ZESPÓŁ NIEWYDOLNOŚCI WIELONARZĄDOWEJ U NOWORODKÓW: ZNACZENIE FUNKCJI SPOŁECZNYCH I ANATOMICZNO-CZYNNOŚCIOWYCH (PRZEGLĄD LITERATURY)

Dmytro A. Skurupii, Evgeniy G. Sonnyk, Vitaliy M. Sizonenko

Higher State Educational Institution of Ukraine «Ukrainian Medical Stomatological Academy», Poltava, Ukraine

ABSTRACT

Protection of maternal health as well as protection of fetal and newborn health is a strategic objective in all countries. It ensures the formation of healthy generation as the basis of gene pool preservation and further development of the nation. It is known that the progress of critical conditions in newborns is different from classical concepts. Аnatomicofunctional features of the newborns (especially premature newborns), the effect of prenatal pathological factors are provocative and background factors of the multiorgan failure syndrome begining in these patients, which probably affects frequency of appearance of this syndrome, the mechanisms of development, clinical manifestations, the final of the disease and makes doctors to consider newborns in critical conditions as high-risk group for multiorgan failure syndrome appearance.

 

Wiad Lek 2018, 71, 3 cz. II, -780

 

Protection of maternal health as well as protection of fetal and newborn health is a strategic objective in all countries. It ensures the formation of healthy generation as the basis of gene pool preservation and further development of the nation. The level of child morbidity and mortality rates is a measure of level of development of the country. The practical reflection of this problem internationally enshrined in the United Nations Convention on the Rights of the Child [1]. In Ukraine this problem is more acute than in developed countries because natural population growth rate for a long time remainі negative. A key element of a possible resolution of this issue is to improve the provision of obstetric and neonatal medical care, because, despite the presence in Ukraine extensive system of medical institutions that provide such assistance, and relatively satisfactory staffing of medical personnel, the level of perinatal and newborn mortality rates exceeds that rates of the European Union [2]. The solution lies in the development of clinical perinatology and perinatal pharmacology, targeted scientific and practical research of new methods in intensive care and newborn intensive surveillance [3].

It is known that the progress of critical conditions in newborns is different from classical concepts by its atypical symptoms, rapid development, difficulties in pathogenetic correction of dysfunctional disorders due to less functional resistance of organs and systems in children, and a variety of their anatomico-functional features. This statement can be postulated and in relation to definition of multiorgan failure syndrome as a possible course of critical condition in newborns [4].

General trends of growth and development in the neonatal period are anatomo-functional features themselves. Neonatal period lasts from birth to 28 days and divided into early neonatal period (7 days) and late one (7 to 28 days). This period characterizes the processes of adaptation to extrauterine living conditions, which leads to tension in adaptive mechanisms of the body. The mechanism is phylogenetically conditioned and designed to counteract the birth stress. These physiological features cause unique approach to determine treatment tactics in newborns: it must be chosen so as not to interfere with the effective functioning of their own evolutionary developed mechanisms of sanogenesis. It should be noted that the neonatal period is the period of unstable functional balance. The failure of this functional balance can be caused by factors that can be ignored in older patients. Anatomicofunctional features in neonatal period, that affects the course of multiorgan failure syndrome, can be determined almost in all organs and systems, namely [5]:

I. Nervous System:

1) defense mechanism of the nervous system is a generalized diffuse reaction (hyperthermia, apnea, tachypnea, seizures, etc.) to any external stimuli due to unfinished interneuron communications and incomplete differentiation of nerve cells;

2) low speed of nerve impulses due to incomplete myelination of motor fibers;

3) overresponsive reflexes. that occur through subcortical regions of the brain, impulsive stereotypical reflexes and athetose-like motor and convulsive reactions due to reduced effect of the cerebral cortex on thalamo-pallidar system;

4) susceptibility to cerebral edema and the rapid depletion of nervous reactions due to increased hydrophilicity of brain tissue;

5) prevalence of autonomic sympathetic effects. In terms of critical conditions, it is more stable cardiovascular functions and fast respiratory decompensation;

6) carotid sinus chemoreceptors sometimes do not work, which could lead to the apnea on the hypoxia background;

7) increased permeability of blood-brain barrier in newborns and young children, including exo- and endotoxins.

