MALNUTRITION

 The concept of m. it has been further investigated and re-examined in the context of an extensive meaning that includes all the functional, anatomical-pathological, weight, and auxological biochemical alterations induced by quantitatively and qualitatively incongruous food intakes or by morbid conditions that hinder the normal use of nutritional factors.

According to a very widespread (albeit schematic and moreover not univocally understood) etiological classification, forms of m are distinguished. primitive (either by default: undernutrition or undernutrition; or by excess: hyper nutrition or supernutrition ), directly connected to the quantity and quality of food intake, and forms of m. secondary (which can also be by default or, more rarely, by excess), symptomatic of many morbid pictures (or in any case consequential to these).

The m. secondary can coexist with the primary one: for example, a subject already undernourished due to inadequate food intake can be affected by diseases that are in themselves the cause of malnutrition.

The existence of another possibility is sometimes taken into consideration, that of "m. due to imbalance", connected to a marked disharmony of distribution in the food ration, despite the fact that the overall energy intake (provided by carbohydrates, fats, proteins, possibly alcohol) is normal or even excessive. The unbalanced distribution of energy factors (e.g. adequate protein ration with excess fat and low carbohydrate intake) almost always implies a deficiency condition (absolute or more often relative, usually without apparent clinical manifestations), even when the conditions' general characteristics of the subject are apparently prosperous or even marked by obesity. In the latter case, there is, therefore, both an m. caloric excess, as much as an m. by default,

Understood in its broadest sense, the m. is responsible for multiple conditions of organic suffering, which can manifest themselves with overt symptoms (detectable with clinical, anthropometric, laboratory, and possibly radiological findings) or which, much more often, run asymptomatically for a long time ( occult or subclinical disease ), however, impairing the psychophysical efficiency or increasing the morbidity towards certain pathologies, especially degenerative ones.

Examined in its various aspects, the problem of m. primitive transcends its clinical (and moral) implications to also have an extreme economic interest, above all in consideration of the negative repercussions on working capacity, morbidity, and mortality, and therefore on the social costs of these phenomena.

Malnutrition by default

- With the exception of those simple foods which, within certain limits, can be interchanged with others (e.g., for energy purposes, fats can be replaced, within certain limits, with isocaloric quantities of carbohydrates), the deficient supply or the insufficient use of a nutritional factor involves a progressive depletion of its possible reserves in the tissues; therefore a cellular impoverishment, with compromise of some osmotic, enzymatic, and more generally metabolic processes; finally, the onset of cellular and tissue degenerative lesions, some reversible, others irreparable.

While in the initial or occult forms, the diagnosis is possible only through laboratory tests (dosing of the blood contents, and sometimes cellular ones, of vitamins, minerals, proteins, etc.; determination of the nitrogen balance, or other), in the overt forms the diagnosis from the simple collection of clinical and anthropometric data (weight ratio, plyometric values, etc.), even if it needs to be deepened by laboratory research.

Among the many causes in the world that contribute to the persistence of m. primitive by default, those of a socio-economic nature predominate (underdevelopment, hence poverty and subculture, therefore the poor flow of nutritional and health information) and of a geological and ecological nature (this is the case of the endemic goiter due to iodine deficiency, which affects many mountain populations of all the continents). Other significant causes are in relation to contingent or recurring events (such as famines and other natural disasters, long-lasting war events, and the like) or unfavorable cultural influences (restrictive precepts of a religious or philosophical nature; superstitions, prejudices, and food cravings; irrational diets; repeated fasts in protest) or to inadequacies in eating behavior, for various reasons (personal tastes, repulsions or unconscious refusals).

Forms of m. secondary by default are observed in multiple defending pathological conditions: in some endocrine diseases (such as Simmonds's disease and Basedow's disease), psychic, tumoral, metabolic, infectious, and toxic. The latter include iatrogenic avitaminosis from antibiotics (deficiency of vitamins B 2, PP, etc.). In such cases, dietary therapy (oral, tube, or parenteral) plays an adjuvant or non-prominent role, with the exception of various metabolic diseases (see metabolism, congenital diseases of, in this App.; replacement , diseases del, in this App.; dietetics, in this App.), for post-operative conditions (which mainly make use of parenteral nutrition), for dyspeptic syndromes and for intestinal malabsorption (sprue syndromes; enteropathies due to intolerance to gluten, mono- and disaccharides; malabsorption methionine, tryptophan, vitamin B12, folic acid; abetalipoproteinemia, etc.).

Malnutrition by excess. 

- The primitive form is widespread in countries with high economic development (see below) and among the privileged classes of depressed countries. It has many metabolic aspects, which will be mentioned later.

