Chapter 50. The Ureters, Urinary Bladder, & Urethra

(Figure 50-1)

Urinary obstruction is a common cause of renal dysfunction. It is important to recognize because many of its causes are treatable. The effects of obstruction depend mainly on whether one or both sides are affected. Urinary obstruction produces distention of the renal pelvicaliceal system that is called hydronephrosis.

Etiology

Unilateral Hydronephrosis

Obstruction of one side is commonly due to pathologic processes proximal to the urinary bladder (Figure 50-1). These result in hydronephrosis and may cause atrophy and loss of function of one kidney but do not cause renal failure. The causes include the following:

Ureteropelvic Junction Obstruction

This is a common disorder. While a few patients have an anatomic obstruction—most commonly an aberrant renal artery compressing the upper ureter—most cases are idiopathic (idiopathic hydronephrosis). In these patients, there is functional obstruction at the ureteropelvic junction with a patent lumen. Congenital abnormalities of the ureteropelvic musculature or innervation have been suggested as being the cause, and surgical removal of this region with reanastomosis results in cure. The obstruction is severe, and there is progressive dilation of the renal pelvis (hydronephrosis) above the ureteropelvic junction. The ureter is normal. The effects on the kidney vary. In patients with a renal pelvis that is extrarenal, massive dilation produces a huge cystic mass at the renal hilum that may present as an abdominal mass. In these cases the increase of pressure in the kidney is less than when the pelvis is intrarenal, and distention causes enlargement of the pelvicaliceal system, leading to renal atrophy (Figure 50-2).

Congenital Diseases of the Ureters

Other congenital anomalies of the ureters may cause unilateral hydronephrosis. These include double ureter, bifid ureter, and abnormalities in ureteral muscle causing increased wall thickness (megaureter). A ureterocele is a cystic dilation of the terminal part of the ureter caused by congenital stenosis of the ureteral orifice in the bladder wall. The cystic terminal ureter commonly protrudes into the bladder lumen. While these ureteral abnormalities may present in childhood, many of them are either found incidentally or produce symptoms in adult life.

Acquired Diseases of the Ureters

These are common and include (1) luminal obstruction due to calculi, blood clots, or sloughed necrotic renal papillae; (2) mural causes such as fibrous strictures and neoplasms; and (3) extrinsic compression of the ureters in retroperitoneal fibrosis and retroperitoneal neoplasms.

Fibrous strictures may follow inflammation, tuberculosis, or injuries to the ureter, which are most commonly caused by pelvic surgery for gynecologic cancers. Neoplastic lesions, both primary and metastatic, rarely involve the ureters primarily. More commonly, retroperitoneal and pelvic malignancies obstruct the ureter as they infiltrate. The ureter may also be obstructed in its terminal part as it passes through the bladder wall. Bladder cancer is commonly complicated by unilateral hydronephrosis.

Bilateral Hydronephrosis

1. Distal to the bladder, the most common cause is prostatic hyperplasia in older men, although congenital posterior urethral valves may cause bilateral hydronephrosis in young children. In paraplegic patients with neurogenic bladders, bilateral hydronephrosis is common.

2. Causes involving both ureters include retroperitoneal fibrosis or malignancies.

3. Ureteral muscle dysfunction occurring in pregnancy, probably due to the effect of progesterone on the smooth muscle, may also produce mild hydroureter and hydronephrosis.

Pathology

Acute complete obstruction of the ureter in experimental animals causes rapid dilation and increased luminal pressure proximal to the obstruction. Glomerular filtration continues, with increased filtration in the tubules and accumulation of fluid in the interstitium. Increased interstitial pressure leads to tubular dysfunction. Irreversible nephron loss occurs in about 3 weeks. With incomplete obstruction, irreversible damage takes much longer and depends on the degree of obstruction.

Most causes of urinary obstruction described above produce slow, incomplete obstruction to urinary flow. This results in hydronephrosis and progressive renal cortical atrophy due to nephron loss over many months or even years (Figure 50-2). Only bilateral hydronephrosis has the ability to cause renal failure. Stasis of urine associated with obstruction increases the incidence of acute pyelonephritis and the formation of urinary calculi, both of which can aggravate the obstruction.

Clinical Features

Acute ureteral obstruction by calculi, blood clot, or sloughed renal papillae causes ureteral colic due to increased peristalsis in the ureter. Ureteral colic is an intermittent, often excruciating pain in the posterior renal angle that radiates around the flank to the pubic region. Chronic unilateral obstruction is usually asymptomatic even when complete, and it commonly leads to permanent renal damage before it is detected. Chronic partial bilateral obstruction presents with features of progressive chronic renal failure, including hypertension, failure of tubular function (polyuria, renal tubular acidosis, and hyponatremia), and the occurrence of urinary calculi or acute pyelonephritis. Treatment in these patients results in return of normal tubular function if undertaken early. Bilateral complete obstruction causes acute renal failure of the postrenal type and leads rapidly to death unless corrected. This is therefore a medical emergency.

