Pathogenetic Justification of the Principles of Rehabilitation of Children with Urinary Tract Infection

The dissertation is devoted to the pathogenic justification of the principles of rehabilitation of children with urinary tract infection. The research is dedicated to the study of patterns of change in the structural-functional state of the urinary system in children in ontogeny, as well as the identification of mechanisms of formation of hyperreflexive and hyporeflexive types of bladder dysfunction. A conceptual scheme of the inclusion of pathogenic mechanisms of pathological types of dysfunction has been developed in the work, and the role of pelvic congestion as a single key link in the pathogenesis of both types has been proven. The key direction of the research is the assessment of the clinical efficacy of the method of variable zonal barometric exposure as a pathogenetically justified rehabilitation method directed at the elimination of congestion of the pelvic organs and the restoration of urodynamics of the lower and upper urinary tract departments in children with pathological types of bladder dysfunction.

Relevance of the Problem

Infectious-inflammatory diseases of the urinary system organs in children remain one of the actual problems of pediatric nephrology, which is due to the high prevalence of this pathology in pediatric populations, the tendency of the pathological process toward a latent, chronic, progressive course associated with dysregulation of immunological and non-immunological mechanisms (Tsaregorets A.D., Ignatova M.S., 2001; Tebleeva L.T., 2004; Falagas M.E., 1995).

Epidemiological studies indicate an annual increase in the number of nephrological patients in the pediatric population (Ignatova M.S., 1989; Korovina N.A., 1998; Papyan A.V., 2001; Zakharova I.N., 2001; Kazanskaya I.V., 2005). With an average prevalence of nephrological pathology in children of 29:1000, the frequency of urinary tract infection, including pyelonephritis, amounts to 18:1000 (Ignatova M.S., 2001).

According to the Chief Administration of Healthcare of the Irkutsk Oblast Administration, the increase in diseases of the urinary excretion system from 1999 to 2002 amounted to 5.7%, among adolescents this indicator was 9.2% (Boyko T.V., 2002), and the increase for 2000-2005 was 25.2%. Regional studies indicate an increase in this indicator by 2.5 times in the more contaminated Right-Bank District compared to the relatively clean Left-Bank District of the city, so the prevalence of urinary tract infections in the city of Irkutsk amounts to 58:1000 (Filipov E.S., 2002). Among the conditions under dispensary registration, diseases of the urogenital system occupy the second rank.

In recent years, the very concept of urinary tract infection in children has undergone a number of cardinal changes. This has concerned questions of etiology, pathogenesis, diagnostic methods, treatment, and prevention (Papyan A.V., 2001; Tebleeva L.T., 2003; Rubin R.H., 1991). The role of bacterial virulence factors of urinary tract infection has become known, genetic codes have been determined, such as the ability of an isolated bacterial strain to adhere to the uroepithelium, and so on (Ignatova M.S., 2001; Vyalkova A.A., 2001; Carroll K.S., 1994; Sobel J.D., 1997; Jakobson V., 1999).

Discussing the aggressiveness of microbial virulence factors and the possibility of urinary tract infection in each individual child, it is necessary to also consider the complex of protective factors of the macroorganism, which include mechanical, hydrodynamic, anti-adhesive, receptor-dependent, and immunological factors (Papyan A.V., 1997).

The modern concept of urinary tract infection is impossible without assessing the nature and determining the level of urodynamic impairment against the background of organic or functional ureteral obstruction (Lopatkin N.A., 1998; Loren O.B., 2001; Morozov A.V., 2001).

According to treatment protocols, antibacterial therapy in the acute period and supporting therapy with uroseptics during periods of subsidence of disease activity and clinical-laboratory remission, prescribed taking into account the clinical assessment of the degree of bacteriuria, do not always lead to the results that nephrologists expect (Vyalkova A.A., 1997; Zorkin S.N., 1999; Papyan A.V., 2001; Bergeron M.G., 1995; Chlevalier R.L., 1998; Hobermann A., 1999; Yong Choi, 2001; Goldraich N.P., 2002). It should be noted that the elimination of bacteriuria with sanitation of the urine does not always lead to the normalization of urodynamics and, consequently, the restoration of impaired functions of the urinary system departments (Morozov A.V., 2001; Kirillov V.I., Tebleeva L.T., 2004). A significant proportion of patients exhibit further disease progression with involvement of the upper urinary system departments - renal interstitial tissue (Papyan A.V., 2001; Kosilov K.V., 2003; Kirillov V.I., 2004; Rubin R.N., 1996; Garin E.N., 1998; Yong Choi, 2001; Rushton H.G., 1999; Jobal U., 1999; Levtchenko E. et al., 2001).

