Hemorrhagic cystitis

What is the difference between hemorrhagic cystitis and ordinary inflammation of the bladder? The main difference is in hematuria - the appearance of blood in the urine with urination. And this indicates a significant depth of damage to the multilayered epithelium (urothelium) of the mucosa of the inner walls of the bladder, as well as the spread of the destructive process to the endothelium of the capillaries of its microcirculatory bed.

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

Epidemiology

Annually about 150 million people are affected by bladder and urinary tract infections.

According to research, infectious hemorrhagic cystitis in women occurs much more often than in men. Especially in women during the menopause, because of the decline in the level of estrogen, the protective properties of the vaginal flora decrease.

Hemorrhagic cystitis in newborns in two thirds of cases is associated with the presence of untreated urogenital infections in the mother.

Also, hemorrhagic cystitis develops in almost 6% of patients who underwent bone marrow transplantation and received high doses of Cyclophosphamide or Ifosfamide.

[6], [7], [8], [9], [10], [11]

Causes of the hemorrhagic cystitis

To date, the causes of hemorrhagic cystitis, defining its types, are divided into infectious and non-infectious.

In most cases, bacterial acute hemorrhagic cystitis occurs due to infection of the bladder with uropathogenic Escherichia coli Escherichia coli (UPEC) strains, Proteus vulgaris, opportunistic Klebsiella oxytoca bacteria and Staphylococcus saprophyticus saprophytic.

The pathogenesis of UPEC injury is associated with the ability of Escherichia (representing the synanthropic intestinal flora, but found in the urinary tract) to act as opportunistic intracellular pathogens. With the help of adhesion organelles, bacteria enter the cells and colonize the urethra and bladder mucosa; here they feed on the iron compounds extracted from the cells and produce toxins-erythrocyte-destroying hemolysin and receptor-mediated endocytosis-catalyzing cytotoxic necrotizing factor 1 (CNF1), which causes the response of effector cells of the urothelium and inflammatory responses.

Often, infectious hemorrhagic cystitis in women is provoked by ureaplasma, mycoplasma, chlamydia, gardnerella, gonococci, trichomonads. But primary fungal cystitis is rare and, as a rule, it is associated with the treatment of bacterial cystitis: suppression of commensal vaginal microflora with antibiotics allows unhindered reproduction of Candida fungi and lactobacilli.

Against the background of inflammation of the prostate gland can develop hemorrhagic cystitis in men of the older age category. It is often provoked by an unsuccessful catheterization of the bladder and subsequent infection.

Viral hemorrhagic cystitis in children, as well as hemorrhagic cystitis in newborns, is most often associated with adenovirus serotypes 11 and 21 of subgroup B. Although this disease may be the result of activation of latent poliomyavirus BK (Human polyomavirus 1). According to the latest version of Virus Taxonomy, the BK virus infected most people, and in childhood it initiates respiratory diseases and acute cystitis. By the way, this virus in a latent form is preserved throughout life (in the tissues of the urino-genital organs and pharyngeal tonsils).

Reactivation of "sleeping" poliomyavirus VK occurs due to some form of immunosuppression: in old age, with congenital immunodeficiency in children, acquired immunodeficiency syndrome (AIDS) in adults, in women during pregnancy, which can be associated with hemorrhagic cystitis in pregnancy. Also, the virus is activated during bone marrow transplantation and allogeneic stem cells when drugs are used to suppress the immune system. Studies have shown that, after bone marrow transplantation, virus-induced hemorrhagic cystitis in children and adolescents is the most common complication.

Noninfectious causes of hemorrhagic cystitis

According to urologists, chronic hemorrhagic cystitis of non-bacterial etiology can develop due to the presence in the bladder of concrements - especially urate stones in urine acid diathesis - when the bladder mucosa is injured and the lesions become deeper under the influence of excessively acidic urine. Such a hemorrhagic cystitis is called by many domestic specialists ulcerative.

Also, such types of hemorrhagic cystitis as radiation (radiation) or chemically induced cystitis are not associated with infection. Radiation hemorrhagic inflammation of the bladder mucosa develops after treatment of malignant tumors localized in the small pelvis. In this case, pathogenesis is due to the fact that irradiation causes discontinuities in DNA chains leading to the activation of DNA repair and apoptosis repair genes. In addition, the radiation penetrates into the deeper layers of the muscles of the bladder, which reduces the impermeability of the walls of the vessels.

Chemically induced hemorrhagic cystitis is the result of intravenous injection of anticancer drugs-cytostatics, in particular, Ifosfamide (Holoxan), Cyclophosphamide (Cytoforsphan, Endoxan, Clafen, etc.) and to a lesser extent - Bloomycin and Doxorubicin.

