The urinary bladder acts as a reservoir for urine, with function dependent on the internal muscular sphincter at the bladder neck. Bladder filling results in a sensory input that leads to socially acceptable voluntary urination. Normal bladder emptying requires higher impulses from the brain, spinal cord, and pelvic autonomic nerves. Muscular contraction of the wall with relaxation of the internal sphincter causes complete evacuation. Interference with innervation of the bladder—as in spina bifida, spinal cord neoplasms, spinal trauma (paraplegia), or multiple sclerosis—leads to various forms of bladder dysfunction, resulting in urinary incontinence, infection, stone formation, and hydronephrosis.
The bladder, like the renal pelvis, ureters, and urethra, is lined by urothelium, which is a stratified transitional epithelium up to seven layers of cells in thickness.
Anatomic abnormalities such as duplication—complete or incomplete—and congenital fistulas caused by abnormal development of the cloaca and urogenital sinus are rare.
The urachus is the canal that connects the fetal bladder with the allantois. After delivery, it becomes obliterated or remains as a fibrous cord, the median umbilical ligament. Persistence of the entire urachus causes a vesicoumbilical fistula; persistence of parts of the urachus predisposes to infection, sinuses, and fistula formation. Urachal cysts and neoplasms occur rarely.
Exstrophy of the Bladder (Ectopia Vesicae)
Exstrophy of the bladder is a rare congenital anomaly associated with failure of development of the anterior wall of the bladder and the overlying abdominal wall, including the pubic symphysis. The bladder is open to the skin surface as a large defect (complete exstrophy). Lesser defects also occur.
The exposed bladder is red and granular at birth and is covered by transitional epithelium. Repeated infections cause glandular metaplasia of the squamous or intestinal type. Isolated defects can be corrected surgically. Exstrophy is often associated with numerous other congenital anomalies.
A higher incidence of cancer (usually adenocarcinoma) is reported in exstrophic bladders.
Acute bacterial cystitis is a common ascending infection caused by coliform bacteria, commonly Escherichia coli, Proteus species, and Enterococcus faecalis. It occurs more commonly in females and is etiologically related to sexual intercourse, pregnancy, and instrumentation (Figure 50-4). In older individuals, chronic retention of urine in patients with prostatic hyperplasia is the major predisposing factor. The etiologic agent can be cultured from urine, which also contains protein, red cells, and neutrophils (casts are present only if the kidney is also involved). Many cases of acute cystitis are associated with acute pyelonephritis.
Causes and predisposing factors of bladder infections. Most cases are due to ascending infections caused by enteric bacteria such as E coli and Proteus species.
Radiation cystitis occurs in cases where the bladder is included in the field of pelvic irradiation for malignant neoplasms.
Drugs used in the treatment of cancer (eg, cyclophosphamide) cause acute hemorrhagic cystitis with marked atypia of the lining transitional epithelium that may be mistaken for cancer on cytologic examination of urine.
Acute cystitis is characterized by hyperemia of the mucosa with neutrophilic infiltration of the lamina propria. The term encrusted cystitis is used for nonspecific cystitis in which alkalinity of the urine causes precipitation of crystalline phosphates on the bladder mucosa; phosphate precipitation occurs in infections by organisms such as Proteus that split urea to form ammonia. Bullous cystitis is a variant of acute cystitis in which large fluid-filled spaces form in the lamina propria.
Acute cystitis is characterized by fever, low abdominal pain, frequency of micturition, and dysuria. Frequency is the result of trigonal irritation, which stimulates the sensory arc of the micturition reflex.
Diagnosis is established by quantitative culture (colony count) of a midstream urine specimen. Specific treatment depends on the results of culture and sensitivity tests. While waiting for culture results, treatment should be started with an antibiotic effective against the common agents (eg, ampicillin, trimethoprim-sulfamethoxazole). The prognosis is excellent.