Thus, the most effective factors of antibacterial protection of the macroorganism cannot fully ensure a positive effect from the conducted treatment, which dictates the necessity of revealing non-infectious pathogenic mechanisms of urodynamic impairment and, consequently, justifying the need for targeted impact on them during patient rehabilitation.

The above indicates that at present the question of the relationship between the structural-functional state of the lower and upper urinary system departments in ontogeny, both in healthy children and in patients with urinary tract infection, has not been fully studied. The causes of persisting dysfunction of the lower urinary system departments after elimination of the microbial-inflammatory process activity have not been established. The role of urodynamic impairment from the lower urinary tract departments in the development and maintenance of the inflammatory process has not been definitively determined. A system of rehabilitative measures for patients with urinary tract infection during the clinical-laboratory remission period has not been developed, nor has it been pathogenetically justified.

In general, this determined the goal of the work, consisting in revealing the patterns and mechanisms of impairment of the structural-functional state of the urinary system in children after transferred urinary tract infections and developing, on this basis, a system of measures aimed at rehabilitating patients in various age periods.

To achieve this goal, the following main tasks were sequentially solved:

1. To reveal patterns of changes in the structural-functional state of the urinary tract in healthy children in ontogeny.

2. To reveal patterns of changes in the structural-functional state of the urinary tract in children with various types of bladder dysfunction.

3. To determine the relationship between urodynamic impairments of the upper and lower urinary tract departments in children with hyperreflexive and hyporeflexive types of bladder dysfunction.

4. To develop a conceptual scheme of the inclusion of pathogenic mechanisms of formation of pathological types of bladder dysfunction and to determine their role in the development of inflammatory diseases of the urinary system.

5. To pathogenetically justify and assess the clinical efficacy of the method of variable zonal barometric exposure in the rehabilitation of patients with various types of bladder dysfunction.

Scientific Novelty

For the first time, it has been established that the indicator determining the stages of formation of the urinary system and allowing the objective distribution of practically healthy children into age groups of 6-7 years, 8-11 years, and 12-15 years is the average effective bladder volume, which characterizes not only the state of the threshold of reflex excitability of the bladder but also, according to data of multifactor regression analysis, reflects the formation of interactions between bladder and kidney function.

Significant correlation coefficients between urinary system indicators at the age of 6-7 years reflect a multicomponent interrelationship between the function of the lower and upper urinary tract departments, both in boys and girls, which characterizes the formation of a mature type of micturition in this age period. A decrease in the number and density of these connections at ages 8-11 and 12-15 indicates the stability of the functional state of the urinary system at these stages of ontogeny.

The developed regional matrix of distribution of canonical values in age groups allows for the assessment of biological maturity of the urinary system in children.

New are the data on the difference in the structural-functional state of the urinary system in children with hyperreflexive and hyporeflexive types of bladder dysfunction, consisting in the fact that the formation of the hyperreflexive type of bladder dysfunction in patients is determined by changes in indicators characterizing the impairment of the contractile function of the detrusor, caused by a hyperergic state of the neuroreceptor apparatus, while the formation of the hyporeflexive type of bladder dysfunction is determined by changes in indicators characterizing the impairment of the storage function of the detrusor, caused by dysfunction of the vascular-muscular structures due to morpho-functional immaturity.

Discriminant analysis established that the final formation by the age of 12-15 years of the hyperreflexive and hyporeflexive types of bladder dysfunction is determined by different mechanisms of formation of the morpho-functional state of the urinary system: in boys - the middle volumetric flow rate of urine, bladder volume at the first urge, the number of micturitions, and the effective renal plasma flow of the left kidney; in girls - the storage and contractile function of the bladder and renal hemodynamics.

Conceptual schemes of the inclusion of pathogenic mechanisms of formation of pathological types of bladder dysfunction have been developed, and their role in the development of microbial-inflammatory diseases of the urinary system in children has been demonstrated. It has been shown that the single key link in the pathogenesis of hyperreflexive and hyporeflexive types of bladder dysfunction is pelvic congestion, with hypoxia and hypoxemia of the detrusor, leading to a change in energy metabolism and impairment of its functions.

Priority are the data on the use of the method of variable zonal barometric exposure in children with hyperreflexive and hyporeflexive types of bladder dysfunction, as a pathogenetically justified method directed at the elimination of pelvic organ congestion.

A conceptual scheme of the sanogenic mechanisms of variable zonal barometric exposure has been developed, the points of application of which are the pelvic venous plexus, the functional syncytium of smooth muscle cells, and the neuroreceptor apparatus.