The secondary form can be pathological or iatrogenic in nature. In the first case, it usually takes the form of endocrine obesity (from hyperadrenalism, hypothyroidism, diencephalic lesions, etc.) in which, due to the compromised efficiency of some homeostatic mechanisms, a slowing down of the metabolism is determined, among other things. energy, a marked accentuation of anabolic processes, and, therefore, an abnormal hoarding of fat.

Physiological components

Physiological components

    While emotional behavior is largely regulated by relatively ancient and deeper brain structures, the frontal lobe of the cortex is involved in human anxiety. It is no coincidence that destructive surgery of parts of it reduces anxiety in patients suffering from these disorders. The most important 'building blocks' of the brain are the neurons or nerve cells. Connected in highly complex networks, they transmit information through chemical substances that act as messengers: neurotransmitters (v.). At least fifty types have been identified, which differ considerably depending on the location: some of them are linked to a particular anatomical structure, and others are scattered throughout the brain. When we talk about anxiety, the three most important neurotransmitters are norepinephrine (also called 'norepinephrine'), serotonin, and GABA. The latter is an inhibitory neurotransmitter that reduces the likelihood of activating nerve cells; unlike norepinephrine and serotonin, it is located throughout the brain. The strongest evidence of a GABA connection to anxiety comes from pharmacological studies, especially those of benzodiazepines, anti-anxiety drugs that enhance the effects of GABA by causing reduced anxiety, relaxation of muscles, and drowsiness; they also exert an anti-convulsant action. Norepinephrine is used by so-called adrenergic neurons; it forms in both the central and peripheral nervous systems. The strongest evidence of a GABA connection to anxiety comes from pharmacological studies, especially those of benzodiazepines, anti-anxiety drugs that enhance the effects of GABA by causing reduced anxiety, relaxation of muscles, and drowsiness; they also exert an anti-convulsant action. Norepinephrine is used by so-called adrenergic neurons; it forms in both the central and peripheral nervous systems. anti-convulsant action. Norepinephrine is used by so-called adrenergic neurons; it forms in both the central and peripheral nervous systems. anti-convulsant action. Norepinephrine is used by so-called adrenergic neurons; it forms in both the central and peripheral nervous systems.

    As for the norepinephrine of the brain, 70% of it is found in a small blue area (locus coeruleus) located in an ancient and deep part of the brain that has evolved over time. There are also relatively few adrenergic cells in the locus coeruleus, but each of them then spreads widely by making contact with at least 100,000 other neurons. Since noradrenergic pathways cover large areas of the brain, it is not surprising that norepinephrine is implicated in so many activities, such as sleep and wakefulness, attention, learning, arousal, mood, and anxiety. Electrical stimulation of the locus coeruleus produces fear-like reactions in animals, while pharmacological stimulation of the same area, e.g. through high doses of yohimbine, creates subjective anxiety in men. A little higher than the locus coeruleus are the raphe nuclei, where we find the neurotransmitter serotonin. Like norepinephrine, it spreads to many other areas of the brain and the spine.

    Low serotonin levels have long been thought to be associated with low mood and depression, but more recent pharmacological research indicates that how serotonin works may be important in understanding anxiety and its disorders. Drugs that increase the availability of serotonin not only improve mood but also reduce the incidence and intensity of panic attacks, are effective in the treatment of aggression, while, as a side effect, they cause a lowering of libido. This suggests that serotonin has something to do with the organization of instinctual behavior, whether it is expressed in the form of aggression directed towards others, or instead manifested in the form of aggression towards oneself, such as, for example, in the case of depression, sudden and intense anxiety, the urge to overeat and sexual urges. Serotonin and norepinephrine certainly interact, but the mechanisms of the interaction are not fully known. Physiological changes in states of anxiety are not limited to the brain. The brain and spinal cord, which make up the central nervous system, are connected to all other organs through the autonomic nervous system. This, in turn, is divided into the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system has adrenaline and norepinephrine as transmitters. Once the brain activates the sympathetic parts of the autonomic nervous system, (nor)adrenaline is released into the blood resulting in an increased heart rate, with the dilation of the pupils, the inhibition of the lacrimal glands, and the opening of the respiratory tract. All of these responses, mediated by (nor)adrenaline, constitute that 'emergency reaction' of a physiological type that we experience as fear. The parasympathetic nervous system opposes its sympathetic counterpart in various ways. If this system is activated, the neurotransmitter acetylcholine is released into the blood and a decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. While the sympathetic nervous system is activated in emergencies, when a reaction is needed, the parasympathetic system produces a relaxation response. inhibition of the lacrimal glands, the opening of the respiratory tract. All of these responses, mediated by (nor)adrenaline, constitute that 'emergency reaction' of a physiological type that we experience as fear. The parasympathetic nervous system opposes its sympathetic counterpart in various ways. If this system is activated, the neurotransmitter acetylcholine is released into the blood, and a decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. While the sympathetic nervous system is activated in emergencies, when a reaction is needed, the parasympathetic system produces a relaxation response. inhibition of the lacrimal glands, the opening of the respiratory tract. All of these responses, mediated by (nor)adrenaline, constitute that 'emergency reaction' of a physiological type that we experience as fear. The parasympathetic nervous system opposes its sympathetic counterpart in various ways. If this system is activated, the neurotransmitter acetylcholine is released into the blood and a decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. 

