What are urinary disorders? |

Causes and Symptoms

Diseases of the urinary tract represent one of the most common forms of infection by microorganisms. In the United States, the prevalence of urinary tract infections is a reflection of both gender and age. By the age of five, bacteriuria is found in approximately 4 to 5 percent of girls, which is about ten times the rate among boys. Infections are far more common among female adolescents and young women than among men, with a yearly prevalence of approximately 20 percent of American women in the age group of sixteen to thirty-five years accounting for approximately six million reported cases each year. Data regarding prevalence of infection varies depending on what definition of infection is used. The prevalence of infection among both men and women rises sharply among the elderly, often reflecting problems with aging, including enlargement of the prostate in men. Most infections are self-limiting, particularly among the young. If not treated properly, however, such infections have the potential to be more serious.

Normally, urine is free of microbial contamination. The much higher incidence of urinary tract infections in women reflects, to a large degree, the anatomical differences between males and females. In women, the close proximity of the
urethra to the rectum permits relatively easy access of intestinal flora to the urinary tract. Not surprisingly, most urinary infections are caused by enteric bacteria. The most common infectious agent, Escherichia coli, represents approximately 80 percent of the acquired infections of the urinary tract. Other bacterial genera of importance include Enterobacter, Klebsiella, and Proteus. Proteus infections may be of particular significance because colonization by that organism may lead to the deposition of urinary calculi (stones). Less often, Streptococcus faecalis or Pseudomonas aeruginosa may be involved; the latter can be a particular problem because of its high level of
drug resistance.

Urinary tract infections usually begin with entry of the organisms into the distal end of the urethra; the migration of microorganisms into the vagina may occur in a similar manner. Most bladder infections result from ascending movement of the microbial agents along the urethra into the urinary bladder. Inflammation of the urethra (urethritis) or urinary bladder (cystitis) results from a combination of microbial colonization and the host’s immune response to the infection. Often, such inflammation may be the first symptom of these infections.

Various factors appear to predispose certain individuals to urinary tract infections. Strains of E. coli that colonize the urethra appear to have a greater ability to adhere to the surface tissue. In particular, those strains that frequently ascend into the ureters or kidneys often possess unique types of fimbriae (filamentous structures), which promotes adherence to the epithelial cells that line the surface of the urinary tract; this bacterial structure may be of particular importance to the course of the infection, since the flushing action of urinary flow is a mechanism by which the body maintains the sterility of the urinary tract. Likewise, anything with the potential to interrupt micturition (urination), such as the presence of calculi or tumors, may predispose an individual to a urinary tract infection. Enlargement of the prostate gland in older men is a frequent cause of such problems. Among children, congenital abnormalities at the site of ureter entry into the bladder may result in a vesicoureteral reflux, or urine backflow, which may interfere with normal urine flow. Such abnormalities, which are not uncommon, are found in equal
numbers among both young boys and girls; they frequently disappear naturally by the time of puberty. Nevertheless, such problems may contribute to infections among those in this age group.

Certain forms of birth control, in addition to the act of intercourse itself, may contribute to urinary infections. The term “honeymoon cystitis” is often applied, reflecting the bacteriuria often found following intercourse. The colonization of E. coli may be associated with the use of diaphragms or spermicides. The reasons for this connection are unclear, but both appear to represent an alteration in the normal flora of the periurethral area and vagina.

Clinical manifestations of urinary tract infections vary with age and are often nonspecific. The infiltration of leukocytes (white blood cells), resulting in inflammation, accounts for many of the symptoms. Among children, abdominal pain is often present, accompanied by fever and sometimes vomiting. Among adults,
cystitis and
urethritis are often accompanied by difficulty in urination (dysuria), including painful urination and frequent urination, particularly in women. A sensation of abdominal heaviness or lower back pain, in addition to low-grade fever, is often observed. The urine may be bloody or turbid, reflecting a mixture of microbial agents and white blood cells. Bacteriuria is detected by the collection of a sample of voided urine and inoculation of an appropriate culture dish; the presence of at least 100,000 colony-forming units per milliliter of sample constitutes “significant
bacteriuria.”

