Introduction

The urinary system consists of the kidneys, ureters, urinary bladder, and urethra (Figure 15.1). The kidneys are the central organ of the system and are responsible for filtering wastes from the blood as well as for removing any excess liquid, thus forming urine. The functional units in the kidneys are the nephrons (Figure 15.2) and in addition to their filtering capacity they also keep a stable balance of minerals, salts, and other substances to maintain the homeostasis (the maintenance of a relatively stable environment of the body) of the blood. Furthermore, the kidneys produce erythropoietin, the hormone that aids in the formation of red blood cells. The ureters are narrow tubes that carry the urine from the kidneys to the urinary bladder, which stores the urine for later expulsion from the body. The urine stored in the urinary bladder is emptied through the urethra, whose length varies between male and female. The male urethra is longer than the female and the opening is located on the penis. Normally urine is sterile, free of any microorganisms; however, an infection can occur when infectious organisms, usually bacteria from the gastrointestinal tract, gain access to the opening of the urethra and multiply. The urinary tract is one of the most common sites of bacterial infection, particularly in females.

Urinary Tract Infections (UTIs)

There are a number of organisms that can be responsible for a urinary tract infection (UTI) infection but the most common is Escherichia coli, a gram-negative, facultatively anaerobic rod that can thrive in a relatively wide range of pH. The infection may remain localized in the urethra, but the organisms can also travel up the urethra and infect the urinary bladder. When a urinary bladder infection is not treated, it may spread to the kidneys. In a small number of cases, UTIs have been caused by organisms that originated in oral/gum infections. In these cases the organisms traveled through the bloodstream to the kidneys, where they gave rise to a kidney infection. In healthy individuals the urinary system is designed to prevent urine from backing up from the urinary bladder to the ureters and kidneys, and the flow of urine from the bladder typically helps wash away any microorganisms. The prostate gland in men also produces slightly acidic secretions that tend to slow bacterial growth. These structural and chemical mechanisms, along with the actions of a healthy immune system, are normally effective at preventing UTIs. The type of infection is typically defined by the organ or structure where the infection is located.

Organisms that cause UTIs may be sexually transmitted and the infections usually remain limited to the urethra and the organs of the reproductive system. Not all individuals with a UTI show easily recognizable symptoms, but most cases include the following:

• Urgency to urinate

• Burning/painful sensation when urinating (dysuria)

• Frequency of urination, passing only small amounts each time

• Presence of blood or pus in the urine, or a cloudy, strong-smelling urine

Other symptoms may vary among individuals and depend on the specific type of infection. These symptoms may include the following:

• Uncomfortable pressure above the pubic bone in women

• A fullness of the rectum in men

• Pain in the back or side below the ribs

• Nausea

• Vomiting

• Fever

• Irritability

• Loss of appetite in children

Urinary tract infections are identified by the specific location or organ being affected by the microorganisms. The most common infections are urethritis, cystitis, pyelonephritis, leptospirosis, and glomerulonephritis.

Urethritis

Urethritis is a localized infection usually limited to the urethra. It can be caused by E. coli but also by Chlamydia or Mycoplasma, because the urethra is also associated with organs of the reproductive system. A common source of this infection for older or hospitalized patients is a catheter. If not treated early, the infection can travel up the catheter and spread the infection to the urinary bladder. Trichomonas vaginalis, a protozoan, has also been associated with urethritis as well as vaginitis (see Chapter 16, Infections of the Reproductive System). Enterococci and Candida albicans are other organisms that occasionally can cause urethritis.

Cystitis

Cystitis is an infection that occurs in the urinary bladder and is sometimes simply referred to as a bladder infection. E. coli is the primary cause of this infection but others, such as Staphylococcus species, and members of Proteus, Enterobacter, Klebsiella, and Candida, have also been identified as organisms causing urinary bladder infections. The bacteria travel up the urethra, sometimes via a catheter, into the bladder, where they multiply and cause inflammation. If the infection remains untreated, it can spread to the kidneys, causing an even more serious infection. The helminth Schistosoma haematobium has been associated with urinary bladder infections and the human polyomaviruses JC and BK can cause hemorrhagic cystitis.

