infantile intestinal gripes

Infantile intestinal gripes — the most frequent complaint from which parents of children of thoracal age address to the pediatrist. As this term understand certain behaviour of the child which is accompanied by the expressed anxiety and we cry.

As crying, is inherent to all children of the first months of a life for acknowledgement of presence of gripes more accurate qualitative and quantitative signs are required. Such signs have been accepted by the Roman criteria III in which infantile intestinal gripes began to be surveyed for the first time as variant FRZHKT at children of early age. According to the given definition, MKK are attacks of anxiety and the crying, 3 hours proceeding more per day and 3 and more days in a week throughout a week [92] repeat. Crying at MKK has 3 prominent features:

1. In typical cases it appears from 2-week age and is as much as possible expressed on 2nd month of a life of the child, gradually decreases and disappears by 3-4 months;

2. Crying tends to intensifying by the evening, crying attacks arise and come to an end suddenly, without the external provoking reasons. Long, the child it is difficult to abirritate attacks;

3. Crying is accompanied by other symptoms which specify in its probable reason - abdominal pains. The child presses handles to a body, compresses cams, rolls out legs, curves a back. The person reddens, accepts suffering expression (a pain grimace). Frequently anxiety and crying
Are accompanied by an inflation and a stomach strain, a passage of flatus, sometimes a regurgitation. The appreciable simplification comes right after defecations.

In spite of the fact that attacks repeat often and represent a disturbing picture for parents, the general condition of the child is not broken. During the period between attacks it is quiet, normally adds in weight and has good appetite. According to the Roman criteria III, diagnostic criteria MKK should include the following:

1. Anxiety and crying attacks arise and disappear without any reason.

2. Episodes proceed 3 and more hours per day, 3 days in a week on an extent at least 1 weeks repeat not less often.

3. There is no backlog in development.

Diagnosis MKK can be put any child is more younger 4-5 months, crying and which anxiety correspond to the above-stated criteria and there are no signs of lesion TSNS or development disturbances, and also has normal indicators of physical development and has no deviations from norm of objective data. Nevertheless, the syndrome of gripes is enough general and does not specify in a source of a pain or certain illness. MKK can be implication of organic diseases approximately in 10 % of cases, therefore demand dynamic observation of the doctor and an exception of some diseases: congenital anomalies GASTROINTESTINAL TRACT, anomalies of urinary system, an invagination, a debut of intestinal infections, an allergy to fiber of the cow milk. Unlike MKK, at organic diseases GASTROINTESTINAL TRACT the given attacks are characterised by a persistent current and presence of additional symptoms which help with correct treatment and promote a timely establishment of the diagnosis. Such symptoms of alarm are:

1. Disturbance of weight increases.

2. Disturbance of psychomotor development.

3. Dyspnea and cyanosis attacks.

4. Presence of dermal symptoms (an eruption, edemas, a persistent hyperemia).



6. A persistent diarrhoeia and disturbance of character of a chair.

7. Persistent constipations.

8. Cramps.

9. Slackness, refusal of meal.

10. A fever.

MKK are inherent also to healthy children in other relations at normal physical and psychomotor development. Despite the big duration of crying children with MKK, in comparison with children of control group, at them do not have changes of a warm rhythm, difference of a tonus vagusa and level of a hydrocortisone [84]. At healthy not full-term children MKK begin later, than at full-term, that corresponds to 6 weeks corrected with the account of premature birth of age [96]. Authentic differences in frequency MKK at first-borns and subsequent children in a family it is noted, however mothers of first-borns nevertheless address with this complaint to the doctor, owing to inexperience and excitement [163] is more often. Frequency MKK depending on feeding type essentially does not differ, but after introduction of a milk admixture the pattern and a daily rhythm crying, in particular, intensifying of attacks and earlier age "peak" MKK [134] can change in the morning. Favorable current MKK and disappearance of symptoms by 3-4 months is peculiar to the majority of children, however at a part of patients attacks proceed during longer time. Any background disease can strengthen and prolong attacks MKK. Owing to a generality of reasons FRZHKT which can be combined with each other, it also promotes more persistent semiology. On time of occurrence and a current it is possible to allocate 3 forms MKK:

1. Typical: gripes appear from 6 weeks, accrue by 2 months, and then decrease and disappear by 3-4 months.

2. Persistent: inherent to children with an accompanying pathology, sochetannymi variants FRZHKT and additional risk factors, when gripes persistirujut and after 3-4 months.

