{14941} normal urothelium
{14937} normal ureter histology
{10022} normal urothelial, cytology

A STRICTURE is fibrous tissue partially or totally occluding the lumen of a narrow hollow organ, usually the ureter or urethra. They may be congenital, but is more often post-injury scarring (gonorrhea, instrumentation, stone).

URETER PROBLEMS

You know the anatomy. The muscle is interlaced, without real layers. Acute obstruction causes renal colic, which is often excruciating. Chronic obstruction is usually asymptomatic, though the kidney won't function and will eventually atrophy.

Places where stones, etc., hang up are (1) the pyelo-ureteric junction; (2) the pelvic brim; (3) the ureterovesical junction.

DOUBLE URETER (bifid ureter) is whole or partial duplication, with two pelvises in the kidney. No big deal. A few percent of folks have this minor variant.

{15711} bifid ureter, gross

Any obstruction to urinary flow (in the ureter or elsewhere) during fetal life will result in CYSTIC DYSPLASIA of the portion of the kidney that isn't being properly drained.

An INCOMPETENT URETEROVESICAL VALVE is a common birth defect that causes reflux and predisposes to kidney infections. It may stay open all the time, or open during micturition.

This is a very important cause of kidney failure in children.

How to manage these children remains controversial. Many of these children undergo surgical repair, but the benefit of surgery over simply treating infection is not clear (Lancet 357: 1329. 2001). When there is actual deformity of the ureter, the kidney disease is a mix of renal dysplasia (which is part of the birth defect) and actual damage from the bacterial infections.

* This has found recent support in studies of the familial form of the illness: J. Urol. 176: 1842, 2006.

* A variety of defects have been reported in valves that merely reflux during micturition, including findings as simple as lack of smooth muscle and as complicated as the lack of certain obscure electrical cells and their gap junction protein (J. Urol. 174: 1981, 2005.)

HYDROURETER (i.e., dilated ureter) has several causes

CONGENITAL

• the nerve plexus did not form properly
• the muscle in the distal ureter is woven oddly
• the ureterovesical valve doesn't work at all

PREGNANCY ("estrogen relaxes smooth muscle", etc.)

OBSTRUCTION

• Stones
• Fibrous scar ("stricture" if inside the ureter)
• Tumor (inside or outside)

Ureter cancer
Bladder cancer
Prostate cancer
Cervix cancer
Metastases in the para-aortic lymph nodes
Etc.

• Blood clot
• Endometriosis
• Retroperitoneal fibrosis ("sclerosing retroperitonitis", a "fibromatosis" problem, idiopathic or caused by methysergide, the old-time migraine remedy)

CHAGAS'S DISEASE

{18791} pyelonephrosis and pyoureters, gross

A very large ureter is called a MEGA(LO)URETER.

* "Follicular ureteritis" is an archaic name for big lymph nodules. "Ureteritis cystica" and "Brunn's nests" match their counterparts in the urinary bladder.

Almost all cancer of the ureter is "urothelial carcinoma", a better term than the old name "transitional cell carcinoma". Like cancer of the renal pelvis, this is a variation on bladder cancer, with the same risk factors and the same tendency to arise multifocally over the urothelium.

{10580} urothelial carcinoma, ureter

NON-NEOPLASTIC DISEASE OF THE URINARY BLADDER

You learned in physiology and neuroscience class about the various problems with voiding when the cerebral cortex and bladder are separated. When the bladder is inflamed, urinating can be uncomfortable, and often the bladder contracts with excessive force (urgency). See "Big Robbins" for a common-sense list of causes of bladder outlet obstruction.

Anatomic and clinical pathology have not explained "overactive bladder", a common problem especially in older women, with discomfort, frequency, urgency, and/or urge incontinence.

EXSTROPHY of the urinary bladder results from failure of the pubis to form properly. This is a messy problem for the surgeon to repair, and of course, infection and poor hygiene are terrible problems. Update Urol Clin. N.A. 31: 417, 2004. Thankfully, today most of these patients are spared kidney damage despite the risk of ascending infections (J. Urol. 168: 2579, 2002).