Pyelonephritis

Pyelonephritis is often referred to simply as a kidney infection, and this serious infection can cause extensive and permanent damage to the kidneys. The same organisms responsible for most cases of cystitis are also responsible for most kidney infections, with E. coli alone being responsible for more than 80% of these infections.

Leptospirosis

The spirochete Leptospira interrogans is a zoonotic organism that can cause a kidney infection or other nonspecific illnesses. Many mammals such as dogs, cats, and rats carry the organism, which can come in contact with humans through contaminated urine, direct contact with the animal, or through water or soil. Many cases of leptospirosis are asymptomatic and fewer than 100 cases are reported each year in the United States.

Glomerulonephritis

Glomerulonephritis, also referred to as Bright’s disease, involves inflammation and damage to the glomeruli of the kidneys. This is actually an immune complex disease that sometimes follows an oral streptococcal or viral infection. Antibody–antigen complexes are eventually filtered out in the kidneys, where they cause inflammation. This infection can cause some permanent damage to the kidneys and can be fatal.

Diagnosis of UTIs

Typically the detection/diagnosis process occurs in two stages. The first stage involves gathering a sample of urine for evaluation and the second stage involves testing the antibiotic sensitivity of any microorganisms that may be present. The collection of urine involves a procedure called a “clean catch,” wherein the patient thoroughly washes the genital area and then collects a midstream sample in a sterile container. The sample can then be both cultured for microbial growth as well as examined microscopically to determine the presence of microbes, pus, or blood. Typically the urine sample is streaked on a blood agar plate, using a special pattern to provide a semiquantitative analysis of the sample (Figure 15.3). If microbial growth occurs on the growth medium, the organisms can be tested with various antibiotics to identify the most effective one against a specific pathogen. This step is called a sensitivity test. The general term for the presence of bacteria in the urine is bacteriuria.

Risk Factors for UTIs

The risk factors for UTIs vary from individual to individual and from situation to situation; however, there appear to be certain factors that are common in many patients. The following groups exhibit unique risk factors:

• Diabetics: Patients with diabetes often have a higher risk for UTIs because of changes in the immune system that make them more vulnerable to infection.

• Patients with catheters: Patients with catheters in place for extended periods of time have an increased risk of infection of the urethra and ultimately the urinary bladder. About 20% of patients catheterized for more than 30 days will develop UTIs. The catheter itself can act as a location for the development of a biofilm (see Chapter 3, Cell Structure and Function), resulting in a greater diversity of species than may normally be found in the urinary bladder.

• Infants/children with abnormalities of the urinary tract: In boys the infections usually occur before the first birthday, and in girls the infections are common around the age of 3 years, overlapping with the period of toilet training. Infections in girls at a young age are especially dangerous because chronic infections over a long time period can lead to serious kidney damage. Some abnormalities that may lead to UTIs in children include vesicoureteral reflux (VUR), urinary obstruction, and dysfunctional voiding. VUR involves the reverse flow of urine from the bladder up the ureters and back to the kidneys. This condition can be corrected by surgical repositioning of the connection between the ureters and the urinary bladder in order to prevent the reverse flow. Urinary obstructions can include narrow ureters, kidney stones, or improper connection of the ureters to the kidneys or urinary bladder. Obstructions are typically solved by corrective surgical procedures or dissolving of the stones. Dysfunctional voiding is often a behavioral problem wherein children may intentionally delay voiding the bladder. This problem involves a simple process of behavior modification.

• Women: The largest group of patients who suffer with UTIs are adult women. Anatomically, women have a higher risk of infection because of the short length of the urethra and the close proximity of the opening to the anus (Figure 15.4), thus presenting a higher risk of fecal bacteria entering the urethra. Statistics also indicate that the incidence of infection increases with age and sexual activity. Rates of infection are particularly high in postmenopausal women because of incomplete urinary bladder emptying, and the loss of estrogen, which results in changes in the vaginal flora. Furthermore, the loss of normal flora such as lactobacilli decreases the level of competition with organisms such as E. coli. In addition, the tissues of the urethra become thinner and more fragile due to a decrease in estrogen, providing a good environment for opportunistic organisms. Sexual activity can irritate the urethra, allowing bacteria to more easily penetrate and move to the urinary bladder. The regular use of a diaphragm as a contraceptive measure can also lead to increased risk of infection particularly in premenopausal women.

