URETER DISEASE

ANATOMY

The ureters are the ducts that carry urine from the kidneys to the urinary bladder, passing anterior to the psoas major. The ureters are muscular tubes that can propel urine along by the motions of peristalsis. In the adult, the ureters are usually 2530cm long. In humans, the ureters enter the bladder through the back, running within the wall of the bladder for a few centimetres. There are no valves in the ureters, backflow being prevented by pressure from the filling of the bladder, as well as the tone of the muscle in the bladder wall. In the female, the ureters pass through the mesometrium on the way to the urinary bladder.

HISTOLOGY

The ureter has a diameter of about 3 millimeters, and the lumen is star-shaped. Like the bladder, it is lined with transitional epithelium, and contains layers of smooth muscle. The epithelial cells of the ureter are stratified (in many layers), are normally round in shape but become squamous (flat) when stretched. The lamina propria is thick and elastic (as it is important that it is impermeable). There are two spiral layers of smooth muscle in the ureter wall, an inner loose spiral, and an outer tight spiral. The inner loose spiral is sometimes described as longitudinal, and the outer as circular, (this is the opposite to the situation in the gastrointestinal tract). The distal third of the ureter contains another layer of outer longitudinal muscle. The adventitia of the ureter, like elsewhere is composed of fibrous connective tissue, that binds it to adjacent tissues.

URETER DISEASE
Congenital Inflamation Tumor Obstruction

Congenital Disease

1. Duplex (duplicated) system

The duplex system is a renal unit in which the kidney has 2 pelvicaliceal systems. A patient with a duplication anomaly may have a single ureter with a duplicated collecting system, bifid ureters (partial or incomplete duplication), or 2 ureters that empty separately into the bladder (complete duplication). The upper ureter is more likely to be associated with ectopic insertion, ureterocele, and/or obstruction, whereas the lower ureter is frequently associated with vesicoureteral reflux (VUR). The upper (lower) pole is one of the components of the duplex kidney. The upper (lower)-pole ureter drains the upper (lower) pole of a duplex kidney. Caudal or medial ectopia describes the ureteral orifice when located at the proximal lip of the bladder neck or beyond.

2. Ectopic ureter

Ectopic ureter occurs when the ureter drains to an abnormally located (ectopic) orifice. Bilateral single-system ureteral ectopia is rare and usually coexists with a multitude of other urinary tract abnormalities (eg, VUR, renal dysplasia, rudimentary bladder development).

3. Megaureter

A megaureter is a wide ureter. Megaureters may be classified as obstructed, refluxing, obstructed and refluxing, and nonobstructed/nonrefluxing.

Etiology of Megaureter

Primary obstructing megaureter is caused by a structural alteration in the muscular layers of the distal ureter, which is characterized, to varying degrees, by diminished or absent longitudinal muscle fibers, hypertrophied or hyperplastic circular muscle fibers, or increased connective tissue deposition. These changes are defined pathologically and may represent either an arrest of normal development or an intrauterine response of the ureter to ongoing obstruction. Animal models of congenital megaureter are lacking, but Mortell et al have developed a rat model of prenatal doxorubicin (Adriamycin) exposure that may help elucidate the etiology of this developmental defect.

Pathophysiology of Megaureter

Partial obstruction in the abnormal distal segment of the ureter leads to progressive dilatation. Progression to hydronephrosis (ie, dilation of the renal pelvis and calyces) occurs when the ureter no longer accommodates resistance to urinary drainage; pressure is then conveyed more proximally. Complete obstructions are rare and are invariably associated with a nonfunctioning renal unit at diagnosis. Primary obstructed megaureters enter the bladder in a normal location on the trigone, with the ureteral orifice appearing unaffected. This entity should not be confused with ectopic megaureters that end in

Clinical presentation of primary megaureter

Includes the following: UTI Hematuria Pyuria Flank mass Failure to thrive Sepsis Fever of unknown origin Abdominal or pelvic pain Abdominal mass Urolithiasis Serendipitous identification on imaging (eg, ultrasonography ; CT scanning; kidneys, ureters, and bladder [KUB] radiography; bone scan)

Light microscopic findings in primary obstructive megaureters. A, Operative exposure. B, Specimen; note that the obstructed segment often admits a catheter or probe. C, Longitudinal section showing no abnormally. D, Reduced muscle bulk seen in some megaureters. E, Circular muscle preponderance. F, Thickened adventitia. Various abnormalities are encountered with light microscopy.

Electron microscopic findings in primary obstructive megaureter. A, Operative specimen. B, Muscle cell atrophy, absent nexus, and excessive collagen and ground substance in the intercellular space from dilated ureter. C, Abnormal collagen fibers between muscle cells reduced from x 4000. D, Abnormality reduced from x 17,000 from narrow ureter.

