Causes and pathogenesis of vesicoureteral reflux

The bladder-ureteral reflux causes a variety.

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

• persistent yawning of the mouth ("funnel-shaped" configuration of the ureter's mouth); 
• the location of the mouth of the ureter outside the Lieto triangle (dystopia of the ureteric orifice);
• short submucosal tunnel of the intravesical ureter; 
• doubling of the ureter; 
• paraurectal diverticulum.

The main causes of vesicoureteral reflux of the secondary form:

• organic IVO (valve or urethral stricture, sclerosis of the neck of the bladder, stenosis of the external opening of the urethra);
• dysfunction of the bladder (GMS, detrusor-sphincter discoordination);
• inflammation in the region of the Ljeto triangle and the ureteral orifice (with cystitis); 
• wrinkling of the bladder ("microcystis"); 
• iatrogenic lesions of the zone of the Ljeto triangle and the ureteral mouth (operations with dissection of the detrusor smooth muscle or the effect on the ureteral ureter: ureterocystoanastomosis, buoyage of the ureteral orifice, dissection of the ureterocele, etc.).

It is impossible to understand the causes of vesicoureteral reflux without presentation of the normal structure of the vesicoureteral anastomosis. Anatomically closing function of the vesicoureteral anastomosis is achieved due to the ratio of the length and width of the intravesical ureter (5: 1), obliquely passing the ureter through the wall of the bladder. A long submucosal tunnel is a passive element of the ureterovezic valve. The active element of the valve mechanism is represented by the musculoskeletal apparatus of the ureter and the Lieto triangle, which, when detrusor is contracted, closes the mouth.

The causes of nonphysiological urine flow include pathological conditions leading to disruption of the closure mechanism of the vesicoureteral anastomosis and high intravesical fluid pressure (urine). The first can include congenital malformations of the vesicoureteral anastomosis and an inflammatory process in the surface of the deep or deep triangle of the bladder ( cystitis ). Violating the function of detrusor or directly the vesicoureteral anastomosis.

Anomalies of the vesicoureteral anastomosis often result from the incorrect development of the ureteral outgrowth of the wolf's duct at the 5th week of embryogenesis. Types of anomalies of the vesicoureterial anastomosis:

• a wide, constantly gaping form of the ureter's mouth:
• location of the ureteral orifice outside the zone of the urinary bladder triangle (lateroposition):
• complete absence or shortening of the submucosal tunnel of the vesicoureterial anastomosis:
• violation of the morphological normal structure of the vesicoureteral anastomosis (dysplasia).

The loss of the closing function of the vesicoureteral anastomosis occurs in the inflammation of the wall of the bladder or the zone of the vesicoureterial anastomosis. Most often, secondary vesicoureteral reflux is a consequence (complication) of the bullous (granular) or fibrinous form of cystitis. Infection of the urinary system occurs in 1-2% of boys and 5% of girls. More often urinary ways are colonized by a conditionally-pathogenic (intestinal) flora, among which the main place is occupied by E. Coli (40-70%).

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

ON. 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 "breakdown of the antireflux apparatus of the vesicoureterial anastomosis" and subsequent sclerotic and atrophic changes in the intramural ureter. On the other hand, prolonged chronic inflammation in the neck of the bladder often leads to stenosis of the urethra and disruption of urodynamics, which also leads to the onset of secondary vesicoureteral reflux.

Normally, the vesicoureteral anastomosis is able to withstand the intravesical pressure of the liquid in 60-80 cm of water. Art. High hydrostatic pressure is a consequence of IVO or functional disorders of the bladder. IVO develops in the valves of the posterior part of the urethra in boys, congenital sclerosis of the sheiks of the bladder (Marion's disease), stenosis of the external opening of the urethra in girls, scarring phimosis.

Neurogenic bladder dysfunction occurs in 20% of children aged 4-7 years. By the age of 14, the number of people suffering from neurogenic bladder dysfunction is reduced to 2%. Neurogenic bladder dysfunction manifests itself as an irritative or obstructive symptomatology. The main forms of neurogenic dysfunction of the bladder: bladder hyperactivity, detrusor hypotension and detrusor sphincter dissynergy. In these conditions, vesicoureteral reflux is also considered secondary and is a consequence of increased fluid pressure in the bladder. Hyperactivity of the bladder is characterized by sharp jumps in intravesical pressure and impaired memory function of the bladder. Hypotension detrusora is characterized by a decrease in the sensitivity of the wall of the bladder, its overflow and the increase in the pressure of urine in its lumen is above the critical figures. Detruzor-sphincter dissynergy is a violation of the synchronous work of the detrusor and the sphincter apparatus, leading to a functional IVO in case of a micturition.

With age, there is a tendency to a decrease in the incidence of primary and an increase in the frequency of secondary vesicoureteral reflux. In this case, the regression frequency of the primary vesicoureteral reflux is inversely related to the degree of vesicoureteral reflux. At I-II degree of vesicoureteral reflux its regression is noted in 80%. And at III - only in 40% of cases. The explanation of this is given by the theory of "PTC maturation", which found supporters later. The essence of the theory is that. That with the development of the child there is a physiological transformation of the PMS: the intravesical section of the ureter lengthens, its diameter decreases with respect to the length and the angle of the bladder

According to S.N. Zorkna (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% for IV and V degrees.

In the literature of recent years the term "chronic pyelonephritis", considered as one of the complications of vesicoureteral reflux, is increasingly replaced by the term refluxogenic nephropathy (reflux-nephropathy) under the influence of new factors. The authors explain the change of name by changing the concept of 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 infection in the renal parenchyma but an obligatory component of this pathological condition characterized by urinary bladder regurgitation.

The presence of sclerotic changes in the kidney parenchyma occurs in 60-70% of patients with vesicoureteral reflux, with the greatest risk of developing nephrosclerosis observed in the first year of life and is 40%. In newborns, renal failure is diagnosed in 20-40% of cases of development of vesicoureteral reflux, which indicates its prenatal pathogenesis. So. 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 in 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. Higher figures lead Ahmed. According to him, as a result of renal scarring with infection of the urinary system, 10% develop terminal chronic renal failure and 23% have nephrogenic hypertension.

Bladder and ureter reflux is the cause of acute pyelonephritis in children. So, for more than 25 years vesicoureteral reflux has been registered in 25-40% of children with acute pyelonephritis.

[1], [2], [3], [4], [5], [6], [7], [8], [9]