• Men: The occurrence of UTIs in men under the age of 50 years is relatively low. The infections that do occur in this group are largely due to sexual activity that causes irritation of the urethra and subsequent penetration of the bacteria into the urinary bladder (Figure 15.5). There is evidence that uncircumcised men are at higher risk of developing a UTI. Most cases that occur in older men are associated with an obstruction or a medical procedure involving the placement of a catheter. In most cases an obstruction may be the result of kidney stones, blood clots, tumors, scar tissue, or a structural defect such as kinking of the ureters or a compression of the ureters by fibrous connective tissue. Surgical procedures can correct most of these defects. In the case of kidney stones, sound shock waves are commonly used if the stones do not pass through the system naturally; surgery is generally not the first course of treatment. Those older men who have an infection of the prostate gland are also at higher risk for a UTI.

LIFE APPLICATION

Circumcision

It has been shown that circumcision in the first year of an infant’s life will provide significant protection against UTIs, and even in adults circumcision shows protection against UTIs. Infections of the urinary tract in infants can lead to significant morbidity in boys prior to 6 months of age. Complications of UTIs in infants include kidney infections and generally abnormal kidney function that in the future may cause high blood pressure and kidney failure. The lack of circumcision has been shown to be a risk factor for urinary tract infections in newborn boys.

Prevention and Treatment of UTIs

Prevention of UTIs

Specific prevention measures depend on the individuals involved, and the risk factors vary between groups on the basis of sex and age. The preventive measures are outlined according to the groups previously identified.

• Diabetics: Preventive measures generally involve actions that improve the health of a diabetic, such as careful control of glucose levels and blood pressure. Those measures will ensure a healthy immune system that in turn will help to prevent UTIs.

• Patients with catheters: The best measures to prevent a UTI are frequent cleaning of the catheter and associated areas, and its removal, done as soon as it is no longer necessary. Although there is some debate about when a transurethral catheter should be changed, the practice in most health facilities is to do a monthly change. On diagnosis of a UTI, catheters need to be changed immediately. Because of the potential for UTIs and other complications, federal regulations mandate that indwelling catheters should be used only when there is valid medical justification.

• Infants/children with abnormalities of the urinary tract: The most effective measure is early identification of the problem followed by corrective surgery or procedures done as soon as possible.

• Women: The following measures have been suggested to help prevent infections in women:

• Don’t resist the urge to urinate.

• Wipe from front to back to prevent bacteria around the anus from being spread to the area of the urethra.

• Take showers instead of tub baths.

• Cleanse the genital area before sexual intercourse.

• Urinate after intercourse.

• Avoid using feminine hygiene products, which may irritate the urethra.

• Drink plenty of water every day.

• Men: Basic measures for men include the following:

• Drink plenty of water every day.

• Cleanse the genital area before intercourse.

• Don’t resist the urge to urinate; urinate when you feel the need.

• Urinate after intercourse.

MEDICAL HIGHLIGHTS

UTI Prevention: The Promise of New Vaccines

Statistically, UTIs are becoming almost as common as the common cold. E. coli continues to be the bacterium primarily responsible for most UTIs and although the majority of these infections are not life-threatening, they result in more than 7 million visits to the doctor annually. Recent research in vaccines to prevent UTIs has been showing promise on a number of fronts. One of the areas involves preventing the physical attachment of E. coli to the surface of the epithelium that lines the regions of the urinary tract. Without the attachment to tissue, bacteria are not able to colonize and cause infection. The vaccines being developed target the pili protruding from the surface of E. coli; the pili are the structures responsible for attachment. Other areas of research are also investigating the use of vaccines to enhance the effectiveness of dendritic cells—part of the body’s immune system—to more effectively identify and destroy E. coli within the urinary tract. At this time most of these vaccines are in the clinical testing stage of development, but it does not appear that it will be too long before they should be readily available to the general public.

