Recurrent cystitis in women - Causes and pathogenesis

More than 95% of uncomplicated urinary tract infections are caused by a single microorganism. The most common pathogens are gram-negative enterobacteria, usually Escherichia coli (70-95% of cases). The second most frequently detected pathogen is Staphylococcus saprophyticus (5-20% of all uncomplicated urinary tract infections), which is somewhat more often isolated in young women. Much less common causes of recurrent cystitis in women are Klebsiella spp. or Proteus mirabilis. In 1-2% of cases, the causative agents of uncomplicated urinary tract infections are gram-positive microorganisms (group B and D streptococci). Mycobacterium tuberculosis and, rarely, pale treponema can be causative agents of cystitis. However, in 0.4-30% of cases, no pathogenic microflora is detected in the urine of patients. Urogenital infection (Chlamidia trachomatis, Ureaplasma urealiticum, Neisseria gonorrhoeae, Mycoplasma hominis, Trichomonas vaginalis) undoubtedly plays a role in the etiology of urethritis and cystitis in women. There is scientific evidence that, for example, U. urealiticum, as a rule, realizes its properties in association with other pathogenic (opportunistic) microorganisms, and the development of the inflammatory process depends on the massiveness of dissemination. In this regard, data indicating colonization of the urogenital organs in approximately 80% of healthy women of sexually active age by U. urealiticum, which, apparently, can in some cases realize pathogenic properties, are of great importance. Ureaplasma infection serves as a kind of conductor, facilitating contamination of the urogenital organs with opportunistic microorganisms (endogenous and exogenous) and the realization of the properties of the latter.

Uncomplicated urinary tract infections are characterized by recurrence, which in 90% of cases is associated with reinfection. It has been established that 50% of women after an episode of cystitis develop a relapse within a year, 27% of young women have a relapse within 6 months, and 50% of patients have relapses more than three times a year. Such a high frequency of recurrence can be explained by the following factors:

• anatomical and physiological features of the female body - a short and wide urethra, proximity to natural reservoirs of infection (rectum, vagina);
• frequent concomitant gynecological diseases, inflammatory processes in the vagina, hormonal disorders leading to vaginal dysbiosis and the proliferation of pathogenic microflora in it;
• genetic predisposition;
• the ability of gram-negative microorganisms that cause an infectious process in the urethra and bladder to adhere to epithelial cells using fimbriae and villi;
• frequency of sexual intercourse and characteristics of the contraceptives used.

The most complete classification of cystitis is considered to be A.V. Lyulko's, which takes into account the etiology and pathogenesis, the degree of prevalence of the inflammatory process, the clinical picture of the disease and morphological changes in the wall of the bladder.

According to the peculiarities of the pathogenesis of recurrent cystitis in women:

• primary:
• secondary.
• chemical;
• thermal;
• toxic;
• drug;
• neurogenic;
• radiation;
• involutional;
• postoperative;
• parasitic:
• viral.

Downstream:

• spicy;
• chronic (latent, recurrent).

By prevalence of the inflammatory process:

• diffuse:
• focal (cervical, trigonitis).

Depending on the nature and depth of morphological changes:

• Spicy:
  • catarrhal;
  • hemorrhagic;
  • granulation:
  • fibrinous:
  • ulcerative;
  • gangrenous;
  • phlegmonous.
• Chronic:
  • catarrhal;
  • ulcerative;
  • polypous;
  • cystic;
  • incrusting;
  • necrotic.

The following classification of chronic cystitis is proposed.

• Chronic latent cystitis:
  • chronic latent cystitis with a stable latent course (absence of complaints, laboratory and bacteriological data, the inflammatory process is detected only endoscopically);
  • chronic latent cystitis with rare exacerbations (activation of inflammation of the acute type, no more than once a year);
  • latent chronic cystitis with frequent exacerbations (twice a year or more, like acute or subacute cystitis).
• Chronic cystitis (persistent) itself - positive laboratory and endoscopic data, persistent symptoms in the absence of a violation of the reservoir function of the bladder.
• Interstitial cystitis (IC) is a persistent pain syndrome, pronounced clinical symptoms, sometimes with a decrease in the reservoir function of the bladder.

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Interstitial cystitis

Interstitial cystitis is an independent nosological form that requires separate consideration.

One of the explanations for the more frequent infection of the bladder and the development of cystitis in women is considered to be the peculiarity of their urination: the rotational hydrodynamics of urine at the moment of emptying the bladder can be accompanied by infection of the bladder (urethrovesical reflux).