Vesical tuberculosis occurs in 70% of patients with renal tuberculosis and is a common presenting symptom in patients with urinary tract tuberculosis. The ureters and epididymis may also be involved.
The trigone is affected first, with the early lesions appearing as small submucosal granulomas. Extensive caseous granulomas may cause nodules and ulceration, while the associated fibrosis may cause retraction of the ureteral orifice into the wall of the bladder (“golf-hole ureter”) with vesicoureteral reflux. Diffuse involvement of the bladder is associated with marked fibrous contraction of the bladder (“thimble bladder”). At this stage, urinary frequency is extremely severe.
Clinically, there is frequency, pain, dysuria, and pyuria. Low-grade fever and weight loss may be present. Cultures for mycobacteria are diagnostic.
The perivesical venous plexus is the favored habitat of Schistosoma haematobium, a species that is common in Egypt and the Middle East. The ova pass through the bladder wall to enter the lumen and are excreted in urine. Finding typical ova in the urine is diagnostic.
In their passage through the wall, the ova cause marked inflammation, with abscesses and granulomas in which there are large numbers of eosinophils. Vesical schistosomiasis is associated clinically with fever, frequency, dysuria, and hematuria. Cystoscopic examination shows scarring and small nodules in the bladder mucosa. Marked fibrosis occurs in the chronic stage.
The bladder epithelium frequently shows squamous metaplasia. There is a greatly increased risk of squamous carcinoma.
Chronic Nonspecific Cystitis
Chronic nonspecific cystitis is characterized by epithelial hyperplasia and infiltration of the bladder mucosa with lymphocytes and plasma cells. Cystic dilation of epithelial nests in the submucosa (Brunn's nests) may produce multiple epithelium-lined cysts in the mucosa (cystitis cystica). Glandular metaplasia may occur (cystitis glandularis). These forms of epithelial change have little clinical significance. The cause is not known. One form of chronic nonspecific cystitis characterized by ulceration of the mucosa with submucosal fibrosis, vasculitis, and infiltration by eosinophils is called Hunner's interstitial cystitis.
A histologically distinct type of chronic inflammation occurs in patients with chronic bladder dysfunction and trauma, especially those with neurologic disease. This is characterized by a peculiar metaplasia of the urothelium called nephrogenic metaplasia. In some cases, this metaplastic epithelium becomes polypoid (nephrogenic “adenoma”).
Malacoplakia is a peculiar chronic inflammation characterized by yellowish plaques, nodules, or polyps in the bladder mucosa. The lesions are composed microscopically of dense collections of macrophages with abundant granular cytoplasm. Within the cytoplasm are round, laminated concretions—called Michaelis-Gutman bodies—that stain positively with periodic acid-schiff (PAS) (periodic acid-Schiff stain) as well as calcium and iron stains. The macrophages also contain partially digested bacterial remnants, leading to the hypothesis that malacoplakia is caused by defective removal of phagocytosed bacteria by macrophages.
Malacoplakia is most commonly found in the bladder; other sites include the renal pelvis, ureter, prostate, epididymis, colon, and lungs.
Bladder diverticula may be congenital or acquired and may occur in childhood or in the elderly. Most acquired diverticula result from bladder neck obstruction, the most common cause of which is prostatic hyperplasia. Bladder neck obstruction results in muscular hypertrophy and increased intraluminal pressure leading to “pulsion” diverticula.
The most common location of diverticula is near the ureteral orifice. The presence of a bladder diverticulum results in stasis of urine and susceptibility to infection and formation of bladder calculi. There is also an increased incidence of urothelial neoplasms in diverticula, probably due to increased contact time between the mucosa and urinary carcinogens.
Bladder fistulas may communicate with the skin, intestine, or female reproductive organs. Such fistulas may be (1) congenital, eg, urachal vesicoumbilical fistula or, rarely, vesicovaginal fistula; (2) traumatic—mainly obstetric trauma, which may be complicated by vesicovaginal fistula; (3) inflammatory, as in diverticulitis of the colon, salpingitis, and Crohn's disease—diverticulitis is the most common cause of vesicointestinal fistula; or (4) neoplastic, particularly carcinoma of the cervix, colon, and bladder.
