease in the number of waves in the range from 5 to 10 counts/s and an increase in the number of delta and beta oscillations in both hemispheres of the studied brain structures. Amplitude analysis showed a significant decrease in the amplitude of the activity of the studied brain structures (Figure 2C).

Figure 2: Amplitude-frequency analysis of the electrical activity of the hippocampus (field CA3) before and after the application of 5-OT (A), NA (B), and novocaine (C) in the reticular formation of the midbrain. The rest of the designations are the same as in Figure 1.

Some scientists believe that the presence and frequency of the theta rhythm are determined by the frequency distribution of discharges in the cells of the septum (Gogolak, et al. [8]). When the reticular formation is stimulated by a current of increasing strength, the number of septum neurons that discharge in bursts increases, and the frequency of their bursts increases in parallel with the frequency of the theta rhythm. With a current strength that causes a change in the theta rhythm in the hippocampus by desynchronization, the number of rhythmically discharged cells decreases (they are inhibited or begin to give continuous high-frequency discharges without volleys), although a limited number of neurons continue to maintain high-frequency rhythmic discharges even under these conditions [8]. At a very high intensity of stimulation of the reticular formation, the high-frequency theta rhythm is replaced by desynchronization. According to some scholars, the shift theta rhythm frequencies are the result of a gradual change in the level of the input signal from the reticular formation to the septo-hippocampal system [9].

We have revealed the duality of electrical processes in the hippocampus during stimulation of the reticular formation. High-frequency stimulation of this area led to the registration of desynchronized, irregular, low-amplitude activity in various fields of the dorsal and ventral hippocampus, dentate gyrus, and medial septal nucleus. According to some scientists, these effects are determined by topographically and functionally different pathways and structures of the mesodiencephalic region [10]: the theta rhythm occurs when the dorsolateral region of the tegmentum and central gray matter are stimulated, and the transition of the theta rhythm to desynchronization with increasing current occurs when the ventromedial region is stimulated. reticular formation. The possibility of inducing desynchronization from the bulbar ventromedial tegmenta was also described by other researchers [11]. Many authors have shown that from the same point in the reticular formation it is possible to induce theta rhythm in the hippocampus at a low strength or frequency of stimulation and desynchronization with an increase in these parameters [12].

Considering all of the above, it can be assumed that, obviously, with an increase in the frequency and intensity of stimulation of the reticular formation, leading to the registration of desynchronized activity in the hippocampus, those sections of it that inhibit the secretion of corticosteroid hormones are activated. Different parts of the stem reticular formation take part in the implementation of neuroendocrine functions. A particularly important role is played by the reticular formation of the mesencephalic region, which has close anatomical and morphological connections with the hypothalamic-pituitary system [13]. It is known that cholinergic synapses are involved in the stimulation of the HPA axis [14], and a dose-dependent release of the hormone is noted [15]. In our experiments, the application of 0.5–2 μg of CH from the first minute led to the registration of well-defined, regular synchronized activity, which periodically alternated with epidischarges, which indicates an increase in the activity of hippocampal neurons. When hydrocortisone is applied directly to the reticular formation, the appearance of convulsive activity in the hippocampus is also noted.

In our experiments, the application of small doses of 5-OT (10–30 μg) to the RF of the midbrain led to the registration in various areas of the hippocampus, dentate fascia, and medial nucleus of the septum of regular, rhythmic, high-amplitude activity with dominance of waves in the range of 5– 6 counts / s, which, 2-5 minutes after the injection, combined short-term epidischarges recorded throughout the entire observation period (90-120 minutes). The data available in the literature testify to the activation of HPA when 5-OT is administered to various areas of the CNS [16]. Obviously, when the reticular formation is stimulated by 5-OT, the HPA system is activated, resulting in an increase in the concentration of ACTH and steroid hormones in the blood, which, by increasing the excitability of hippocampal neurons, lead to the registration of ordered, synchronized activity. Increasing the dose to 50-100 mcg leads to the registration of convulsive activity, which indicates an increase in the amount of steroid hormones in the blood, which lead to an increase in the excitability of hippocampal neurons. Similar data were obtained in electrophysiological studies [17].

Our data suggest a stimulating effect of NA on the HPA axis, leading to an increase in the secretion of ACTH and steroid hormones, which cause the theta rhythm in the hippocampus at low doses of NA and convulsive discharges with an increase in the dose of monoamine. Our assumption is confirmed by the data available in the literature on the stimulating effect of NA on the HPA axis. In addition, it has been shown that under the action of NA there is an increase in the secretion of corticoliberin, ACTH, and corticosterone [15]. Microinjection of HA into the surface plate in the region of the nuclei of the trigeminal nerve of the brainstem causes an increase in ACTH in the blood plasma [18]. Temporary shutdown of the reticular formation of the midbrain by the introduction of a 10% solution of novocaine leads to the registration of convulsive activity in the hippocampus, after which there is a decrease in the amplitude of the waves and the registration of irregular highfrequency oscillations. Similar data were obtained during bilateral coagulation of the reticular formation of the midbrain, where the disappearance of the theta rhythm and the dominance of fastfrequency oscillations in the EEG activity of the hippocampus were shown [17].

Given the presence of connections between the reticular formation and the hypothalamus and participation in the control of the hypothalamic-pituitary-adrenal system, it can be assumed that as a result of its temporary shutdown, a violation occurs in the regulation of the hypothalamic-pituitary-adrenal system, resulting in a decrease in the amount of steroid hormones in the blood, which leads to decreased excitability of hippocampal neurons. In favor of this assumption, some works can be cited that show a decrease in the secretion of hormones of the adrenal cortex after the destruction of the reticular formation [18]. Summarizing the material presented in this article, we can say that various effects on the activating reticular formation lead to its excitation, which is reflected in the appearance of theta rhythm in the hippocampus. The excitability of the hippocampus can also be judged by the appearance of convulsive discharges in its activity, indicating its pathological excitation. Temporary shutdown of the activating reticular formation in the first minutes also leads to epileptiform activity in the hippocampus, after which desynchronized, lowamplitude waves are recorded. The general properties of the reticular formation and its physiological significance in the body suggest its participation in the control of endocrine functions. Impulses emanating from the reticular formation, affecting the tone of various parts of the central nervous system, change their reactivity to the action of hormones circulating in the blood, thereby determining the intensity of influences from these parts of the brain on the hypothalamic-pituitary system. In addition, the impulses emanating from the reticular formation, reaching the endocrine effectors, determine the tone and reactivity of the latter to the action of humoral and nervous stimuli.

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