{10742} exstrophy of the urinary bladder

PERSISTENT URACHUS, if it is or becomes patent, results in urine dribbling out the navel. More often, urachal cysts remain. When an adenocarcinoma arises deep in the front of the bladder wall, it has probably arisen from urachal remnants.

CYSTOCELE is drooping of a portion of the urinary bladder downward into the more caudal areas of the pelvis. This usually follows childbirth. This may remain filled with urine after voiding, or obstruct the outlet, inviting infection in either case.

HYPERTROPHY OF THE BLADDER WALL results from obstruction, usually from prostatism. The muscle bundles ("trabeculae") become much more visible ("trabeculation").

{24445} hypertrophy of the bladder from prostatism, gross

DIVERTICULA OF THE BLADDER may be congenital, but more often result from a portion of the mucosa pooching out ("pulsion diverticulum") between two strands of hypertrophied muscle in a person suffering from chronic obstruction. This may produce the famous "double urination" (* pis à deux, they call it in France), and/or a place for stasis, inviting infection, and/or a place where bladder stones can form.

Purists: Obviously pulsion diverticula of the bladder are pseudodiverticula, just like in the colon.

If a cancer forms here, it has been considered very serious, since there is no muscularis propria (detrusor) to slow the invasion. New numbers with fairly good survival statistics (i.e., it's the malignant potential of the tumor rather than the presence or absence of a barrier): Urol. 50: 697, 1997; J. Urol. 170: 1761, 2003.

BLADDER STONES usually result from infection, and are composed of magnesium ammonium phosphate.

{21030} bladder stones

Bladder Inflammation From Chile In Spanish

Acute cystitis WebPath Photo

Bladder stones WebPath Photo

CYSTITIS is usually of bacterial origin, and has the same story as common pyelonephritis, which it precedes. Urosepsis still kills many adults of both sexes.

The pathology is what you'd expect. Neutrophils abound in the acute phase. In longstanding disease, there is a chronic inflammatory infiltrate and there may be much fibrosis.

Vitamin C is occasionally still recommended by "natural healing" types to prevent bladder infections. It failed the most recent controlled study miserably (Spinal Cord 34: 592, 1996); eleven years later, there's been no more work on the subject.

* The uncommon "emphysematous cystitis" is an unfortunate term for infections with bugs that have formed gas (South. Med. J. 91: 785, 1998). "Bullous cystitis" is an archaic term for a bladder infection with so much edema between the epithelium and the muscularis propria that it looks like water balloons.

"Encrusted cystitis" is fairly common nowadays, and is due to urea-splitters. It features magnesium ammonium phosphate plastered over the bladder mucosa. Almost all cases are caused by Corynebacterium urealyticum, and this is becoming a bane of the renal transplant service (Eur. Uro. 39: 446, 2001).

* All about symptomatic urinary tract infections on young women, with the risk factors of recent intercourse, use of diaphragm and spermicide, and past history of urinary tract infections: NEJM 335: 468, 1996 (still great).

During the 1980's, there was a push to antibiotic-treat all little girls with asymptomatic bacteriuria, often for a long time. This never made much sense to me and now it's not much discussed.

The folk wisdom that cranberry juice prevents and helps cure bladder infections is clearly true (JAMA 271: 751, 1994, others). It prevents E. coli from forming fimbriae (J. Urol. 159: 559, 1998), so they cannot bind to their sanctuaries on the bladder mucosa. It's the proanthocyanidins (NEJM 339: 1085, 1998).

*  POLYPOID CYSTITIS is not a tumor at all, but a reactive overgrowth (collagen and/or extra ground substance) in response to ongoing inflammation (usually an indwelling catheter). It may be bullous (i.e., look like blobs) or papillary (i.e., look like weeds). Update Int. Urol. 34: 293, 2002.