Treatment of UTIs

Once the causative pathogen has been identified, the treatment regimen with specific antibiotics may be determined. Determination of the specific drug to be used and the length of treatment depends on the pathogen involved. The general health of the patient is also a major component of the treatment. For example, specific treatment may be based on the category to which the patient belongs: diabetic, pediatric, hospitalized/nonhospitalized, male, or female (further subdivided into pregnant and nonpregnant). The following is a list of drugs commonly used for simple UTIs:

• Amoxicillin

• Nitrofurantoin

• Trimethoprim

• Combination of trimethoprim and sulfamethoxazole

• Gentamicin

• Ciprofloxacin

• Cefadroxil

• Mecillinam

• Fosfomycin

• Cephalosporins

With effective treatment UTI symptoms will clear up within a few days. However, antibiotics may need to be continued for a week or so to prevent recurrence. As with all antibiotics it is important that a patient take the entire course of medication that was recommended to ensure that the infection is completely eliminated and to avoid development of antimicrobial resistance. Recurrent UTIs will require a longer course of antibiotic treatment. In infections caused by sexual activity, such as Chlamydia or Mycoplasma infections, a single dose of antibiotic may be recommended after sexual intercourse. Severe UTIs may require hospitalization and intravenous administration of antibiotics.

HEALTHCARE APPLICATION
UTI Antibiotics

Antibiotic	Trade Name	Comments
Amoxicillin	Amoxil, Augmentin, Apo-Amoxi	β-Lactam antibiotic, effective against gram-positive bacteria
Cephalosporins	Keflex, Ultracef, Duricef, Velosef, Ceclor, Cefzil, Ceftin, Lorabid, Vantin, Omnicef, Spectracef, Suprax, Cedax, Rocephin	Used in treating resistant infections
Trimethoprim-sulfamethoxazole (TMP-SMX)	Bactrim, Cotrim, Septra	Serious allergic reactions are possible; high rate of resistance in some parts of the United States
Fluoroquinolones	Floxacin, Cipro, Noroxin, Levaquin, Tequin, Zagam	Wide spectrum, expensive, dangerous side effects in pregnant women and children
Nitrofurantoin	Furadantin, Macrodantin, Macrobid	Specifically used for UTIs; not useful for kidney infections; can upset stomach; reacts with other drugs; not to be given to mothers near end of pregnancy, nursing, or with kidney disease
Fosfomycin	Monurol	Resistant rates are low; safe for pregnant women
Tetracyclines
Tetracycline Doxycycline Minocycline

Achromycin, Tetracyn, Tetramed, Cyclopar, Tetracycline, Sumycin
Doxycycline, Doxycin
Periostat, Arestin, Minocin, Dynacin Effective against UTIs caused by Mycoplasma and Chlamydia; side effects include skin reactions to sunlight Aminoglycosides    

Gentamicin

Kanamycin

Tobramycin

Amikacin

Gentamicin, Alcomicin, Garamycin, Gentacidin
Kantrex
Tobramycin, Nebrin
Amikin Given only in combination with other antibiotics; serious side effects may include: damage to hearing, sense of balance, and kidney damage Ertapenem Invanz Possible seizures and adverse CNS reactions

Bacterial Infections

Most UTIs are caused by bacteria and the primary microorganism responsible for most UTIs is E. coli; however, Chlamydia, a gram-negative, coccoid obligate parasite, and Mycoplasma, a gram-negative, pleomorphic facultative anaerobe, may also cause infections. Some other organisms that have been associated with UTIs are Klebsiella, Proteus, Enterobacter, Citrobacter, Serratia, Pseudomonas, Enterococcus, and coagulase-negative Staphylococcus. The actual designation as a bacterial UTI is based on the presence of greater than 100,000 colony-forming units (CFU)/1 ml of urine. A summary of the most common bacterial infection of the urinary system is shown in Table 15.1.

In some cases, especially in older adults, bacteria may be present in the urine without any indication of infection. This condition is known as asymptomatic bacteremia and usually does not require treatment. There has been some research into the possible connection between UTIs in older adults and delirium or dementia. At this time there does not appear to be a consensus in the medical community as to whether a UTI causes diminished mental capabilities or if the UTI is the result for a patient who is exhibiting mental difficulties and not voiding his or her urine regularly.