II. Thermoregulation system:

1) susceptibility to hypothermia due to:

rapid heat transfer due to the relatively large surface of the body;

high thermal conductivity through the tissue due to poorly developed subcutaneous tissue;

inability to increase heat production by shivering due to weak developed muscle tissue;

development of peripheral vasoconstriction, tissue hypoxia and metabolic acidosis in response to hypothermia;

insufficiently developed sweating, limiting heat loss with evaporation;

2) the possibility of uncontrolled hyperthermia due to:

limited heat loss through evaporation of insufficiently developed perspiration;

limited convection heat loss through the skin due to hyperfunction of sympathetic system (infection process).

III. Respiratory system:

1) lower than in adults, absolute levels of alveolar ventilation due to the smaller number and size of the alveoli, which causes a rapid decrease of alveolar ventilation with increasing dead space;

2) higher than in adults oxygen demand, which requires relatively large amounts of ventilation. This in leads to low partial pressure of carbon dioxide;

3) lesser sensitivity of neonates respiratory center to decrease ot partial pressure of oxygen retards breathing options adaptation in case of hypoxia;

4) increasing of breathing value in newborn in proportion to the increase in the frequency of respiratory movements, depth of breathing and airway resistance. This leads to the rapid development of respiratory failure and inability to reduce the value by increasing the respiratory volume in newborns.

5) horizontal arrangement of ribs, relatively weak development of respiratory muscles and high position of the diaphragm contribute to the rapid development of respiratory failure.

IV. Hemodynamic system:

1) arterial grid developed better than the venous and large vessels – better than microcirculation vessels, which contributes to a certain centralization of circulation;

2) capillary net has numerous anastomoses, providing adequate gas exchange in tissues;

3) tendency to sympathicotonia causes tachycardia and vascular spasm in response to pathological external influences. Hemodynamic has higher circulation speed, relatively lower systolic volume, higher heart rate and higher speed of volumetric blood flow per unit of body weight. These characteristics determine the compensation of high-speed circulatory hemodynamic of low specific resistance of blood vessels and cause a false picture of clinical compensation mechanisms on the background of hemodynamic disturbances.

V. Digestion system:

1) massive blood flow to the liver in the background of immaturity of its enzyme systems, contributes to the rapid depletion of the detoxification function, development of liver failure with hepatosplanchnic hemodynamic disorders;

2) Liver (including spleen) is one of the main organs of the reticuloendothelial system involved in phagocytosis, neutralization of bacterial toxins and the development of immune bodies, causing their role in lowering the immune resistance of the organism and the dissemination of infection on the background of spleen hemodynamic disorders;

3) intestinal permeability increased by active pinocytosis enterocytes and causes a high probability of bacterial translocation and immunogenic load by macromolecular peptides of intestine.

VI. Urinary system:

1) filtration ability of the kidneys is lower than in adults, the function of sodium reabsorption relatively high, which leads to fluid retention in the body;

2) low activity of the kidneys to ammonia synthesis and low phosphate content in provisionally urine determine the susceptibility of newborns to metabolic acidosis.

VII. Endocrine system:

1) low thyroid hormone promotes fluid retention;

2) synthesis 17-disoxycorticosteroids dominates the synthesis of 17-oxycorticosteroids because the former ones have lesser catabolic effects;

3) mediates stress reactions in newborns is predominantly norepinephrine;

4) the amount of insulin β-cells of the pancreas, prevails over the number glucagonic α-cells that produce glucagon, which on the one hand, helps ensure adequate energy supply to the cells on the background of increased basal metabolic processes in children, on the other hand – quickly leads to hypoglycemia in pathological conditions.

VIII. Blood system:

1) blood viscosity and hematocrit index higher than in adults, which reduces the flow of blood;

2) physiologic leuco- and erythrocytosis;

3) about 70% of all elements are formed by granulocytes, causing physiological shift in leukocyte formula in the left due to mature forms. During the first 5-7 days of life neutrophil percentage decreases nearly in two times, and the percentage of lymphocytes increases in two times;

4) About 70% of hemoglobin presented by its fetal fraction, characterized by high resistance to alkaline environment and strong binding abilities with oxygen. This lead to the low oxygen return to the tissues, resulting in the rapid development of tissue hypoxia.

IX. Fluid and electrolyte exchange:

1) the total water content in the body of the newborn is greater than in other age groups, and accounts for almost 80% of body weight mainly through extracellular fluid (about 40% of body weight);

2) on the 3rd-5th day of life transient negative water balance is observed;

3) the total loss of water is about 1750 ml / m2 / day, which leads to high (4-5 times higher than in adults) rate of water exchange and higher relative demand for water.