4. Ureterocele

A ureterocele is a congenital saccular dilatation of the distal segment of the ureter. This anomaly usually involves the upper pole of a duplex system. The ureter inserts ectopically (ectopic ureterocele) but may involve a single system. In this case, the ureter usually inserts within the bladder (orthotopic ureterocele). Ureteroceles may be associated with obstruction and VUR.

Etiology of Uterocele

The precise embryologic etiology of the ureterocele has been greatly debated. Several theories exist, including obstruction of the ureteral orifice, incomplete muscularization of the intramural ureter, and excessive dilation of the intramural ureter during the development of the bladder and trigone. The most commonly accepted theory behind ureterocele formation is the obstruction of the ureteral orifice during embryogenesis, with incomplete dissolution of the Chwalla membrane. (The Chwalla membrane is a primitive thin membrane that separates the ureteral bud from the developing urogenital sinus.) Failure of this membrane to completely perforate during development of the ureteral orifice is thought to explain the occurrence of a ureterocele.

Pathophysiology of Uterocele

It is important to make a distinction between orthotopic and ectopic ureteroceles since therapeutic options and outcomes differ between these two clinical entities. The development of an ectopic ureterocele is best explained by reviewing the embryogenesis of the kidney and ureter.

Clinical symptoms of ureteroceles

May include the following: Urinary tract infection Urosepsis Obstructive voiding symptoms Urinary retention Failure to thrive Hematuria Cyclic abdominal pain Ureteral calculus

Intravenous urogram demonstrating left hydroureteronephrosis due to a ureterocele represented by the round filling defect located at the left base of the bladder

5. Vesicoureteral reflux

VUR is defined as retrograde regurgitation of urine from the urinary bladder up the ureter and into the collecting system of the kidneys. The International Reflux Grading system classifies VUR into 5 grades, depending on the degree of retrograde filling and dilation of the renal collecting system. This system is based on the radiographic appearance of the renal pelvis and calyces on a voiding cystogram, as follows: Grade I: Urine backs up into the ureter only, and the renal pelvis appears healthy, with sharp calyces. Grade II: Urine backs up into the ureter, renal pelvis, and calyces. The renal pelvis appears healthy and has sharp calyces. Grade III: Urine backs up into the ureter and collecting system. The ureter and pelvis appear mildly dilated, and the calyces are mildly blunted. Grade IV: Urine backs up into the ureter and collecting system. The ureter and pelvis appear moderately dilated, and the calyces are moderately blunted. Grade V: Urine backs up into the ureter and collecting system. The pelvis severely dilates, the ureter appears tortuous, and the calyces are severely blunted.

Megaureter with reflux. A, Light microscopy shows attenuated musculature of intravesical ureter. B, Electron microscopy shows normal muscle cells of the juxtavesical ureter reduced from x 3000. C, Electron microscopy shows intravesical ureter with decreased muscle cell population.

INFLAMATION

Ureteritis is infection of one or both ureters, the tubes that connect the kidneys to the bladder. The spread of an infection from the kidneys or bladder is the most common cause of ureteritis. Another cause is a slowing of the flow of urine because of a defective nerve supply to part of the ureter. An underlying kidney or bladder infection is treated with an antibiotic. The sections of the ureter in which nerves are defective may need to be removed surgically.

Ureteritis cystica

In this example of ureteritis cystica, the ureteral lumen has been opened longitudinally. Several fluid-filled vesicles are seen on the urothelial surface.

TUMOR

Frequency

The mean age of occurrence is 65 years. Incidence of TCC increases with age. Moreover, tumors rarely are found at autopsy. Upper tract urothelial tumors occur more frequently in men, with a male-to-female ratio of 3:1. Upper tract urothelial tumors occur more frequently in white people as compared to black people, with a white-to-black ratio of 2:1. An association exists between upper tract TCC and Balkan nephropathy. Balkan nephropathy is a degenerative interstitial nephropathy that confers a 100- to 200-times greater increase in the incidence of upper tract TCC in individuals from rural Balkan areas relative to that observed in individuals residing in neighboring communities. Tumors generally are low grade, multiple, and bilateral compared with TCC of other etiologies.