3. Late: gripes appear after 3-month's age. At this form inspection of the child for an exception of the organic nature of disease is necessary.

Mechanisms of development MKK by present time remain up to the end not found out. Presence of several factors in pathogenesis MKK is possible. One of them - the assumption of a role in occurrence MKK of fiber of the cow milk (BKM), based on observation over reduction of attacks MKK after exception BKM of a food [112]. Despite lacking authentic differences in frequency of occurrence MKK at children on the thoracal and artificial feeding, the given mechanism cannot be excluded completely as some components BKM are present and at female milk. The most significant allergens of the cow milk - v-laktoglobulin and casein are found out in thoracal milk (less than 33 ng/ml) [94]. Other potential allergen - bull serumal immunoglobulin G is found out in comparable quantities in thoracal and cow milk. Its concentration has appeared rather variabelnoj in milk of different women, but was authentically above at mothers which children suffer MKK [94]. The allergy to BKM can be caused immune and not immune mechanisms. The sensibilization can be promoted by disturbance of an intestinal barrier which is still insufficiently generated in the first months of a life, owing to immaturity of an intestinal microbiocenosis and insufficient secretion secretory IgA. At children with MKK a hyperpermeability of a mucosa of a small bowel (SOTK), but are absent signs of loss of fiber through an intestinal wall (normal level of an a1-antitrypsin in a feces) and other signs of the allergic inflammation [133], typical signs of a manifestation gastrointestinalnoj to an allergy (a diarrhoeia, an exudative enteropathy, regurgitations) mismatch semiology MKK, and specific immunologic markers, in particular, risings IgE, at MКК do not find out. Frequency of an allergy in families of children suffering MKK, does not exceed that in control group [152]. On the other hand, MKK can be one of allergy symptoms to BKM, but in this case the clinical picture is usually more diverse and includes, along with them, dispepsicheskie
Disorders, and also dermal implications. In case MKK as implications FRZHKT, the sensibilization to BKM if takes place, possibly, has secondary character and it is caused by a hyperpermeability of an intestinal barrier.

Other prospective alimentary reason MKK the intolerance of lactose as consequence of immaturity of an intestinal epithelium and transitional laktaznoj failures (LN) can be. Researches of some foreign authors have shown, that concentration of hydrogen in exhaled air at children of the first months of a life is raised, that testifies to incomplete mastering of lactose, thus at children with MKK as basal, and postprandialnyj hydrogen level authentically above, than in control group [129]. Improvement of mastering of lactose occurs by 3-4 months, at that age when MKK pass. After a daily incubation of a milk admixture with a preparation of a lactase at 13 children with MKK time shorting crying approximately a day [73] becomes perceptible at 1 o'clock. However to eliminate MKK for the account of an exception of lactose not always it is possible [81].

Motility disturbances GASTROINTESTINAL TRACT can cause MKK as consequence of retardation of transit of intestinal contents, in particular some gas. In a rectum the intestinal hyperperistalsis and pressure rising has been found out in children of the first months [125]. Motility disturbances are limited to an intestine, stimulated with a suction and do not differ depending on feeding type, thus they essentially vary at different children. According to ultrasonic and an electrogastrography [164], at children with MKK the various disturbances of a motility in most cases accompanied by retardation of evacuation of nutrition from a stomach take place. Time of intestinal transit at MKK does not differ from norm [109], influence attempt on this indicator by appointment of the admixture enriched by alimentary fibers (soya polysaccharides), has not crowned success.