Thus, the metabolism of cyclophosphamide in the liver leads to the formation of acrolein, which is a toxin and destroys the tissue of the wall of the bladder. Severe inflammation of the bladder, which occurs as a complication of chemotherapy for cancer patients, is called refractory (difficult to treat) hemorrhagic cystitis.

Hemorrhagic cystitis in women - in particular, the chemical - can develop if you get a means for intravaginal application through the urethra in the bladder. This happens when the vagina is syringed with methyl violet (Gentianviolet) antiseptic for the treatment of vaginal candidiasis or spermicide, for example, Nonoxynol.

[12], [13], [14], [15]

Risk factors

The main risk factors for the development of hemorrhagic cystitis are associated with a decrease in the body's immune defenses; the presence of latent urogenital infections and oncological diseases; stagnation of urine and urolithiasis; thrombocytopenia (low platelet count in the blood); violation of hygiene of the urino-genital organs and non-compliance with aseptic norms in gynecological and urological manipulations.

The risk of infection of the urinary tract and bladder in children is associated with vesicoureteral reflux (abnormal movement of urine) and constipation.

[16], [17], [18], [19], [20], [21],

Symptoms of the hemorrhagic cystitis

Usually the first signs of hemorrhagic cystitis are manifested by pollakiuria - more frequent urination with a simultaneous decrease in the volume of excreted urine. Almost simultaneously, such a characteristic sign of the initial stage of inflammation joins as multiple false urges to empty the bladder (including at night), as well as burning and acute soreness at the end of urination.

In addition, the following clinical symptoms of hemorrhagic cystitis are noted: unpleasant sensations in the pubic region; giving back and groin pain in the small pelvis; turbidity of the secretion of urine, a change in its color (from pink to all shades of red) and odor. Often lost control of the bladder (may be incontinence).

The general state of health worsens - with weakness, a decrease in appetite, fever and fever.

If at a certain stage of the disease the patient experiences difficulty urinating, this indicates that the bladder outlet is blocked by blood clots (tamponade).

[22], [23]

Complications and consequences

The main consequences and complications of hemorrhagic cystitis of any etiology include:

• violation of the outflow of urine (due to the blood clot mentioned above) can lead to urosepsis, rupture of the bladder and kidney failure;
• violation of the integrity of blood vessels microcirculatory bed of the bladder threatens blood loss and the development of iron deficiency anemia, especially if patients have chronic hemorrhagic cystitis;
• damaged areas of urothelium can become an "entrance gate" for infections and ensure the ingress of bacteria into the systemic circulation;
• open ulcers on the inner surfaces of the bladder often lead to a permanent scarring of its lining and sclerotic changes in the walls - with a decrease in size and deformation of the shape of the bladder.

[24], [25], [26], [27], [28]

Diagnostics of the hemorrhagic cystitis

Diagnosis of hemorrhagic cystitis by urologists is carried out, but gynecologists may be required when hemorrhagic cystitis occurs in women.

Such analyzes are necessary:

• general urine analysis;
• microbiological analysis of urine (using PCR-sequencing of urine - to identify the type of infectious agent and its resistance to antibacterial drugs);
• clinical blood test;
• blood test for STDs;
• A swab from the vagina and cervix (for women);
• a smear from the urethra (for men);

The instrumental diagnostics is used: ultrasound of the bladder and all organs of the small pelvis, cystoscopy, urethroscopy.

To clarify the functional state of the muscular layer of the bladder in the chronic form of hemorrhagic cystitis, specialists can examine urodynamics using uroflowmetry or electromyography of the bladder.

[29], [30], [31], [32]

Differential diagnosis

Differential diagnosis is designed to distinguish hemorrhagic cystitis from hematuria, which can accompany inflammation of the urethra (urethritis); tumors of the bladder or urinary tract; adenoma of the prostate (in men) or endometriosis (in women); pyelonephritis, focal proliferative glomerulonephritis, polycystic kidney disease, etc.

Treatment of the hemorrhagic cystitis

Complex treatment of hemorrhagic cystitis is aimed at the causes of the disease, as well as to alleviate its symptoms.

When the bacterial origin of the disease is necessarily prescribed antibiotics for hemorrhagic cystitis. The most active fluoroquinolones, for example, Norfloxacin (other trade names are Nolycin, Bactinor, Norbaktin, Normaks, Urobacil) and Ciprofloxacin (Ciprobai, Ziplox, Cyprinol, Ciproxine, Ciprolet, etc.).

Norfloxacin (in tablets of 400 mg) is recommended to take one tablet twice a day for one to two weeks. The drug can cause attacks of nausea, decreased appetite, diarrhea and general weakness. Norfloxacin is contraindicated in cases with kidney problems, epilepsy, children under 15 years of age and pregnant.