If it's not inflamed, it's probably a fibroepithelial polyp instead (Am. J. Surg. Path. 29: 460, 2005), a benign tumor of alarming appearance.

CHEMOTHERAPY CYSTITIS results from cyclophosphamide ("Cytoxan") or busulfan ("Myleran") administration, and RADIATION to the pelvic area can also produce a vicious cystitis.

A really bloody-looking cystitis ("hemorrhagic cystitis") should make you think of cyclophosphamide toxicity. Adenovirus infections in the very immunocompromised can also be bloody; they are now treatable with antivirals. * Future pathologists: You'll learn to recognize "cytoxan cells", which have big hyperchromatic nuclei and scanty cytoplasm, but smudgy nuclear chromatin that lets you know they're not cancer. Review of the histopathology of chemotherapy cystitis: Am. J. Surg. Path. 28: 909, 2004.

* "Giant cell cystitis" should not be diagnosed. It's an old term for the presence of of giant urothelial cells in patients who have had radiation or chemotherapy.

HUNNER'S INTERSTITIAL CYSTITIS ("painful bladder syndrome") (Urology 49(5A): 14, 1997; Am. Fam. Phys. 64: 1199, 2001) is a poorly-understood process in which all three layers of the bladder become chronically inflamed.

Patients are mostly women, and they often have considerable pain and urgency. The pain must be due, at least in part, to excess permeability of the urothelium to the potassium in the urine (Urology 57: 428, 2001; the same is apparently true of the equally-mysterious, painful "urethral syndrome".)

Probably the bladder epithelium becomes over-permeable, but morphologic changes are not obvious and the altered molecular structure is only now being worked out by pathologists (J. Urol. 171: 1554, 2004; Am. J. Clin. Path. 125: 105, 2006.)

Visible on cystoscopy are distinctive new-vessel formations ("glomerulations" cited above) that are now considered important in establishing the diagnosis clinically.

No histopathologic lesion is diagnostic. However, pathologists are now looking at several distinctive findings, each correlating with severity, and each requiring special stains.

A marked increase in mast cells showing signs of activation (J. Urol. 163: 1009, 2000; this is now a robust finding and basis for experimental therapies.) Stain with tryptase.

A different pattern of cytokeratins in the epithelium, without any diffence in morphology (Am. J. Clin. Path. 125: 105, 2006).

VEGF and other stains showing the glomerulations (J. Urol. 172: 945, 2004), and S100 to demonstrate an often-striking increase in little nerve fibers in the mucosa (J. Urol. 177: 142, 2007).

No special stains are required to show the mucosal edema, hemorrhage, epithelial loss and/or granulation tissue in severe cases.

"Hunner's ulcer" is the advanced stage, with mucosal breakdown.

MALAKOPLAKIA is a curious macrophage-rich response to proteus infections. The cells seem to have some problem phagocytizing the bugs.

Grossly, you'll see soft ("malakos" in Greek) yellow plaques.

Microscopically, you'll see foamy, lipid-laden (* "von Hensemann's) macrophages with calcified spherules ("Michaelis-Gutmann bodies"). Nobody knows much about this.

* The cure is to use an antibiotic that penetrates macrophages (Lancet 339: 148, 1992); quinolones seem best (Arch. Int. Med. 156: 577, 1996).

{25276} malakoplakia, histology
{24004} malakoplakia, Michaelis-Gutmann bodies

BRUNN'S NESTS are little balls of urothelial-type cells in the lamina propria of the bladder. They are very common and probably mean nothing. Look for them and you'll probably find them in most bladders. CYSTITIS CYSTICA is like Brunn's nests, only with a hole in the middle. This is supposedly a Brunn's nest that is responding to irritation. In CYSTITIS GLANDULARIS, the cells of cystitis cystica produce mucin; if there are goblet cells, the pathologist will note "with intestinal metaplasia". These are all pathologists' curiosities rather than something to worry about, but you need to know the names as they will often appear on biopsy reports.