Level research gastrointestinalnyh hormones in blood at children with MKK has shown, that irrespective of a kind of feeding at them concentration motilina is raised, and level of Gastrinum and vasoactive intestinalnogo a peptide does not differ from norm. Moreover, rising motilina from the moment of a birth becomes perceptible at those children who suffer subsequently MKK, it
Remains raised to 3 months [141]. Throughout the first months of a life serotonin level in blood high, and cholecystokinin - low [88]. The first is the major nejrotransmitterom and regulates a motility GASTROINTESTINAL TRACT, and the second - participates in perception of a pain and feeling of saturation and influences rate of evacuation of nutrition from a stomach and on an intestine motility. Level melatonina in blood at newborns is high enough, then quickly decreases in the first weeks of a life and again raises by 3 months [173]. Melatonin matters in formation of a pattern of a dream and wakefulness. Probably, age and individual fluctuations of level of these hormones matter in occurrence of syndrome MKK. Transfer of a pain and bound with notsitseptsiej kognitivnaja system functions to the full by the birth moment. As painful impulses are transferred mainly on nemielinizirovannym to the S-fibres, the finished myelination of spending ways is not obligatory for successful transfer of painful impulse in TSNS. Transfer notsitseptivnyh signals is carried out at a foetus from 24th week of pre-natal development, and nejrotransmittery are found out on 12-16th week gestatsii. Hence, entering, transfer and reactions to painful impulses are present even at a foetus, and antinotsitseptivnaja the system inhibiting a pain, is formed later.

Food intake represents the physiological mechanism of calm of the crying child. But abirritating action of nutrition probably only under condition of a maturity antinotsitseptivnoj systems. The research spent at children during crying, has shown, that the abirritating effect from sucrose drawing on tongue of crying babies with MKK has been lowered, in comparison with children without MKK [101]. It can explain absence of abirritating action of feeding during attack MKK and specifies in the possible central mechanisms supporting manifestation MKK. The Same mechanisms can lay and at the heart of hypersensitivity, that is the minimum stimulus lead to an overexcitement of perceiving central neurones. The intestine stretching, a peristalsis which in norm should not cause any sensations, cause a pain and discomfort. The similar concept of a visceral hyperalgesia and
allodinii it is similar well-known at some FRZHKT at adults. The given concept explains presence of the factors causing the same symptoms and why, despite elimination of one of factors, these symptoms remain. Before the inhibiting system will not come in balance with raising, the child keeps a hypersensibility on any stimulus which can become reason FRZHKT, same the favorable current of these disorders and possibility of their correction only at the expense of regimen and diet updating, without application of any medicines speaks.

If MKK were shown exclusively by attacks crying and anxieties, it would be possible to assume, what exactly the central regulating mechanisms are the cores in their development. But presence of such characteristic symptoms as an abdominal distention, flatulentsija, and also calm of the child after a passage of flatus and a chair, specify what the intestine, is a source of painful stimulus. The possible role transitional LN which can cause MKK at a part of children was above discussed. The raised formation of hydrogen in the course of bacteriemic fermentation of not split lactose becomes an anxiety source in this case, most likely. Gas stretches an intestine, causing a pain, and available imperfection of regulation of a motility promotes disturbance of its deducing outside. However in occurrence MKK it is possible to look at a gas role more widely, not being limited to problem LN explaining occurrence of symptoms only at a part of children with gripes. Intestinal gas in itself can cause MKK and accompanying symptoms: abdominal distentions, rumblings, flatulentsii. As the child eats repeatedly within day the maximum accumulation of gas in an intestine occurs by the evening that explains daily rhythm MKK. But the X-ray inspection has not taped correlation between expression MKK and quantity of gas in a cavity of an intestine [115].