The clinical effects of bladder fistulas depend on the organs involved. Vesicovaginal fistula produces constant dribbling of urine through the vagina. Vesicointestinal fistula causes passage of feces (fecaluria) and gas (pneumaturia) with urine. All fistulas predispose to vesical infection.
Calculi may form in the bladder (primary) or descend from the kidney (secondary). They have the same composition and causes as renal calculi.
Amyloidosis of the Bladder
Amyloidosis is rarely localized in the bladder and presents as hematuria. Amyloid deposition may appear as a mucosal plaque or nodule or may involve the bladder more diffusely, causing irregular thickening of the mucosa and wall. Hemorrhage caused by rupture of amyloid-affected vessels is common.
Bladder cancer is fairly common, and it is responsible for about 3% of cancer deaths in the United States and Europe. The incidence is 40,000 per year in the United States and the death rate is 10,000 per year. The disease has a marked geographic variation. In Japan, the incidence is extremely low, while in Egypt it accounts for 40% of cancers (because of the high incidence of schistosomiasis).
Bladder cancer has been related to several chemical carcinogens such as aniline dyes containing benzidine and 2α-naphthylamine, which were responsible for bladder cancer in workers in the dye, rubber, and insulating cable industries. The latent period may be many years.
Probably the most important etiologic factor in the genesis of human bladder cancer in the United States is cigarette smoking. Smoking increases the risk to two to four times that of nonsmokers. The mechanism by which smoking causes bladder cancer is unknown. In Egypt, schistosomiasis is important, producing squamous metaplasia, dysplasia, and squamous carcinoma.
Abnormalities in chromosomes 9 and 17 have been reported in the cells of urothelial neoplasms.
Overt Urothelial Neoplasms
Urothelial neoplasms may occur anywhere in the bladder mucosa. The most common locations are near the trigone or in a diverticulum. Large tumors may involve a large area of the mucosal surface and cause obstruction of the ureteral orifices (Figure 50-5).
Bladder carcinoma, showing a large neoplasm almost filling the lower half of the bladder.
The better-differentiated urothelial neoplasms commonly project into the lumen and have a delicate papillary appearance. In contrast, poorly differentiated neoplasms are solid ulcerative lesions that frequently show evidence of infiltration of the bladder wall.
Microscopically, over 90% are transitional cell carcinomas. Squamous or glandular differentiation commonly occurs in transitional cell carcinomas.
The international (World Health Organization) histologic grading system for urothelial neoplasms recognizes four histologic grades.
Transitional cell papilloma is a well-differentiated noninvasive papillary neoplasm that has seven or fewer layers of cytologically normal transitional cells lining the papillary fronds. This tumor is rare and benign but tends to be multifocal, often recurring after surgery.
Grade I transitional cell carcinoma shows well-formed papillary structures lined by an epithelium that is cytologically normal but thicker than seven layers. Invasion is uncommon.
Grade II transitional cell carcinoma has papillary and solid areas. The cells show mild to moderate cytologic atypia and have a greater degree of pleomorphism (Figure 50-6). Invasion may occur.
Grade III transitional cell carcinoma has a predominantly solid invasive growth pattern with or without a papillary structure and shows cytologic anaplasia and a high rate of mitotic figures. It may be difficult to recognize its transitional cell nature. Some authorities recognize a grade IV carcinoma, which represents a more anaplastic variant of grade III with evidence of cell necrosis.
Transitional cell carcinoma of the bladder, showing papillary fronds lined by atypical transitional epithelium.
The critical distinction in terms of behavior and treatment is between grade I or II (well-differentiated) and grade III (poorly differentiated) carcinomas. Grade III carcinomas are frequently associated with carcinoma in situ of the adjacent mucosa (see below).