The results of the comparative analysis of the clinical efficacy of the method of variable zonal barometric exposure and traditional treatment methods according to the CONSORT program have proven its high therapeutic and sustained effect.

A Russian Federation Patent No. 2166800, 2001, "Method of Modeling Acute Inflammatory Diseases of the Urogenital Organs," has been obtained on the topic of the work.

The theoretical and practical significance of the work consists in the fact that, on the basis of elucidating the patterns of formation of the urinary system in healthy children in ontogeny and revealing the mechanisms of formation of hyperreflexive and hyporeflexive types of bladder dysfunction, the application of variable zonal barometric exposure is pathogenetically justified, which allows children with pathological types of bladder dysfunction, against the background of improved microcirculation of the pelvis, to restore urodynamics of the lower and upper urinary tract departments.

The high clinical efficacy and sustained therapeutic effect of the method of variable zonal barometric exposure, proven by means of the CONSORT program, open new prospects in the rehabilitation of patients with pathology of the pelvic organs.

Main Propositions for Defense

1. The formation of physiological functions of the urinary tract in ontogeny in healthy children, according to multifactor discriminant analysis, is determined by changes in indicators characterizing the function of the lower urinary tract - the average effective bladder volume, the maximum volume, the middle volumetric flow rate of urine, and in girls an additional indicator is the number of micturitions. The developed matrix of distribution of canonical values in age groups allows for the assessment of biological maturity of the urinary system in children.

2. In boys at all stages of ontogeny, the formation of the hyperreflexive type of bladder dysfunction is determined by changes in the maximum bladder volume and renal hemodynamics, and in the age groups of 6-7 and 12-15 years an additional factor is the change in bladder volume at the first urge, indicating a hyperergic state of the receptor apparatus. In girls, the formation of the hyperreflexive type of bladder dysfunction is determined by changes in the middle volumetric flow rate of urine, residual urine volume, and impairments of the storage function of the kidneys.

3. In boys, the formation of the hyporeflexive type of bladder dysfunction in ontogeny is determined by changes in the maximum bladder volume, bladder volume at the first urge, and in the middle age group a qualitatively new indicator is the change in the middle volumetric flow rate of urine. In girls at the ages of 6-7 and 8-11 years, the formation of the hyporeflexive type of bladder dysfunction is determined by changes in the middle volumetric flow rate of urine, bladder volume at the first urge, and renal hemodynamics, while at the age of 12-15 years changes in the maximum bladder volume and residual urine volume are observed, which is due to dysfunction of the vascular-muscular structures as a result of morpho-functional immaturity.

4. The method of variable zonal barometric exposure is a pathogenetically justified and clinically effective method of rehabilitation of children with pathological types of bladder dysfunction, directed at the elimination of congestion, the restoration of urodynamics of the lower and upper urinary tract.

Validation of the Work

The materials presented in the dissertation were reported and discussed at medical conferences of the MUZ GIMDKB (1997-2004); sessions of the Irkutsk Regional Association of Pediatricians (1997, 1999, 2001); the P-th Regional Scientific-Practical Conference "Actual Questions of Pediatric Uronephrology" (Vladivostok, 1998); the conference "Modern Aspects of Urolithiasis" (Novosibirsk, 1998); the I Conference "Ecology and Health" (Irkutsk, 1999); the II Congress of Pediatric Nephrologists of Russia "Modern Technologies in Nephrology and Pediatric Urology" (Moscow, 2000); the scientific conference "Actual Questions of Pediatrics of the Irkutsk Oblast" dedicated to the 20th anniversary of the creation of the pediatric faculty of IGMU (2001); the Russian Scientific-Practical Conference "Actual Problems of Nephrology: Urinary Tract Infection in Children" (Orenburg, 2001); the international school on pediatric nephrology "Actual Problems of Pediatric Nephrology" (Vladivostok, 2001); the IX Congress of Pediatricians of Russia. Russian Healthcare: Development Strategy (Moscow, 2001); the I All-Russian Congress "Modern Technologies in Pediatrics and Pediatric Surgery" (Moscow, 2002); the IV International Conference Irkutsk-Grenoble-Ulan-Bator "Actual Questions of Perinatal Pathology" (2003); the All-Russian Congress "Man and Health" (2004); at the session of the expert commission of the Dissertation Council D.001.054.01 at the State Unitary Enterprise VSNTS SO RAMN (2005).

Volume and Structure of the Dissertation

The work is presented across 270 pages. It consists of an introduction, a literature review, an exposition of materials and methods, 4 chapters of original observations, a conclusion and summaries, a list of references, and an appendix. The work is illustrated with 33 figures and 82 tables. The list of literature sources includes 253 works, of which 176 are in Russian and 77 in foreign languages.