Etiology

Tobacco smoking is the factor most strongly associated with upper tract TCC and confers a greater than 3-fold increase in risk. Estimates point to smoking as the cause of 70% of upper tract tumors in men and 40% in women. Drinking coffee causes a slight increase in risk of upper tract TCC. This tends to be observed in people who consume more than 7 cups of coffee per day. Analgesic abuse also is a risk factor for urothelial malignancy. It is independent and synergistic with renal papillary necrosis. Long-term exposure to analgesics induces a nephropathy that is associated with an incidence of upper tract TCC as high as 70%. The pathognomonic finding for analgesic abuse, called capillarosclerosis, is found in 15% of patients with upper tract tumors. Occupational exposure to agents utilized in the petrochemical, plastic, and tar industries has been linked to increased risk of TCC.

Chronic infections, irritation, and calculi also may predispose a patient to develop squamous cell carcinoma and, less commonly, adenocarcinoma of the upper urinary tract. Cyclophosphamide has been linked to the development of urothelial tumors. More specifically, a breakdown metabolite called acrolein is thought to be the causative agent. When implicated, the associated tumors tend to be high grade. Finally, heredity may play a part in the development of TCC. An association exists with Lynch syndrome II, a syndrome that includes the early onset of proximal colonic nonpolyposis tumors, numerous synchronous and metachronous

Problem

Upper tract urothelial tumors of the renal pelvis and ureters are relatively rare. Tumors of the renal pelvis account for approximately 10% of all renal tumors and approximately 5% of all urothelial tumors. Ureteral tumors are even more uncommon, occurring with one quarter the incidence of renal pelvis tumors. Transitional cell carcinoma (TCC) accounts for more than 90% of upper tract urothelial tumors.

Pathophysiology

Upper tract tumor types TCC is the most common histology observed, accounting for greater than 90% of upper tract urothelial tumors. TCCs are strongly associated with smoking. Squamous cell carcinoma comprises 1-7% of upper tract urothelial tumors. Squamous cell carcinoma frequently is associated with infected staghorn calculi that have been present for a long duration. Affected patients frequently present with moderately to poorly differentiated tumors and advanced disease. Adenocarcinoma is observed in less than 1% of upper tract tumors. Patients with adenocarcinoma of the upper tracts also may have associated calculi and long-term obstruction, suggesting an etiologic origin for these processes. Inverted papilloma is an unusual lesion. This generally is considered a benign histologic lesion, but it may harbor foci of malignant change.

Urothelial Carcinoma involving Ureter

A nephroureterectomy specimen showing bulbous expansion of proximal ureter near the renal pelvis caused by papillary urothelial carcinoma.

Transitional cell carcinoma (TCC)

OBSTRUCTION

Ureteropelvic Junction Obstruction

Problem: UPJ obstruction is defined as an obstruction of the flow of urine from the renal pelvis to the proximal ureter. The resultant back pressure within the renal pelvis may lead to progressive renal damage and deterioration. UPJ obstruction presents most frequently in childhood, but adults and elderly individuals also can present with a primary obstructive lesion. In adults, other etiologies for ureteral obstruction must be considered, including stones, ureteral compression from extrinsic processes, retroperitoneal fibrosis, and other inflammatory processes.

ETIOLOGY

Possible etiologies for UPJ obstruction include the following: Intrinsic obstruction may occur secondary to stenosis from scarring of ureteral valves. Ureteral hypoplasia may result in abnormal peristalsis through the UPJ. Asymmetry of ureteral wall musculature may inhibit the natural peristaltic emptying of the renal pelvis into the ureter. Abnormal or a high insertion of the ureter into the renal pelvis may cause an altered configuration and impaired drainage of urine. This may be an effect rather than a cause because the 2 etiologies mentioned previously may present with a high-insertion variant seen on imaging studies. Crossing lower pole renal vessel(s) or entrapment of the ureter by a vessel can prohibit urinary flow down the ureter. Vessels that wrap around the UPJ may be associated with obstruction or can be a product of renal dilation and hydronephrosis that distorts renal vascular architecture.

Rotation of the kidney, such as renal ectopy, and renal hypermobility can cause intermittent obstruction that is solely dependent on the position of the kidney relative to the ureter. This was once a very popular diagnosis, but today, the other aforementioned etiologies are more prevalent and this cause is particularly rare. Secondary UPJ obstruction can be caused by prior surgical intervention for other disorders, such as renal stone disease or failed repair of a primary UPJ obstruction. This obstructive lesion most commonly is secondary to ureteral wall and periureteral scar formation. The above abnormalities all cause impaired drainage of urine from the kidney into the ureter, resulting in elevated intrarenal back pressure, dilation of the collecting system, and hydronephrosis.

Intravenous pyelogram demonstrating a ureteropelvic junction obstruction with dilation of the collecting system and lack of excretion of contrast

Retrograde pyelogram demonstrating a ureteropelvic junction obstruction secondary to annular stricture.