Pathogenesis of urinary tract infections

Routes of urinary tract infection

Three routes of infection are discussed for urinary tract infection: ascending (or urinogenous), hematogenous, and lymphogenous.

The urinogenic (or ascending) route of infection is most common in children. The ascending route of infection is facilitated by colonization of the vaginal vestibule, periurethral area, preputial sac and distal parts of the urethra with uropathogenic microorganisms. Normally, colonization of uropathogenic flora in girls is prevented by normal vaginal microflora, represented mainly by lactobacilli producing lactic acid (reduce vaginal pH) and hydrogen peroxide, which creates an unfavorable environment for the growth of uropathogenic microbes. Violation of the vaginal microflora may be associated with estrogen deficiency, decreased local secretion of IgA. With recurrent urinary tract infection, the level of secretory IgA decreases sharply, and the secretion of lysozyme is disrupted. In newborns, the concentration of secretory IgA in urine is extremely low, which serves as a risk factor for the development of urinary tract infection in the neonatal period.

Penetration of microbes from the periurethral area into the urethra is normally hampered by the urine flow. Accordingly, the more frequent and abundant the urination, the lower the risk of ascending urinary tract infection. A shorter urethra in girls and turbulence of the urine flow during urination facilitate the penetration of bacteria into the bladder and are among the main reasons for the higher frequency of urinary tract infections in girls. Along with urination and local immunity disorders, early sexual activity can facilitate the penetration of microorganisms into the urethra. During sexual intercourse, the external opening of the urethra is subject to mechanical action, facilitating the penetration of uropathogenic microbes that colonize the vaginal area.

In countries where circumcision is traditional, the incidence of urinary tract infections in boys is very low.

The hematogenous route of infection is most likely in bacterial infections, sepsis, and apostematous nephritis. The presence of the lymphogenous route of infection is controversial. There is a hypothesis about the lymphogenous migration of microorganisms associated with the process of their translocation from the intestine to the mesenteric lymph nodes and bloodstream.

Development of infection in the bladder

Penetration of uropathogenic bacteria into the urinary bladder is not always accompanied by the development of an inflammatory process. Although urine is a good nutrient medium, in healthy children the urinary tract is sterile except for the distal part of the urethra. Along with the mechanical washing out of microbes by the urine flow, there are a number of protective factors that ensure the safety of the bladder mucosa. The cellular layer of the transitional epithelium is covered with a film of mucopolysaccharide (glycosaminoglycan with hydrophilic properties). The glycosaminoglycan layer prevents contact of bacteria with the uroepithelium, complicates their adhesion. Exogenous mechanical and chemical effects destroy the mucopolysaccharide layer. However, within 24 hours this layer is able to recover, maintaining its protective effect.

Normally, bacteria in the bladder are destroyed within 15 minutes. Local protection of the organ is sharply reduced if the amount of residual urine increases. It is known that the concentration of bacteria in the bladder decreases several times with frequent emptying, which is one of the ways to prevent urinary tract infections. However, in young children (up to 4-5 years old), a physiological inability to completely empty the bladder is noted. Incomplete emptying of the bladder is often observed against the background of chronic constipation.

The antimicrobial properties of urine are due to its high osmolarity, low pH, high content of urea and organic acids. These properties are significantly less pronounced in infants, which contributes to increased susceptibility to urinary tract infections. Uromucoids (e.g., Tamm-Horsfatt protein) and oligosaccharides contained in normal urine prevent adhesion of mannose-sensitive strains of E. coli to the uroepithelium.

Microorganisms can penetrate into the bladder, bypassing the urethra, in the presence of developmental defects (for example, vesicovaginal and vesicointestinal fistulas).

Development of infection in the ureters and renal parenchyma

Normally, the penetration of bacteria into the ureters and their ascent to the renal pelvis is prevented by the closure of the ureteral orifices and their distally directed peristalsis. Violation of these factors and any other variants of disorders of normal urodynamics leading to dilation of the ureters facilitate the ascending transport of microorganisms.

The development of infection in the renal parenchyma is accompanied by the synthesis of antibacterial antibodies directed against O- and K-antigens and P-fimbriae of E. coli. The concentration of antibodies in the blood serum is directly related to the severity of inflammation and the formation of foci of renal parenchyma shrinkage. Along with the synthesis of antibodies, phagocytosis is activated. As a result of intravascular aggregation of granulocytes and edema, local ischemia may develop, leading to the formation of sclerosis. An increase in the concentration of IgG and IgA stimulates the formation of complement, which in turn enhances the activity of inflammatory mediators. Local inflammation in the renal parenchyma prevents the spread of infection from the site of its development. In the lumen of the renal tubules, lysozyme and superoxidase are released under the influence of inflammation, leading to the formation of oxygen radicals that are toxic not only for bacteria, but also for tubular cells.

The renal papillae and medulla are most susceptible to the microbial inflammatory process. This is explained by the lower intensity of blood flow, lower pH, higher osmolarity and higher concentration of ammonium compared to the cortex. The listed factors create favorable conditions for bacterial growth and suppress leukocyte chemotaxis.

It is known that in newborns, who are not capable of full immune responses, the infectious process in the renal parenchyma tends to generalize with a septic nature of the course; low values of renal blood flow in this age group predispose to the development of renal shrinkage.

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