Infiltration of the tumor must be assessed independently of histologic grade. Infiltration of lamina propria, muscle wall, or blood vessels has adverse prognostic significance.
Dysplasia and Carcinoma in Situ
In high-grade bladder carcinomas, the urothelium is believed to progress through dysplasia to carcinoma in situ before it invades the basement membrane. Carcinoma in situ usually occurs in men over 40 years of age and causes no symptoms or gross changes in the bladder mucosa. Random bladder biopsy or cytologic examination of urine is necessary for diagnosis. Microscopically, the epithelium shows disturbed maturation and cytologic abnormalities such as an increased nuclear:cytoplasmic ratio, disturbed chromatin pattern, and hyperchromasia. Cytologic examination of urine shows malignant transitional cells.
Carcinoma in situ is frequently multifocal and may extend into the urethra and ureters. The prognosis is bad, with many patients developing high-grade invasive carcinoma.
Painless hematuria is the most common presenting symptom of bladder carcinoma. Involvement of the trigone may cause frequency and dysuria. Involvement of the ureteral orifice may lead to hydronephrosis and infection. Rarely, invasion of adjacent organs (colon, vagina) (Figure 50-7) leads to fistulous tracts. Dysplasia and carcinoma in situ are asymptomatic.
Mode of dissemination of urothelial neoplasms of the bladder. The percentages refer to the distribution of cancers in different parts of the bladder.
The diagnosis is made by cystoscopy and biopsy.
Clinical staging depends on the degree of invasion by the neoplasm and the presence of lymph node and distant metastases (Table 50-2).
Staging of Transitional Cell Carcinoma of the Bladder.
Staging of Transitional Cell Carcinoma of the Bladder.
Carcinoma in situ
Papillary neoplasm without invasion
Invasion of lamina propria
Invasion of superficial half of the muscle wall
Invasion of deep half of the muscle wall
Invasion through bladder wall into perivesical fat
Invasion of prostate, vagina, or uterus
Tumor fixed to pelvic or abdominal wall
Pelvic nodes involved
Involvement of lymph nodes above the aortic bifurcation
The mainstay of treatment of bladder cancer is surgery. Radical cystectomy is indicated for poorly differentiated carcinomas and well-differentiated carcinomas in which there is muscle invasion. Local resection or partial cystectomy suffices for better-differentiated noninvasive neoplasms. Immunotherapy with intravesical bacillus calmette-guérin (BCG) has proved effective for dysplasia and carcinoma in situ.
The prognosis depends both on clinical stage and histologic grade. With appropriate surgical resection, 50–80% of patients with stage II neoplasms survive 5 years. With local extension outside the bladder, the 5-year survival rate drops to 20–30%. The better differentiated the neoplasm (lower grade), the better the prognosis.
Other Epithelial Neoplasms
Pure squamous carcinoma is rare except where schistosomiasis is endemic, in which case it represents the most common type.
Well-differentiated keratinizing squamous carcinoma tends to form large, bulky exophytic masses that protrude into the lumen. They tend to remain confined to the bladder until a late stage and have a better prognosis than transitional carcinomas of similar size.
Pure Adenocarcinoma of the Bladder
Adenocarcinoma is rare but may arise (1) in urachal epithelial remnants in the dome of the bladder; (2) in bladder mucosa that has undergone glandular metaplasia; and (3) in cystitis glandularis.
Paragangliomas of the urinary bladder are rare and originate in paraganglionic structures in the bladder wall. They resemble pheochromocytomas of the adrenal gland. Most are nonfunctional. Functional paragangliomas secrete bursts of catecholamines during urination, causing palpitations and hypertension.
Mesenchymal neoplasms are rare. Smooth muscle tumors (leiomyoma and leiomyosarcoma) are the most common of these; embryonal rhabdomyosarcoma occurs in young children.