The efficiency estimation simetikona (vetrogonnoe an agent) at MKK has not shown its authentic advantages before platsebo [26]. Possibly, MKK peristalsises and antiperistalses are caused by not so much quantity of gas, how many its structure and the broken passage, intensifying thus.
Intestinal gas grows out of a bacteriemic fermentation of the various substances arriving with nutrition, and can essentially differ on structure. At children on thoracal feeding it is presented mainly by hydrogen formed at fermentation of not soaked up carbohydrates (lactose, oligosaccharides, glycoproteids). In process of food expansion, in an intestine there can be a methane, a carbon dioxide and hydrogen sulphide. Methane is formed strict anaerobami at digestion of fiber and carbohydrates, hydrogen sulphide - at fiber digestion. The structure of intestinal gas depends both on character of a food, and from enzymatic activity GASTROINTESTINAL TRACT and qualitative structure of a microflora of an intestine. According to J. Scheiwiller from co-workers. [117], the child from first days is capable to digest oligosaccharides. As neither that, nor other substrate are not digested digestive enzymes, it reflects change of character of a microflora of an intestine. Methane production is possible on artificial feeding, it considerably raises after feeding up introduction. Approximately 40 % of healthy Europeans and almost 100 % of Africans excrete methane, and ability to its formation has family character, is registered on an empty stomach and does not depend on the substrate accepted during research, that is, it is defined only by individual structure intestinal mikrobioty. Production of hydrogen sulphide and the ammonia possessing potential cytotoxicity, is inherent to a proteolytic anaerobic microflora and can be caused both high entering of fiber with nutrition, and its incomplete mastering. For example, reception of difficultly acquired soya fiber by children in the first months of a life is accompanied by formation of hydrogen sulphide and more frequent development of gripes [159].

Thus, the gas structure in an intestine can promote occurrence MKK, and it, in turn, is defined by structure of an intestinal microflora. Metabolic action of an intestinal microflora is not limited to an aerogenesis. The major products of bacteriemic splitting of not digested carbohydrates are korotkotsepochechnye fat acids (KTSZHK), first of all acetic, propionic and oil. Their concentration in a colon
The adult person is made by 70-140 mmol/l in proximal departments of a colon and 20-70 mmol/l - in distal.

The acetate is the basic metabolite of the heteroenzymatic fermentation inherent bifidobakterijam, and it is found out in a chair of healthy children from first days of a life. At the age of 1 month its level makes about 70-80 mmol/l [29]. It carries out the important power problems, being soaked up in blood and getting in cells of various organs and tissues, providing from 5 to 15 % of the general kalorazha. Butirat it is produced strict anaerobami which appear in an intestine of the child later, therefore in the first months of a life its concentration in a feces is insignificant. However in further its level accrues, making at adults to all 1/3 KTSZHK a feces [117]. Butirat it is used as an energy source kolonotsitami and has direct influence on processes of neogenesis of an intestinal epithelium, strengthening its barrier functions. Butirat possesses antiinflammatory action, inhibiting the nuclear factor of inflammation NFkBи interfering deatsetilirovaniju histones [154]. The normal microflora of an intestine produces cores KTSZHK with a minimum quantity of their isoforms. At disturbance of a microbiocenosis and prevalence of proteolytic flora the quantity of fat acids with the big molecular weight and their isoforms increases, it can be a diagnostic marker disbioza an intestine [29]. Research of a spectrum of fat acids in a feces of children suffering MKK, has found out authentic differences in comparison with control group at the age of 3 months [128]. Differences concerned acids with longer chains, their isoforms prevailed. Thus bacteriological research of a feces has not taped essential differences of a microflora, except for more frequent seeding Cl. difficileв to group of children, suffering gripes. Differences of results of two different ways of an estimation of an intestinal biocenosis have once again confirmed the limited possibilities kulturalnogo a method. Disturbance of a spectrum of fat acids of the feces, found out in children with gripes, specifies in the important role disbioticheskih changes in development of syndrome MKK. As research had dynamic character, it has shown essential changes of a spectrum
Fat acids which occur during the period from 1 to 3 months [128]. Thus, MKK are observed during this period when occurs formation of an intestinal biocenosis and mikrobiota varies most dynamically.

