Recurrent cystitis in women: causes and pathogenesis

More than 95% of uncomplicated urinary tract infections are caused by a single microorganism. The most frequent pathogens are Gram-negative enterobacteria, usually Escherichia coli (70-95% of cases). The second most frequent pathogen is Staphylococcus saprophyticus (5-20% of all uncomplicated urinary tract infections), which is more often isolated in young women. Significantly less frequent causes of recurrent cystitis in women are Klebsiella spp. Or Proteus mirabilis. In 1-2% of cases, pathogens caused by uncomplicated urinary tract infections are Gram-positive microorganisms (Group B and D streptococci). The causative agents of cystitis can be mycobacteria tuberculosis and rarely pale treponema. However, 0.4-30% of cases in the urine of patients do not show any pathogenic microflora. In the etiology of urethritis and cystitis in women, the role of urogenital infection (Chlamidia trachomatis, Ureaplasma urealiticum, Neisseria gonorrhoeae, Mycoplasma hominis, Trichomonas vaginalis) is unquestionable. There is scientific evidence that, for example, U. Urealiticum, as a rule, realizes its properties when associated with other pathogenic (opportunistic) microorganisms, and the development of the inflammatory process depends on the massiveness of dissemination. In this regard, great importance attaches to data indicating the colonization of the urogenital organs in approximately 80% of healthy women of the sexually active age U. Urealiticum, which, apparently, can in some cases realize pathogenic properties. Ureaplasma infection serves as a kind of conductor, contributing to contamination of the urino-genital organs by conditionally pathogenic microorganisms (endogenous and exogenous) and realizing the properties of the latter.

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

• anatomical and physiological features of the female body - short and wide urethra, proximity to natural infection reservoirs (rectum, vagina);
• frequent accompanying gynecological diseases inflammatory processes in the vagina, hormonal disorders leading to dysbiosis of the vagina and reproduction in it of pathogenic microflora;
• genetic predisposition;
• the ability of gram-negative microorganisms causing the infectious process in the urethra and bladder to adhere to the cells of the epithelium with the help of pimples and villi;
• the frequency of sexual acts and the characteristics of contraceptives used.

The most complete classification is the classification of AV Lyulko cystitis, taking into account the etiology and pathogenesis, the degree of prevalence of the inflammatory process, the clinical picture of the disease and the morphological changes in the wall of the bladder.

On features of the pathogenesis of recurrent cystitis in women:

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

With the flow:

• acute;
• chronic (latent, recurrent).

By the prevalence of the inflammatory process:

• diffuse:
• focal (cervical, trigonitis).

Depending on the nature and depth of morphological changes:

• Acute:
  • catarrhal;
  • hemorrhagic;
  • granulation:
  • fibrinous:
  • ulcerative;
  • gangrenous;
  • phlegmonous.
• Chronic:
  • catarrhal;
  • ulcerative;
  • polyposis;
  • cystic;
  • inlaid;
  • necrotic.

The following classification of chronic cystitis is suggested.

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

[1], [2], [3], [4], [5]

Interstitial cystitis

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

One explanation for the more frequent infection of the bladder and the development of cystitis in women consider the peculiarity of their urination: rotational hydrodynamics of urine at the time of emptying the bladder can be accompanied by infection of the bladder (urethrovesic reflux).

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

The violation of the barrier properties of the mucous membrane of the genital organs, caused by various causes of urogenital infections, accompanying gynecological diseases, leads to bacterial colonization of these zones and creates conditions for the formation of an infection reservoir at the external opening of the urethra, and often in the distal part of it. Given the presence of concomitant infectious diseases of female genitalia, we can assume the probability of decompensation of factors of anti-infective resistance and the creation of conditions for the invasion of microorganisms, including U. Urealiticum, into the bladder.

The invasion of bacteria in 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 a significant resistance, which is due to a number of antibacterial mechanisms that constantly and effectively function in healthy women. The urothelium produces and secretes onto the surface a mucopolysaccharide substance covering the surface of the cell and forming a protective layer that acts as an antiadhesive factor. The formation of this layer is a hormonal-dependent process: estrogens affect its synthesis, progesterone on its release by epithelial cells. Normally, urine has a bacteriostatic effect, which is due to low pH, high urea concentration, and osmolarity. In addition, urine may contain specific or nonspecific growth inhibitors of IgA, G and sIgA.

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

• co-existence with the host cell by a combined glycocalysis (persistence);
• damage to the glycocalyx and contact with the cell membrane.

Adhered microorganisms are usually not detected, since they do not create colonies on nutrient media. That is why there is an underestimation of their participation in the development of recurrent infections. Uropathogenic strains of Escherichia coli contain protein structures (adhesins, pilins) responsible for the adhesive ability of bacteria. By means of pili, microorganisms bind to each other and transmit genetic material - plasmids, with which all virulence factors are transported. Uropathogenic strains of Escherichia coli differ with adhesins (fimbrial and non-fimbrial). Multiple types of adhesins (P, S, AFA) are tropic to various types of epithelium. Strains of Escherichia coli - carriers of adgezin R firmly fuse with transitional and flat epithelium of the urethra and demonstrate tropism to the parenchyma of the kidney. One strain of uropathogenic E. Coli can synthesize genetically different adhesins. The variety of protective properties of bacteria determines the possibility of persistence of microorganisms in the human genitourinary system. Genetic factors of a macroorganism determine predisposition to a recurrent urinary tract infection and the presence of specific receptors for various microorganisms on the mucous membranes.

In women with "vaginalisation of the urethra" during sexual intercourse, the epithelial layer of the urethra can be disturbed, which creates conditions for colonization by the microflora of the intestine and the vagina. To exclude anomalies in the location of the external opening of the urethra, the patient should be examined by a gynecologist. Clinical examination also includes assessment of the state of the mucous membrane of the vestibule vestibule, the external opening of the urethra, the determination of its topography with the O'Donnel sample (the index and middle fingers of the hand introduced into the introitus are laterally dilated and simultaneously pressurize the back wall of the vagina). At the same time, the rigidity of the remnants of the hymen ring, which determine the intravaginal displacement of the urethra during sexual intercourse, and its expansion (the factor of constant infection of the lower urinary tract, contributing to the development and frequent recurrence of chronic cystitis) is evaluated. Palpatory assessment of the condition of the urethra and paraurethral tissues.

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

Unreasonableness and irrationality of antibacterial therapy are factors that lead to process chronicization and impaired immunoregulatory mechanisms. Re-administration of antibiotics of one group leads to the formation of resistant strains.

Quite often, the occurrence of cystitis is associated with catheterization of the bladder after surgery. Particular attention should be paid to the danger of too frequent, produced without sufficient indications of the procedure. Intravesical manipulations (for example, urinary catheter collection for bacteriological analysis) can also lead to the development of a hard-to- treat chronic cystitis caused by a polymicrobial hospital microflora.

Chronic cystitis can occur against a background of neoplasms of the bladder, central paresis, stricture of the urethra, tuberculosis, and previous injuries.

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