Urinary Calculi (Urolithiasis)

Urolithiasis is a common clinical problem, occurring in about 0.5–2% of the general population (accounts for one of every 1000 hospital admissions in the United States). Urinary calculi may form in any part of the urinary tract, but the vast majority form in the renal pelvis (renal calculi) or bladder.

Etiology & Classification

(Table 50-1)

Seventy percent of patients with urinary calculi have calcium oxalate calculi. In most of these patients, there is no biochemical abnormality to account for the calculi. Hypercalciuria or hyperoxaluria is present in a minority of patients. Calcium oxalate calculi are small, hard calculi with jagged edges that damage the ureteral mucosa as they pass downwards. Phosphate calculi (also called “struvite” or “triple” calculi) account for 15% of urinary calculi and tend to be associated with urinary infections caused by urea-splitting organisms such as Proteus, which produce ammonia and make the urine alkaline. Alkalinity of the urine is necessary for formation of phosphate calculi. These tend to be solitary, large, and soft and may fill the pelvicaliceal system (staghorn calculus; Figure 50-3). Uric acid calculi (10%) are important because they are radiolucent and therefore not seen on plain abdominal x-rays.

Clinical Features

Calculi typically present with acute ureteral obstruction, ureteral colic, and hematuria due to mucosal trauma. Small stones are successfully pushed down the ureter by peristalsis into the bladder and then passed out with urine.

Urinary tract obstruction occurs when a stone becomes impacted in the ureter. Hydronephrosis, urinary stasis, urinary tract infection, and acute pyelonephritis commonly follow.

Diagnosis of ureteral calculi is made by plain x-ray (radiopaque calculi) or intravenous or retrograde pyelography (radiolucent stones). Ninety percent of urinary calculi are radiopaque (Table 50-1). Serum and urinary studies are necessary to identify a predisposing cause (hypercalcemia, hyperoxaluria, cystinuria, gout, urinary infection). It should be noted that the presence of crystals in the urine does not correlate with the presence of urinary calculi.

Treatment

Treatment of ureteral calculi consists of observation of the stone as it passes down the ureter, combined with alleviation of pain. With large and impacted calculi, lithotripsy to ultrasonically fracture the stones—or surgery to remove them—is indicated.

Structure & Function

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.

Congenital Anomalies

Anatomic Abnormalities

Anatomic abnormalities such as duplication—complete or incomplete—and congenital fistulas caused by abnormal development of the cloaca and urogenital sinus are rare.

Urachal Abnormalities

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.

Inflammatory Lesions

Acute Cystitis

Etiology

Acute Bacterial Cystitis

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.

Acute Radiation Cystitis

Radiation cystitis occurs in cases where the bladder is included in the field of pelvic irradiation for malignant neoplasms.

Drug Effects

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.

Pathology

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.

Clinical Features

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 & Treatment

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.

Tuberculosis

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.

Schistosomiasis

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

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.

Miscellaneous Diseases

Bladder Diverticula

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

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.

Bladder Calculi

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.

Neoplasms of the Bladder

Urothelial Neoplasms

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).

Etiology

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.

Pathology

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).

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.

1. 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.

2. 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.

3. 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.

4. 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.

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.

Clinical Features

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.

The diagnosis is made by cystoscopy and biopsy.

Clinical Staging

Clinical staging depends on the degree of invasion by the neoplasm and the presence of lymph node and distant metastases (Table 50-2).

Treatment & Prognosis

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

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.

Nonepithelial Neoplasms

Paraganglioma (Pheochromocytoma)

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

Mesenchymal neoplasms are rare. Smooth muscle tumors (leiomyoma and leiomyosarcoma) are the most common of these; embryonal rhabdomyosarcoma occurs in young children.

Congenital Anomalies (Posterior Urethral Valve)

Posterior urethral valve is a congenital anomaly that occurs mainly in males. It is characterized by the presence of folds of mucous membrane in the posterior urethra that cause partial valvular obstruction to the passage of urine, leading to infection and hydronephrosis in childhood.

Urethral Infections (Urethritis)

Most infections of the urethra are sexually transmitted. Gonorrhea and nonspecific urethritis, which is caused by numerous organisms, including chlamydiae, are the most common. These infections are discussed in Chapter 54: Sexually Transmitted Infections.

Urethral strictures may follow chronic infections and urethral trauma. When severe, urinary flow is obstructed.

Urethral Neoplasms

Urethral Caruncle

A caruncle is a common lesion of the urethra, occurring mainly in older women. It usually presents as a small (< 2 cm) nodular, red, friable mass situated at the external urethral orifice. It frequently becomes ulcerated and bleeds.

Microscopically, a urethral caruncle is composed of inflamed, highly vascular granulation tissue. The cause is uncertain, but it is more apt to be a reactive change than a neoplasm.

Surgical excision is curative.

Carcinoma of the Urethra

Urethral carcinoma is extremely rare. The most common form is transitional cell carcinoma of the prostatic urethra in males. Lower urethral carcinomas are highly malignant, frequently squamous carcinomas or adenocarcinomas. These have a very poor prognosis, with a 5-year survival rate close to zero.