Pathogenesis of urinary tract infections

Ways of infection of the urinary tract

Discuss 3 ways of infection with urinary tract infection: ascending (or urinogenic), hematogenous and lymphogenic.

The urinogenic (or ascending) path of infection is most common in children. The upstream pathway of infection is facilitated by colonization with uropathogenic microorganisms of the vestibule vestibule, periurethral area, preputial sac and distal sections of the urethra. In normal colonization, the uropathogenic flora in girls is prevented by normal vaginal microflora, represented mainly by lactobacilli producing lactic acid (lowering the 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 a deficiency of estrogens, a decrease in local secretion of IgA. With a recurrent urinary tract infection, the level of secretory IgA is sharply reduced, the secretion of lysozyme is disturbed. In newborns, the concentration of secretory IgA in the urine is extremely low, which is a risk factor for urinary tract infection in the neonatal period.

Penetration of microbes from the periurethral area into the urethra is normally impeded by the flow of urine. Accordingly, the more frequent and abundant urination, the lower the risk of ascending infection of the urinary tract. The shorter urethra in girls and the turbulence of urine flow at the time of urination facilitate the entry of bacteria into the bladder and are one of the main causes of a higher incidence of urinary tract infection in girls. Along with impaired urination and local immunity, the penetration of microorganisms into the urethra can be facilitated by early sexual activity. In the process of sexual intercourse, the external opening of the urethra is subjected to mechanical action, facilitating the penetration of uropathogenic microorganisms colonizing the vaginal area.

In countries where circumcision is traditionally considered, the incidence of urinary tract infection in boys is very low.

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

Development of infection in the bladder

The penetration of uropathogenic bacteria into the bladder is not always accompanied by the development of the 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 of microbes by the current of urine, there are a number of protective factors that ensure the preservation of the mucous membrane of the bladder. The cell layer of the transitional epithelium is covered with a film of mucopolysaccharide (glycosaminoglycan having hydrophilic properties). The glycosaminoglycan layer interferes with the contact of bacteria with uroepithelium, making their adhesion difficult. Exogenous mechanical and chemical effects destroy the mucopolysaccharide layer. However, within a day this layer is able to recover, preserving its protective effect.

Normally, in the bladder, bacteria are destroyed within 15 minutes. Local organ protection decreases sharply 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 serves as one of the ways to prevent infection of the urinary tract. However, in infants (up to 4-5 years), a physiological inability to completely empty the bladder is noted. Incomplete emptying of the bladder is often observed against a background of chronic constipation.

Antimicrobial properties of urine are provided by its high osmolarity, low pH, high content of urea and organic acids. These properties are much less pronounced in infants, which contributes to increased susceptibility to urinary tract infection. Uromucoids (eg, Tamm-Horsfatt protein) and oligosaccharides in normal urine interfere with the adhesion to the uroepithelium of mannose-sensitive strains of Escherichia coli.

Microorganisms can penetrate into the bladder, bypassing the urethra, in the presence of malformations (for example, vesicovaginal and vestibular fistula).

Development of infection in the ureters and renal parenchyma

Normally, the penetration of bacteria into the ureters and their ascent to the 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 dilatation of 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 E. coli p-fimbria . The concentration of antibodies in the serum has a direct relationship with the severity of inflammation and the formation of foci of shrinking of the renal parenchyma. Along with the synthesis of antibodies, phagocytosis is activated. As a result of intravascular aggregation of granulocytes and edema, it is possible to develop local ischemia leading to the formation of sclerosis. Increasing the concentration of IgG and IgA stimulates the formation of complement, which in turn intensifies the activity of inflammatory mediators. Local inflammation in the renal parenchyma prevents the spread of infection from the focus of its development. In the lumen of the renal tubules under the influence of inflammation, lysozyme and superoxidase are released, leading to the formation of oxygen radicals, toxic not only for bacteria, but also for tubular cells.

The kidney papillae and the cerebral layer are most susceptible to the microbial-inflammatory process. This is explained by the lower blood flow intensity, lower pH, greater osmolarity, and higher ammonium concentration compared to the cortical zone. These factors create favorable conditions for bacterial growth and suppress leukocyte chemotaxis.

It is known that in infants who are not capable of full-fledged immune responses, the infectious process in the renal parenchyma is prone to generalization with septic flow, low values of renal blood flow in this age group predispose to the development of shrinkage of the kidneys.

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