According to Russian researchers, up to 59% of women suffering from chronic non-specific lower urinary tract inflammation have signs of infravesical obstruction. In most cases, the obstruction zone is localized in the bladder neck and proximal part of the urethra. There are studies that show the role of fibroepithelial polyps that cause IVO, leading to secondary bladder diverticula, ureterohydronephrosis, chronic pyelonephritis in women with long-term cystitis. Chlamydia and mycoplasma can cause acute and chronic forms of cystitis, accompanied by proliferative changes in the mucous membrane. The experiment proved that the introduction of U. urealiticum into the bladder of rats causes the development of an inflammatory process, accompanied by the formation of struvite bladder stones and damage to the mucous membrane, mainly of a hyperplastic nature. In addition, the role of urogenital infections in the etiology of recurrent cystitis and non-obstructive pyelonephritis in women has been experimentally and clinically proven. According to some data, urogenital infections were detected by the PCR method in 83% of patients with pyelonephritis and in 72% of patients with recurrent cystitis. The concept of ascending infection of the bladder in women is confirmed by numerous foreign and domestic researchers.

Violation of the barrier properties of the mucous membrane of the genital organs, caused by various reasons, the presence of urogenital infections, concomitant gynecological diseases, leads to bacterial colonization of these zones and creates conditions for the formation of a reservoir of infection at the external opening of the urethra, and often in its distal section. Considering the presence of concomitant infectious diseases of the female genital organs, one can assume the likelihood of decompensation of anti-infective resistance factors and the creation of conditions for the invasion of microorganisms, including U. urealiticum, into the bladder.

Bacterial invasion into the bladder is not considered the main condition for the development of the inflammatory process, and this is confirmed by clinical and experimental studies. The bladder in women has significant resistance, which is due to a number of antibacterial mechanisms that are constantly and effectively active in healthy women. The urothelium produces and secretes a mucopolysaccharide substance onto the surface, covering the cell surface and forming a protective layer that acts as an anti-adhesive factor. The formation of this layer is a hormone-dependent process: estrogens affect its synthesis, progesterone affects its secretion by epithelial cells. Normally, urine has a bacteriostatic effect, which is due to a low pH value, a high concentration of urea and osmolarity. In addition, urine may contain specific or non-specific inhibitors of bacterial growth IgA, G and sIgA.

However, bacterial adhesion to uroepithelial cells is one of the important pathogenic factors in the development of urinary tract infection. It is realized in two ways:

• coexistence with the host cell by a united glycocalyx (persistence);
• damage to the glycocalyx and contact with the cell membrane.

Adherent microorganisms are usually not detected, since they do not create colonies on nutrient media. This is why their participation in the development of recurrent infections is underestimated. Uropathogenic strains of E. coli contain protein structures (adhesins, pilins) responsible for the adhesive ability of bacteria. Microorganisms bind to each other through fimbriae and transfer genetic material - plasmids, with which all virulence factors are transported. Uropathogenic strains of E. coli differ in adhesins (fimbrial and non-fimbrial). Various types of adhesins (P, S, AFA) are tropic to different types of epithelium. Strains of E. coli - carriers of adhesin P firmly grow together with the transitional and squamous epithelium of the urethra and demonstrate tropism to the renal parenchyma. One strain of uropathogenic E. coli can synthesize genetically different adhesins. The diversity of protective properties of bacteria determines the possibility of persistence of microorganisms in the human genitourinary system. Genetic factors of the macroorganism determine the predisposition to recurrent urinary tract infection and the presence of specific receptors for various microorganisms on the mucous membranes.

In women with "vaginalization of the urethra" during sexual intercourse, the epithelial layer of the urethra may be damaged, which creates conditions for its colonization by intestinal and vaginal microflora. To exclude abnormalities in the location of the external opening of the urethra, the patient should be examined by a gynecologist. Clinical examination also includes an assessment of the condition of the mucous membrane of the vestibule of the vagina, the external opening of the urethra, determining its topography with the O'Donnel test (the index and middle fingers of the hand, inserted into the introitus, are spread laterally and simultaneously apply pressure to the posterior wall of the vagina). At the same time, the rigidity of the remnants of the hymenal ring, causing intravaginal displacement of the urethra during sexual intercourse, as well as its expansion (a factor in the constant infection of the lower urinary tract, contributing to the development and frequent recurrence of chronic cystitis) are assessed. The condition of the urethra and paraurethral tissues is assessed by palpation.

In 15% of cases, frequent painful urination may be caused by vaginitis.

Unreasonableness and irrationality of antibacterial therapy are factors leading to chronicity of the process and disturbances of immunoregulatory mechanisms. Repeated prescription of antibiotics of the same group leads to the formation of resistant strains.

Quite often, the occurrence of cystitis is associated with catheterization of the urinary bladder after surgical interventions. Particular attention should be paid to the danger of too frequent procedures performed without sufficient indications. Intravesical manipulations (for example, taking urine with a catheter for bacteriological analysis) can also lead to the development of chronic cystitis, which is difficult to treat, caused by polymicrobial hospital microflora.

Chronic cystitis can occur against the background of neoplasms of the bladder, central paresis, strictures of the urethra, tuberculosis, and past injuries.

In chronic cystitis, all three layers of the bladder wall are usually involved in the pathological process, causing the latter to thicken sharply. The physiological capacity of the bladder is significantly reduced. As in acute cystitis, pathological changes occupy the Lieto triangle and the bottom of the bladder, localizing mainly around its mouth and neck.