X. Acid-base status:

1) low buffer capacity of arterial blood contributes to metabolic acidosis even under physiological delivery;

2) a lower partial pressure of arterial carbon dioxide, which is formed as a respiratory acidotic state compensation, due to the low sensitivity of chemoreceptors can function and after reaching compensation, leading to the development of respiratory alkalosis.

XI. Catabolism: the need for materials is higher, due to the high intensity of basal metabolism and expenditure on growth and physical development;

1) inadequate qualitative and quantitative composition of nutrients quickly leads to disruption of physical and mental development disorders, dysfunctional system homeostasis factors weakening the immune response, adaptive responses violations, suppression of functional activity.

2) the need for protein per 1 kg of body weight is higher than in adults, and equals 4.0 g / kg / day;

3) to the essential amino acids in newborns additionally includes histidine, cystine and cysteine;

4) due to the accumulation of nitrogen in relation to plastic processes active indicator balance of nitrogen in newborns in the first 3 days of life is negative;

5) in children the total serum protein and protein fractions are different from adults towards hypoproteinemia, which reduces oncotic pressure of blood plasma;

6) low blood glucose causes the rate of development and severity of hypoglycemic states, in particular – due to the depletion of carbohydrate stores.

Thus, one could argue that the background to multiorgan failure syndrome in newborns is the rapid development of cerebral, respiratory, renal, hepatic enteric disease, disorders of hemodynamics, acid-base homeostasis, energy deficiency and regulations constants and clinical course of functional disorders of organs and systems have age differences, which should be considered in diagnosing multiorgan failure syndrome.

Nature of forming the newborn immune system, particularly of monocyte-macrophage link also leads to the tendency of this age group to development of the multiorgan failure syndrome. Fetal monocytes and macrophages are capable of production of proinflammatory cytokines at the beginning of the first trimester of pregnancy: active tumor necrosis factor -α, interleukin(IL)-6, IL-8 approaching this period the level of adult person and almost not changed during the prenatal period. At the same time, the activity of pro-inflammatory cytokines (IL-4, 10, transforming growth factor-β, the level of proliferation of T-lymphocytes, natural killer cytotoxicity) is directly proportional to the gestational age of the child [6]. During the first seven days of life changing the image of immune protection. Continuing a marked decrease in the number of circulating neutrophils, increase the proportion of lymphocytes, monocytes, eosinophils, immunoregulatory index (CD4 / CD8). Such changes known by the term “first physiological leukocyte crossroads”, possibly related to microbial contamination of previously sterile loci in newborn. In neutrophils also ascertain their ability to reduce adhesion, aggregation, uncertainty expression of L-selectin and adhesion molecules, resulting in the migration of leukocytes to inflammation and their ability to phagocytosis reduced. The noted quantitative compliance of monocytes to an adult, but their ability to migrate in inflammatory foci low. In the neonatal period there is a significant increase in levels of proinflammatory cytokines associated with stimulation of the monocyte-macrophage immunity, but in terms of physiological signs of syndrome of systemic inflammatory response were not observed [7, 8].

An important feature of the multiorgan failure syndrome in newborns is the fact that at the birth a child has clinic of this syndrome or the mechanisms of its development has been started. Among the prenatal causes of multiorgan failure syndrome the main role given to newborn and fetal hypoxia that can occur as a manifestation of asphyxia due to violation of utero-placental blood flow, or as a manifestation of fetal pathology (perinatal infection, trauma, congenital malformations). Intrauterine hypoxia and intranatal asphyxia are the main factors for perinatal losses. Perinatal hypoxia leads to a series of violations at the time of birth. Thus, in neonates with asphyxia at birth there is higher plasma glucose level compared with healthy children that is maintain that level the first two days. At 5-6 days of life glucose level in blood plasma is reduced compared to this level in healthy children; The same trend is observed in the study of red blood cells glucose. There is cell energy deficiency, the calcium imbalance, loss of mutual regulated relations between metabolically active enzymes. As a result of hypoxic effect on the time of birth a child has disorders of systemic and organ blood flow [9-12].

