Causes and pathogenesis of vesicoureteral reflux

Vesicoureteral reflux has a variety of causes.

The main cause of primary vesicoureteral reflux is a congenital malformation of the ureteral orifice:

• persistent gaping of the orifice (“funnel-shaped” configuration of the ureteral orifice);
• location of the ureteral orifice outside the Lieto triangle (dystopia of the ureteral orifice);
• short submucous tunnel of the intravesical part of the ureter;
• duplication of the ureter;
• paraureteral diverticulum.

The main causes of secondary vesicoureteral reflux are:

• organic IVO (valve or stricture of the urethra, sclerosis of the neck of the bladder, stenosis of the external opening of the urethra);
• bladder dysfunction (BD, detrusor-sphincter incoordination);
• inflammation in the area of the Lieto triangle and the orifice of the ureter (with cystitis);
• shrinkage of the bladder ("microcystis");
• iatrogenic damage to the Lieto triangle area and the ureteral orifice (operations with dissection of the smooth muscles of the detrusor or impact on the ureteral orifice: ureterocystoanastomosis, bougienage of the ureteral orifice, dissection of the ureterocele, etc.).

It is impossible to understand the causes of vesicoureteral reflux without understanding the normal structure of the vesicoureteral junction. Anatomically, the closing function of the vesicoureteral junction is achieved due to the ratio of the length and width of the intravesical section of the ureter (5:1), the oblique passage of the ureter through the wall of the bladder. The long submucosal tunnel is a passive element of the "ureterovesical valve". The active element of the valve mechanism is represented by the muscular-ligamentous apparatus of the ureter and Lieto's triangle, which closes the orifice when the detrusor contracts.

The causes of non-physiological urine flow include pathological conditions that lead to a disruption of the closure mechanism of the vesicoureteral junction and high intravesical fluid pressure (urine). The former include congenital defects of the vesicoureteral junction and an inflammatory process in the area of the superficial or deep triangle of the bladder ( cystitis ). Disrupting the function of the detrusor or the vesicoureteral junction itself.

Anomalies of the vesicoureteral junction often result from abnormal development of the ureteral outgrowth of the Wolffian duct during the 5th week of embryogenesis. Types of anomalies of the vesicoureteral junction:

• wide, constantly gaping form of the ureteral orifice:
• location of the ureteral orifice outside the bladder triangle (lateral position):
• complete absence or shortening of the submucosal tunnel of the vesicoureteral junction:
• disruption of the normal morphological structure of the vesicoureteral junction (dysplasia).

Loss of the vesicoureteral junction closure function occurs with inflammation of the bladder wall or the vesicoureteral junction area. Most often, secondary vesicoureteral reflux is a consequence (complication) of bullous (granular) or fibrinous cystitis. Infection of the urinary system occurs in 1-2% of boys and 5% of girls. Most often, the urinary tract is colonized by opportunistic (intestinal) flora, among which the main place is occupied by Escherichia coli (40-70%).

According to E. Tanagho (2000). the mechanism of development of secondary vesicoureteral reflux in acute cystitis consists of the following pathogenetic links: edema of the bladder triangle and the intramural part of the ureter disrupts the valve function of the vesicoureteral junction. Excessive increase in intravesical pressure during urination also contributes to reflux and increases the risk of pyelonephritis.

N.A. Lopatkin, A.G. Pugachev (1990) based on their own observations consider the occurrence of secondary vesicoureteral reflux in chronic cystitis as a result of the gradual spread of the inflammatory process to the deep layers of the bladder with "a breakdown of the antireflux apparatus of the vesicoureteral junction" and subsequent sclerotic and atrophic changes in the intramural section of the ureter. On the other hand, long-term chronic inflammation in the neck of the bladder often leads to stenosis of the urethra and impaired urodynamics, which also leads to the occurrence of secondary vesicoureteral reflux.