Research, I. Adlerberth in 2009, has shown, that the qualitative structure of a microflora of the child depends on variety of factors: microfloras of an intestine and patrimonial ways of mother, a way of a delivery, applying term to a breast, character of feeding, application of antibacterial preparations and vaginal antiseptics in sorts, environments of the child, in particular - its stay in maternity home, hospital, resuscitation [75].

Modern molekuljarno-genetic methods allow to estimate all variety of an intestinal microflora which can reach 1000 kinds with larger reliability and differs strict individuality. Dynamic molekuljarno-genetic research of an intestinal microbiocenosis at children of the first year of a life confirms, that its individuality is traced already since a birth [99]. But in the first months of a life the microflora is rather small, astable, subject to external and internal influences. In the course of its formation are possible disbioticheskie deviations which can be reflected in a functional condition GASTROINTESTINAL TRACT and provoke formation FRZHKT.

By a number of researches it is shown, that at children with MKK the quantity laktobatsill is less, than at children without MKK [79]. Besides, other data show variety and total depression kommensalnyh bacteria at children with MKK in comparison with control group of children [76]. The intestinal microflora exists in constant interaction with an epithelium and immune system of an intestine, it posesses a role of a stimulator of immune system, both structurally, and is functional. Under the influence of microbic stimulus there is an activation of membranous and cellular receptors, the differentiation of Th-lymphocytes is regulated, there is a development of cytokines and secretory IgA, permeability of an epithelium decreases and the protective barrier of an intestine becomes stronger. Morfologicheski it is shown by a weak sign of an inflammation in a mucosa of an intestine (JUICE) - insignificant limfoplazmotsitarnoj
Infiltration of own plate. This weak inflammation reflects process of adaptation and can be recognised by "physiological".

One of inflammation markers in an intestine level kalprotektina in a feces can be. Kalprotektin is the inflammatory fiber reflecting degree granulotsitarnoj of infiltration of a mucosa, inherent to inflammatory process. Research kalprotektina in a feces at children of the first months of a life with MKK and without them, spent J.H. Roads from co-workers. (2009), has shown, that it is raised at all children, including at healthy at which it has averaged 19746 mkg/g, at norm at adults to 50 mkg/g), that indirectly confirms presence of weak degree of an inflammation JUICE at early age [76]. However at children with MKK level kalprotektina has appeared above, than in control group, more than in 2 times (41371 mkg/g, p=0,042). With the help molekuljarnoyogeneticheskogo a method it is revealed, that all children with MKK have disbioticheskie changes, in particular, more frequent presence Klebsiella, and also higher basal level of hydrogen at exhaled air. On the basis of the received data the conclusion has been drawn on great value of alteration intestinal mikrobioty and the inflammation bound to it JUICE in genesis MKK. Thus, in difficult process of formation of an individual intestinal microflora the failures fraught with failure of adaptation and a lesion JUICE with development not physiological, but a pathological inflammation are possible. Inflammation and motility communication is carried out, first of all, at level of interaction of immune and nervous systems of an intestine, and this communication two-forked. Lymphocytes of own plate possess a number nejropeptidnyh receptors (SP, CGRP, the VIP, SOM, etc.). When immune cells in the course of an inflammation liberate active molecules and mediators (prostanoidy, cytokines) enteral neurones express receptors for these immune mediators (cytokines, Histaminum, PARS, etc.) . By means of immunohistochemical and immunofljuorestsentnyh methods it has been shown, that Toll-like receptors (TLR) 3 and 7, distinguishing virus RNK, and also TLR-4, distinguishing lipopolisaharidy (components of membranes gramme-negative of bacteria), are presented not only in podslizistom and an intermuscular plexus
GASTROINTESTINAL TRACT, but also in sensory neurones of a back horn of a spinal cord [165]. Thus, enteral neurones can answer as inflammatory stimulus, and immediately to be activated bacteriemic and virus components, participating in process of interaction of an organism with its microflora. With the aforesaid account, it is possible to present pathogenesis MKK in the form of "vicious circle", a role of the starting factor in which, probably, the broken intestinal microflora plays. The microflora is a source of accumulation of pathological metabolites and the gases, having stimulating an effect on sensitive receptors of an intestine, causes failure of adaptation and inflammation development in JUICE as is immediate, and through inflammation mediators, influences enteral sensory neurones that the intestine motility leads to disturbance. In the course of an inflammation permeability JUICE that promotes a sensibilization amplifies, the inflammation is reflected in functionality of an intestinal epithelium, being accompanied by disturbance of digestion which aggravates semiology. Owing to age features of perception of a pain and prevalence notsitseptivnoj systems the dominant centre of a boring which is fixed in the form of a hyperalgesia and allodinii is formed.