Viral Infections

Viral UTIs are rare, but certain viruses may be found in urine even in the absence of urinary tract infections/disease. These viruses include human polyomaviruses JC and BK, cytomegalovirus (CMV), adenovirus, hantavirus, and a number of other viruses that can infect the kidneys, including mumps and HIV. Viruses are increasingly recognized as the cause of lower UTIs, especially hemorrhagic cystitis after stem cell and organ transplantation. Early diagnosis and treatment of viral UTIs may prevent the significant morbidity of hemorrhagic cystitis. Diagnosis of viral UTIs is based on molecular techniques including the polymerase chain reaction (see Chapter 25, Biotechnology), which allows quantification of the viral load. The current drug of choice against viral UTIs is cidofovir, because it is active against the most common viral pathogens.

Polyomaviruses JC and BK

Polyomaviruses JC and BK enter the human body via the respiratory route, spread throughout the body, and infect the epithelial cells of the kidney tubules and ureters. The viruses then establish latency, with the viral genome being present but not infectious in healthy people. Approximately one third of healthy individuals show the DNA sequence of these polyomaviruses in their kidneys without experiencing symptoms. Reactivation of these viruses may occur during pregnancy and also in immunocompromised patients, resulting in large amounts of virus in the urine. In some transplant patients the BK virus manifests itself subsequent to the necessary use of immunosuppressant medication and ultimately attacks the kidney via BK nephropathy.

Ureteric stenosis in renal transplant patients has been associated with polyomavirus infections. The viruses induce proliferation of the transitional epithelial cells of the ureters, which can lead to partial obstructions or stricture formation. The BK virus also has been associated with cases of acute hemorrhagic cystitis following bone marrow transplantation.

Cytomegalovirus

Cytomegalovirus infections are widely recognized as potentially serious causes of complications in the lung, spinal fluid, and brain, and also as the cause of graft failure in renal transplantation. Cytomegalovirus can also cause asymptomatic shedding in the urine of congenitally infected infants (see Congenital Infections in Chapter 23, Human Age and Microorganisms).

Adenovirus

Adenoviruses are a group of viruses that typically cause respiratory illnesses (see Chapter 11, Infections of the Respiratory System), but can also cause infections of the urinary and intestinal tracts. Some serotypes of the adenovirus have been implicated as the cause of hemorrhagic cystitis. In immunocompromised patients severe adenoviral infections are serious complications, especially in patients receiving hematopoietic stem cell transplantations. The most critical and fatal for these transplant patients are adenovirus-induced urinary tract infections and acute necrotizing tubulointestinal nephritis.

Fungal Infections

Fungal infections of the urinary tract affect primarily the bladder and the kidneys, with Candida species being the most common cause. However, all invasive fungi such as Cryptococcus neoformans, Aspergillus species, Mucoraceae species, Histoplasma capsulatum, Blastomyces species, and Coccidioides immitis may infect the kidneys as a result of a systemic or disseminated mycotic infection. Candida infections are usually associated with a urinary catheter, often after bacteriuria and antibiotic therapy. Renal candidiasis spread by the blood commonly originates from the gastrointestinal tract. Other Candida infections can occur in patients with nephrostomy tubes, other permanent indwelling devices, and stents. At high risk for these infections are patients who are immunocompromised because of chemotherapy, AIDS, or immunosuppressants after transplantation. Fungal pathogens are a cause of the increasing numbers of healthcare-associated (nosocomial) infections (see Healthcare-associated [Nosocomial] Infections in Chapter 9, Infection and Disease).

Parasitic Infections

Few parasites cause UTIs in humans; they include the protozoan Trichomonas vaginalis and the helminth Schistosoma haematobium. Trichomonas vaginalis can cause urethritis in both males and females, but in females it often also causes vaginitis (see Chapter 16, Infections of the Reproductive System).

Schistosomiasis is one of the most common parasitic infestations in the world, caused by flukes in the genus Schistosoma (see Helminths in Chapter 8, Eukaryotic Microorganisms). The organism associated with urinary schistosomiasis is Schistosoma haematobium, found in the Middle East, India, Portugal, and Africa; to date it does not exist in the United States. Typically the infection involves the bladder, but ureteral involvement can be found in as many as 30% of the patients. Adult Schistosoma is present in the venous plexuses around the urinary bladder, where they release their eggs. The eggs then cross the wall of the bladder, causing hematuria and fibrosis of the bladder. Subsequently the bladder becomes calcified, which increases the pressure on the ureters and kidneys. The main cause of schistosomiasis is the contamination of water supplies with human waste.

Summary

Review Questions