If this system is activated, the neurotransmitter acetylcholine is released into the blood, and a decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. While the sympathetic nervous system is activated in emergencies, when a reaction is needed, the parasympathetic system produces a relaxation response. The parasympathetic nervous system opposes its sympathetic counterpart in various ways. If this system is activated, the neurotransmitter acetylcholine is released into the blood and a decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. While the sympathetic nervous system is activated in emergencies, when a reaction is needed, the parasympathetic system produces a relaxation response. The parasympathetic nervous system opposes its sympathetic counterpart in various ways. If this system is activated, the neurotransmitter acetylcholine is released into the blood, and decrease in heart rate, narrowing of the pupils, secretion of the lacrimal glands, and constriction of the airways can be observed. While the sympathetic nervous system is activated in emergencies, when a reaction is needed, the parasympathetic system produces a relaxation response.

    The emergency reaction prepares the organism perfectly to respond to danger. As soon as the danger subsides, the parasympathetic nervous system takes over and mounts a relaxation response such as for example, a slowing heart rate and a lowering of blood pressure.

    The biological implant is highly adaptive in the sense that it allows us to react appropriately to danger, but the neural pathways implicated in anxiety often activate in the absence of real danger (false alarms) and this can be disabling for the individual. False alarms generally occur in the event that the emergency system is hypersensitive (e.g. the locus coeruleus can, through hyperactive and noradrenergic activity, expand even in the presence of very slight voltages), or in the case in which, through learning processes, subjects associate harmless stimuli with some catastrophe. Even if the origin of false alarms is psychological, this does not mean that the process excludes physiological factors. As we have seen, the association of events is done in cortical areas. The subject's memory may contain a misrepresentation of which events are dangerous (eg, spiders), but this is not a brain problem; conversely, if the individual is constantly anxious due to the relative unavailability of GABA, this in fact represents a real brain problem.

Effects of sleep injuries

The word 'experiment' will be used in a restricted sense, in order to make a clear conceptual distinction between the phenomenology of sleep and the work on the neurophysiological mechanisms of the sleep-wake cycle. ‟The name of the experimenter is given to someone who uses simple or complex investigation procedures to vary or modify, for any purpose, natural phenomena and make them appear in circumstances or conditions in which nature does not present them to him. In this sense, 'observation' is the examination of a natural phenomenon and 'experiment' is the examination of a phenomenon modified by the examiner" (see Bernard, 1865, p. 29). In this chapter, we will summarize the results of experiments in which coma, lethargy or insomnia, or any change in the sleep-wake cycle,

a) The ascending reticular formation

This line of research is closely related to the physiology of the ascending reticular system. We therefore refer to Bremer's article of the same name, whose main conclusions we will briefly summarize as an introduction to this part.

It was later seen that even the behavioral aspects of the awakening reaction can be reproduced with the stimulation of the reticular formation, in animals without narcosis and free in their movements (see Moruzzi, 1972, for the literature). These are phasic, short-lived effects.

The next step taken by Moruzzi and Magoun (v., 1949) was to suggest the hypothesis that the ascending reticular system was continuously, i.e. tonically, active and that its influence on the brain must be above a certain critical level to maintain vigil. The interruption of this ascending influence would be the cause of the coma that appears in the cat after the section of the midbrain, in the cerveau isolé preparation by Bremer (see is c). This syndrome would also be observed in humans after a lesion of the midbrain produced by trauma. Less complete disruptions of the midbrain, combined with hypothalamic lesions, would produce lethargy, thus explaining von Economo's observations. The demonstration that a continuous, 'tonic' activity was present in the reticular system was obtained following two different lines of research: a) reproduction of the syndrome of Corna del cerveau isolé with interruption of the ascending reticular projections (see Magoun, 19632; see Moruzzi, 1972, for literature); b) demonstration by microelectrode recording of the existence of a continuous, irregular discharge in reticular neurons.

A third step forward was made by C. Batini and others (see, 1959), when they demonstrated that a behavioral and electroencephalographic syndrome of insomnia, thus opposed to the coma syndrome of cerveau isolé, could be obtained by dissecting the brainstem a few millimeters backward, at the pontine level. This 'trigeminal mid pontine preparation' is characterized by desynchronized EEG and alert eye behavior. This observation and many others made following different research paths (see Moruzzi, 1963, 1972; see Bonvallet, 1966, for the literature) led to the conclusion that in the brainstem there is also a system that can be called ‛ deactivating', because it is antagonistic to the ascending reticular system which we have seen instead to be activating. These are populations of neurons with EEG synchronizing and hypnogenic effects.