At 5-10 % of children MKK remain after 3-6 months of a life and can have the remote consequences - reduction by duration of a dream (13,7 hours, against 14,7 hours per control group), frequent awakenings [120]. Among children with it is long existing (after 3 months of a life) MKK, dream disturbances remain and on the second year of a life. According to M. Wake (2006), at the age of 2 years at 12.4 % of children who had earlier MKK, noted disturbance of a dream [172]. These problems strengthened a depression of mother or stress at both parents. At children who have transferred MKK at early age, by 3 years dream disturbances in 3 times more often, in comparison with children who did not have MKK [119] become perceptible. Dream disturbances have been presented by difficulty of a backfilling and frequent night awakenings. Besides, at three-year children more often (on 60 % more often) irritability attacks were observed. According to R. von Kries (2006), at children who have transferred infantile gripes, at the age of 2-3 years negative variants were observed
Behaviour, besides, by 4 years dream disturbances (in 6 times more often against control group) and alimentary behaviour [171] remained. At children with MKK dream disturbances (difficulties of a backfilling, awakening more than 5 times for a night) were observed in 56 % of cases against 12 % in control group. Meanwhile the dream for children of thoracal, early age has huge value. In the course of a dream there is a development kognitivnyh functions - storing processes (spatial and procedural memory) and training processes. The separate periods of a dream (REM - rapid eye movement, fast movement of eyes) are important for mental development of the child:

• REM the period induces brain development during those moments when stimulus and environment impulses do not reach.

• Disturbances REM of a dream at early age has long-term adverse consequences.

• In REM the period oxygen consumption same high, as well as at wakefulness.

• Non-REM the dream is important for development of immune functions, and also endocrine system of an organism.

According to S Canivet (2000), children at the age of 4 years which have transferred MKK, authentically had dream and feeding problems is more often. At them more frequent negative emotions on a temperament scale, psychosomatic problems became perceptible. For this category of children the bad mood during meal, more frequent hospitalisation with complaints to abdominal pains is characteristic. Abdominal pains were classified in 35 % of cases as functional, in 65 % as a syndrome of an angry intestine [90]. Studying of psychomotor development of children at the age of 5 years which had disturbances of a dream, shows authentic depression of the general and verbal factor of intellectual development [131]. According to D. Wolke (2002), at children who had gripes in infancy, at the age of 8-10 years authentically meet boundary hyperactivity and disturbances of behaviour [176] is more often. It is necessary to notice, that disturbances of a dream at children are projected at adult age by the raised uneasiness, aggression, attention and concentration disturbance.


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Scientific source KUBALOVA Saida Sultanovna. CLINICAL VALUE LAKTAZNOJ of INSUFFICIENCY And MICROBIC DISTURBANCES AT FUNCTIONAL DISORDERS of the GASTROENTERIC TRACT At CHILDREN of EARLY AGE. The dissertation on competition of a scientific degree of the candidate of medical sciences. St.-Petersburg - 2014. 2014

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