Among newborns should be separately identified group of premature newborns because their anatomical and physiological characteristics are different from more mature ones. According to the decree of Ministry of Health of Ukraine №179 from 29.03.2006 “On approval of Instruction on criteria perinatal period and live birth and death birth. Procedure for registration of live births and death birth “preterm (premature) newborn is considered live born child born or removed in the gestation of about 22 to 37 full week of gestation (154-258 days from the first day of the last normal menstrual cycle). These children will have more severely systems disfunction due to organ immaturity. In addition, it should be noted that with the current position of miscarriage factors seen as immune dysfunction, uterine-placental complex. Thus, women with miscarriage have changes in oxidase activity of granulocyte activation of neutrophils chemotaxis, increased alkaline phosphatase, lysosomal-cationic protein, myeloperoxidase, which are activators of inflammation present phenomenon vasospasm and increased adhesion-aggregation activity of blood vessels in the uterus and placenta, antiprogesterone activated antibody formation. Thus, prematurely born child can be considered as the patient with initiated mechanisms of the multiorgan failure syndrome. In addition, small gestational age of the child is traditionally accompanied by the presence of respiratory distress syndrome of newborns varying degrees of severity, which is associated with the terms of the production of surfactant. The first wave of surfactant synthesis is activated within 25-26 weeks of gestation and is associated with methiliation of ethanol. This path is exhausted to 35 weeks of gestation and extremely ineffective at the background of hypoxia. Second, phosphatitilcholinesterase path is activated only within 35-36 weeks of gestation. These physiology features of prematurely born child always lead to the presence in these patients a degree of hypoxia due to ventilation disorders [13].

Thus, anatomicofunctional features of the newborns (especially premature newborns), the effect of prenatal pathological factors are provocative and background factors of the multiorgan failure syndrome begining in these patients, which probably affects frequency of appearance of this syndrome, the mechanisms of development, clinical manifestations, the final of the disease and makes doctors to consider newborns in critical conditions as high-risk group for multiorgan failure syndrome appearance.

REFERENCES

1. United Nations: Convention on the Rights of the Child 1989, http://www2.ohchr.org.

2. Pasiieshvili N. M. Analysis of perinatal morbidity and mortality in the conditions of the perinatal center and ways of its reduction. Scientific journal «ScienceRise» №1/3(18).

3. Van den Anker J., Allegaert K. Perinatal pharmacology. Semin Fetal Neonatal Med. 2013, 18(1), 1–2.

4. Levin B.W. International perspectives on treatment choice in neonatal intensive care units. Social Science & Medicine 1990, Vol.30(8), 901-912.

5. Shkurupii D. A., Hryshko Yu. M. Age peculiarities of childhood in the aspect of the course and physical diagnosis of urgent conditions at the stage of primary health care. Actual problems of modern medicine: Bulletin of the Ukrainian Medical Stomatological Academy 2015, 15, № 4 (52), 142–144.

6. Erić Ž., Konjević S. Proinflammatory cytokines in a newborn: a literature review. Signa VItae 2017, 14(SUPPL 4), 10-13.

7. Kholod, D., Shkurupii, D., Sonnik, E. Immune changes in newborn newborns with gastrointestinal failure requiring intensive care. Georgian medical news 2016, 7-8 (256-257), 62–66.

8. Iliodromiti Z.,  Anastasiadis A., Varras M., et al. Monocyte Function in the Fetus and the Preterm Neonate: Immaturity Combined with Functional Impairment. Mediators of Inflammation 2013, Vol. 2013, Article ID 753752, 5.

9. Aufieri R., Picone S., Paolillo P. Multiple organ failure in the Newborn. Journal of Pediatric and Neonatal Individualized Medicine 2014; 3(2): e030254.

10. Mohammed L.H., Khairy M.A., El-Hussieny N.A. et al. Multi-Organ Dysfunction in Neonates with Hypoxic-Ischemic Encephalopathy. Med.J.CairoUniv. 2010, Vol. 78, No. 1, 461-467.

11. Bestati N., Leteurtre S., Duhamel A., et al. Differences in organ dysfunctions between neonates and older children: a prospective, observational, multicenter study. Critical Care 2010, 14, R202.

12. J.M. Melville, Moss T.J.M. The immune consequences of preterm birth. Front Neurosci. 2013, 7, 79.

13. Chakraborty M., McGreal E.P., Kotecha S. Acute lung injury in preterm newborn newborns: mechanisms and management. Paediatr Respir Rev. 2010, 11(3), 162-70.

 

ADDRESS FOR CORRESPONDENCE

Dmytro Shkurupii

Higher State Educational Institution of Ukraine

«Ukrainian Medical Stomatological Academy»

Shevchenko 23 str., 36011, Poltava, Ukraine,

tel: +380(66)2369670

e-mail: d.a.shkurupiy@gmail.com

Received: 11.03.2018

Accepted: 04.05.2018