Infection of the urinary tract may also result from a variety of sexually transmitted organisms. Chlamydial infections are common in both males and females, and they represent one of the most commonly observed forms of sexually transmitted disease (STD).

Chlamydia trachomatis causes urethritis in both males and females; though many chlamydial infections are asymptomatic, they can lead to severe complications. Urethritis may also result from other microbial STDs, both viral and bacterial.

The use of catheters, particularly among hospitalized elderly persons, is a frequent cause of urinary infections. An estimated 40 percent of nosocomial (hospital-acquired) infections result from the use of catheters. Despite attempts to maintain sterility through the use of closed, sterile drainage systems, by two weeks after catheterization 50 percent of both men and women have developed a urinary tract infection, and with longer or permanent catheterizations, nearly all persons will develop some degree of infection. In most cases, these infections are inapparent, but such persons remain predisposed to cystitis or urethritis.

The urinary tract is also subject to other disorders, including cancer. The most common form of neoplasm of the urinary tract is
bladder cancer. Such cancers tend to be highly aggressive, often occur as multiple growths, and are difficult to cure once metastasis has begun. Approximately two-thirds of cases of bladder cancer are diagnosed in men, perhaps in part a reflection of risk factors. Exposure to both cigarette smoke and carcinogens, particularly those used in the petrochemical industry, has been linked to an increased incidence of bladder cancers. The symptoms of bladder cancer resemble those of urinary tract infections: dysuria, cystitis, and the frequent need to urinate. If the tumor is diagnosed early enough, electrosurgery or resection may be sufficient to remove the lesion. If the tumor has begun to infiltrate the bladder tissue, complete removal of the bladder may be necessary. Radiation and chemotherapy are also commonly used in the treatment of certain forms of urinary tract cancers.

In May 2013, the journal Science Translational Medicine published a report suggesting that repeat urinary tract infections may be caused by a strain of E. coli bacteria present in the stomach or bladder. According to a study, an adaptable strain of E. coli that can survive repeated treatment efforts may be the cause of recurrent infections.

Treatment and Therapy

Standard treatment for urinary tract infections consists of a regimen of antimicrobial drugs. Ideally, the
antibiotics of choice are secreted in the urine over a prolonged period, rather than achieving high concentrations in the blood serum. In this manner, the drug is directed at the infection itself, with minimal effect on the normal flora elsewhere in the body.

Depending on whether the infection is limited to the lower urinary tract (urethra or bladder) or has spread to the upper tract (ureters or kidneys), the period of regimen may last for several days or up to two weeks. Generally, infections of the upper urinary tract require more prolonged treatment and may be subject to recurrence.

Standard therapy of conventional lower-tract infections routinely consists of a three-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX), or TMP alone. Since most of the drug combination is excreted in the urine, there is a minimum of side effects and little danger to the normal flora within the body. The short duration of treatment also minimizes the chances of encouraging the growth of resistant populations of bacteria. Elderly patients or persons with diabetes mellitus may require longer treatment. If the person shows evidence of upper-tract infection, treatment is generally given over a two-week period.

If there is evidence of kidney involvement or inflammation (pyelonephritis), the patient is often hospitalized in order to monitor treatment, which usually involves a fourteen-day course of TMP-SMX. Severe illness or evidence of spreading may require more intensive therapy with other antibiotics.

Since the flushing action of urine is itself a nonspecific means of removing bacteria from the bladder or urethra, patients are usually advised to drink as much water as possible. In this manner, weakly adherent or nonadherent bacteria may be flushed from the site of infection, reducing the number of bacteria and supplementing the course of antimicrobial therapy. In some cases, this action is sufficient to relieve symptoms or even cure the infection.