The bactericidal effect of ciprofloxacin (in tablets of 0.25-0.5 g and in the form of a solution for infusions) is stronger. Recommended dosage: twice daily for 0.25-0.5 g (in severe cases, the drug is administered parenterally). Ciprofloxacin has similar contraindications, and its side effects are manifested by skin allergy, abdominal pain, dyspepsia, a decrease in leukocytes and blood platelets, as well as increased sensitivity of the skin to UV rays.

Phosphomycin-containing trometamol antibiotic Fosfomycin and its synonyms Phosphoral, Fosmicin, Urofoscin, Urophosfabol, Ekofomural or Monural with hemorrhagic cystitis is also effective due to the predominant concentration in the tissues of the kidneys. The drug is prescribed 300 mg once a day (the granules are dissolved in 100 ml of water) - two hours before a meal. Children Fosfomycin can be used after five years: one dose at a dose of 200 mg. Side effects can be in the form of hives, heartburn, nausea and diarrhea.

See also - Tablets from cystitis

The most important component of the treatment of hemorrhagic cystitis is the removal of a blood clot from the bladder. It is removed by inserting a catheter into the bladder and by continuous instillation (irrigation) of the bladder cavity with sterile water or saline solution (urologists note that water is preferable to sodium chloride solution, as it dissolves clots better).

If hematuria persists after removal of the clot, irrigation can be done with Carboprost or a solution of silver nitrate. In severe cases, 3-4% formalin solution (which is instilled under anesthesia and cystoscopic control) can be used intravesically, followed by thorough irrigation of the bladder cavity.

To treat hemorrhagic cystitis, hemostatic drugs are used: aminocaproic and tranexamilic acid, Dicinone (orally), Etamsylate (parenterally). Vitamins - ascorbic acid (C) and phylloquinone (K) are necessarily prescribed.

Admissible physiotherapeutic treatment of radiation hemorrhagic cystitis is hyperbaric oxygenation (oxygen therapy), which stimulates cellular immunity, activates angiogenesis and regeneration of the tissues lining the bladder; causes narrowing of blood vessels and helps to reduce bleeding.

Operative treatment

When instillation of the cavity of the bladder with a catheter is not possible, resort to the endoscopic removal of the blood clot (cystoscopy) - under anesthesia, followed by the use of antibiotics. At the same time, cauterization of hemorrhagic sites (electrocoagulation or argon coagulation) can be performed to stop bleeding.

Operative treatment is most often required with refractory hemorrhagic cystitis. And besides cystoscopy with electrocoagulation, selective embolization of the hypogastric branch of the artery is possible. In extreme cases (with extensive scarring of the walls of the bladder and its deformation), cystectomy (removal of the bladder) with urinary diversion through the ileum (near the ileocecal valve), sigmoid colon or by percutaneous ureterostomy is indicated.

According to experts, cystectomy represents a significant risk of postoperative complications and mortality, since patients have already undergone radiation or chemotherapy.

Alternative treatment

Limited alternative treatment for hemorrhagic cystitis (which in most cases requires hospital stay) extends to the bacterial appearance of the disease.

This treatment with herbs that promote diuresis and relieve inflammation. It is recommended to take decoctions of diuretic medicinal plants: alternating tripartite, horsetail, meadow, field harness, meadow clover, crochet creeper, nettle nettle, bearberry, corn stigmas. Decoctions are prepared from the calculation - one and a half tablespoons of dry herbs for 500 ml of water (boil for 10-12 minutes); a decoction of 100 ml 3-4 times a day is taken.

Among the anti-inflammatory medicinal plants in urology, the most commonly used fruits are juniper, bearberry, a leaf of cranberries and a nettle white. You can mix all the plants in equal proportions, and to prepare medicinal herbal tea, brew a tablespoon of the mixture with three glasses of boiling water. Take recommended for 200 ml three times a day for 8-10 days.

Diet for hemorrhagic cystitis - see the publication Diet for cystitis

[33], [34], [35], [36], [37], [38], [39]

Prevention

Prevention of urinary tract infections and timely detection and treatment of latent urogenital infections, strengthening of immunity and the absence of bad habits will help to protect yourself from hemorrhagic cystitis, but do not guarantee 100% protection and can not be protected from a non-infectious disease.

To prevent the development of hemorrhagic cystitis in cancer chemotherapy, it is possible to use Mesna drug before starting treatment. However, the already begun refractory hemorrhagic cystitis Mesna will not prevail. The toxicity of antitumor agents mentioned in the article can also be minimized with the simultaneous use of the drug Amifostin (Etiol).

[40], [41], [42], [43]

Forecast

The prognosis of the outcome of inflammation of the bladder, accompanied by hematuria, depends on its cause, correctly diagnosed, adequate treatment and general condition of the body.

[44]