In summary, at the end of the 1940s a unitary explanation of apparently unrelated observations, such as those of von Economo and Berger, appeared possible. This result was due to the demonstration of an ascending reticular system with an activating, tonic and phasic influence on the brain. Finally, at the end of the 1950s, the classic hypnogenic effects obtained with electrical stimulation (see Chapter 4) could be related in some way to the deactivating influences exerted by other structures of the brainstem.

b) The deactivating regions of the brainstem

All of these results were obtained in acute experiments and the chronic effects of brainstem sections were used only as a control. Chronic experimentation began to be used especially during the sixties. These experiments led to important results for the problem of the origin of the sleep-wake cycle. The demonstration that two opposing influences are exerted on the brain led to the hypothesis that the cycle itself, i.e. the alternation of sleep and wakefulness, could originate in the brainstem.

The history of chronic decerebration experiments is long (see Moruzzi, 1972, for the literature). However, we will only discuss the results obtained by J. Villablanca (v., 1966) on cats in which the brainstem had been separated from the brain with a section made at a higher level, i.e. just in front of the superior colliculi (decerebration collicular). These tall midbrain cats were followed for an extended period of time. It is, of course, impossible to define any state observed in brainless animals as sleep or wakefulness. All we can say is that, after chronic decerebration, it is possible to observe behaviors resembling those of the normal animal during sleep and wakefulness. After 15-20 days the cats were found crawling or sitting or even attempting to walk; the lids were open and the pupils dilated. These were manifestly symptoms of wakefulness and this impression was reinforced by the fact that these periods alternated with states characterized by bodily manifestations of sleep. Villablanca (ibid .) made a distinction between a state characterized by the closing of the eyelids, by the lifting of the nictitating membrane, and, above all, by the fluctuation of the pupil diameter (fluctuating miosis) - which corresponds to the synchronized sleep of the intact animal - and a state characterized by the narrowing extreme of the pupils (fissured myosis) and by the generalized collapse of the postural tone, which corresponds to the desynchronized sleep of the intact animal. The periods characterized by the reversible disappearance of decerebrate rigidity are usually called 'cataplexic episodes', from the name of a clinical syndrome that we will examine later.

The main result obtained by Villablanca with his experiments is not the demonstration that fragments of sleeping or waking behavior can be observed in the absence of the brain - this had already been seen by others before him - but rather the demonstration that it is both the sleep-wake cycle and the rhythmic alternation of the two stages of sleep can arise when the brainstem is separated from the brain. Of course, only the cranial nerves and spinal cord are available for sleep and waking manifestations when the brain is absent. But it is a fundamental achievement to have demonstrated that rhythms of this type can arise, in a brainless animal, in the brainstem.

The obvious explanation for these results, if we overlook the problem of paradoxical sleep, is that there is an alternation of activity between two systems: the ascending or activating reticular system and the deactivating regions of the caudal part of the brainstem. Recent research has allowed us to locate at least two of these deactivating regions: 1) the region of the solitary tract, which is endowed with phasic activities, as demonstrated by lesion and stimulation experiments (see Moruzzi, 1963; see Bonvallet, 1966, for literature); 2) the nuclei of the raphe, which are tonically active, as demonstrated by prolonged insomnia produced by their lesion (see Jouvet and Renault, 1966). These are two independent systems, and this is demonstrated by the fact that it is still possible to produce synchronization of PHEO and miosis by stimulation of vagoaortic afferent fibers leading to the region of the solitary bundle. This deactivating effect is also present when the raphe crossing has been interrupted by a sagittal section (see Puizillout and Ternaux, 1974).

c) Alternation of activities and reciprocal connections between antagonistic systems

Chronic experiments on the cerveau isolé show, on the other hand, that a sleep-wake cycle can also arise in an isolated brain, after a complete section of the midbrain. Bremer's classic experiments were clever and the main result was the discovery that the sleep-wake cycle was present after the section of the cervical cord at C 1 , i.e. when the brain was still connected to the brainstem ( encéphale isolé ), while the period disappeared, and was replaced by a 'permanent' coma after the section of the midbrain ( cerveau isolé). Manifestly either the abolition of the flow of sensitive and sensory impulses through the cranial nerves, as Bremer had originally suggested (see, 1937 and 1938), or the suppression of an ascending influence arising between the two sections could explain such differences evident between these two acute preparations. We now know that the elimination of the tonic influence of the ascending reticular system is responsible for the acute cerveau isolé coma.