In situations in which the infection is asymptomatic, unless the situation warrants treatment (such as impending surgery), antimicrobial therapy may not be necessary, as the infection is self-limiting. Given the large proportion of persons, particularly women, who develop bacteriuria, forgoing therapy may minimize the chances for the artificial selection of resistant strains. In individuals with heart disease, renal failure, or diabetes, however, such therapy may be necessary as a preventive measure for later problems.

Bacteriuria during pregnancy represents a special situation. During early pregnancy, from 4 to 7 percent of women develop bacteriuria, which is probably related to such physiological changes as the dilation of the bladder and uterus, along with vesicoureteral (bladder and urethra) reflux. Even though the infection may be asymptomatic, urinary tract infection is associated with increased risk of both
pyelonephritis and loss of the fetus; about one-third of women with untreated bacteriuria during pregnancy develop infections within the upper urinary tract by the third trimester. For this reason, it is generally recommended that pregnant women be screened for such infections and undergo treatment if bacteriuria is present. Pregnant women generally undergo a three-day treatment regimen, though with alternative antibiotics considered safer in the presence of a developing fetus: ampicillin,
nitrofurantoin, or cephalexin. Patients should be monitored at intervals during the pregnancy to prevent recurrence. If pyelonephritis should develop, the woman is routinely hospitalized to allow close monitoring of both the mother and the fetus during therapy.

Bacteriuria associated with catheterization is generally treated only when it is symptomatic, since recurrence of the infection is common; long-term treatment presents no advantage and may select for antibiotic-resistant strains. Since the catheter may harbor bacteria, it usually is removed at the start of therapy.

The treatment of sexually transmitted diseases follows much the same pattern. Fortunately, most STDs can be treated or controlled. Both chlamydial infections and gonorrhea are generally treated with doxycycline, a derivative of tetracycline.

Perspective and Prospects

Urinary tract infections are notoriously difficult to prevent. Because in most cases the associated etiological agents are the normal intestinal flora, vaccination or prophylactic use of antibiotics would be impractical. Proper hygiene appears to be the most effective means of prevention among young adults.

STDs can be a source of urinary tract disease. Either a decrease in sexual promiscuity or more effective use of physical barriers (such as condoms) is necessary to reduce the level of such forms of infection. While vaccines against some of the more prevalent forms of STD (gonorrhea, chlamydia) remain a possibility, antibiotic therapy continues to be the most reliable means to treat urinary infections within the individual.

Catheters represent an important source of infection among the elderly, particularly those who are hospitalized. Since a single catheterization results in infection among less than 1 percent of patients, limiting catheterization, or avoiding it entirely, would appear to be the most effective preventive measure. The use of closed drainage systems has also reduced significantly the incidence of such infections. Antiseptic solutions and ointments have had limited success in the prevention of urinary tract infections. The use of antibiotic therapy has been effective in the short term, but over time such therapy may simply select for resistant mutants among the microorganisms. Development of catheters that do not lend themselves to microbial colonization, or that actively inhibit microbial growth (such as silver-impregnated catheters), may reduce the chances of such types of urinary tract infections.

Bibliography

Ammer, Christine. The New A to Z of Women’s Health: A Concise Encyclopedia. 6th ed. New York: Checkmark Books, 2009.

Boston Women’s Health Collective. Our Bodies, Ourselves: A New Edition for a New Era. 35th anniversary ed. New York: Simon & Schuster, 2005.

Gorbach, Sherwood L., John G. Bartlett, and Neil R. Blacklow, eds. Infectious Diseases. 3d ed. Philadelphia: W. B. Saunders, 2004.

Hooton, T.M. "Uncomplicated Urinary Tract Infection." New England Journal of Medicine. 366. (2012): 1028-1037.

Humes, H. David, et al., eds. Kelley’s Textbook of Internal Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Urinary Tract Infection. San Diego, Calif.: Icon Health, 2002.

Schrier, Robert W., ed. Diseases of the Kidney and Urinary Tract. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2007.

Stamm, W. E., and T. M. Hooton. “Current Concepts: Management of Urinary Tract Infections in Adults.” New England Journal of Medicine 329. (1993): 1328-1334.