Normally, the vesicoureteral junction is able to withstand intravesical fluid pressure of 60-80 cm H2O. High hydrostatic pressure is a consequence of IVO or functional disorders of the bladder. IVO develops with valves of the posterior part of the urethra in boys, congenital sclerosis of the cervix of the bladder (Marion's disease), stenosis of the external opening of the urethra in girls, cicatricial phimosis.

Neurogenic bladder dysfunctions occur in 20% of children aged 4-7 years. By the age of 14, the number of people suffering from neurogenic bladder dysfunction decreases to 2%. Neurogenic bladder dysfunctions manifest themselves as irritative or obstructive symptoms. The main forms of neurogenic bladder dysfunction are: bladder overactivity, detrusor hypotonia, and detrusor sphincter dyssynergia. In these conditions, vesicoureteral reflux is also considered secondary and is a consequence of increased fluid pressure in the bladder. Bladder overactivity is characterized by sharp jumps in intravesical pressure and impaired storage function of the bladder. Detrusor hypotonia is characterized by decreased sensitivity of the bladder wall, its overflow, and an increase in urine pressure in its lumen above critical values. Detrusor-sphincter dyssynergia is a disruption of the synchronous functioning of the detrusor and sphincter apparatus, leading to functional IVO during urination.

With age, there is a tendency for the incidence of primary vesicoureteral reflux to decrease and the incidence of secondary vesicoureteral reflux to increase. At the same time, the incidence of regression of primary vesicoureteral reflux is inversely related to the degree of vesicoureteral reflux. At degrees I-II of vesicoureteral reflux, its regression is observed in 80%, and at III - only in 40% of cases. An explanation for this is given by the theory of "maturation" of PMS, which found supporters later. The essence of the theory is that with the development of the child, a physiological transformation of PMS occurs: the intravesical section of the ureter lengthens, its diameter decreases relative to its length, and the angle of entry into the bladder changes.

According to S.N. Zorkina (2005), more than 25% of patients with initial forms of vesicoureteral reflux (I and II degrees) suffer from chronic pyelonephritis, and with an increase in the degree of vesicoureteral reflux, the frequency of pyelonephritis also progressively increases, reaching 100% at IV and V degrees.

In the literature of recent years, the term "chronic pyelonephritis", considered as one of the complications of vesicoureteral reflux, under the influence of new factors is increasingly replaced by the term refluxogenic nephropathy (reflux nephropathy). The authors explain the change of name by the change in ideas about the pathogenesis of morphofunctional changes in the kidneys in patients with vesicoureteral reflux. In their works, these scientists prove that the development of inflammatory, dysplastic and fibrous lesions of the renal parenchyma in patients with vesicoureteral reflux is not a complication associated with the penetration of infection into the renal parenchyma, but an obligatory component of this pathological condition, characterized by regurgitation of urine from the bladder.

The presence of sclerotic changes in the renal parenchyma occurs in 60-70% of patients with vesicoureteral reflux, with the highest risk of nephrosclerosis development observed in the first year of life and amounting to 40%. In newborns, renal insufficiency is diagnosed in 20-40% of cases of vesicoureteral reflux development, which indicates its prenatal pathogenesis. Thus, Rolleston et al. (1970) found that 42% of infants with severe vesicoureteral reflux already had signs of nephrosclerosis at the time of the initial examination.

According to the European Association of Urologists for 2006, reflux nephropathy is the most common cause of childhood arterial hypertension. Anamnestic studies have shown that 10-20% of children with reflux nephropathy develop arterial hypertension or terminal renal failure. Ahmed gives higher figures. According to him, as a result of kidney scarring due to urinary tract infection, 10% develop terminal chronic renal failure and 23% develop nephrogenic arterial hypertension.

Vesicoureteral reflux is the cause of acute pyelonephritis in children. Thus, for more than 25 years, vesicoureteral reflux has been recorded in 25-40% of children with acute pyelonephritis.

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