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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Clinical Queries -- PubMed from the National Institutes of Health. Take your questions here first.
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Yahoo! Medline lists other sites that may work well for you

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review linked below. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

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QUIZBANK: Lower urinary (all)

OBJECTIVES:

The student will give a reasonable account of the origins, symptoms, signs, epidemiology, and anatomic pathology of the common bladder lesions.

The student will recognize the common cystoscopic and biopsy lesions.

Urinary Tract Malformations From Chile In Spanish

Urinary Bladder Nice case photos Charam M. Ramnani MD

Bladder "Pathology Outlines" Nat Pernick MD

Bladder Exhibit Virtual Pathology Museum University of Connecticut

Lower Urinary Tract Ed's Histology Notes

Urinary Tract Great pathology images Indiana Med School

INTRODUCTION: Easy unit.

{15588} normal bladder, gross
{15771} normal bladder, gross
{15772} normal bladder, gross
{15587} normal bladder and prostate, gross
{15114} normal bladder, histology
{15120} normal bladder, histology
{15326} normal bladder, histology
{25266} normal bladder histology

You remember that normal transitional epithelium (better, "urothelium") is designed to cover surfaces that change their areas rapidly.

Urothelium should be six or fewer cells thick (really, strata of nuclei), perhaps less when the bladder is full. The superficial layer exhibits the famous protective layer of broad, flat "umbrella cells", while the basal layer is famous for its ability to flatten out.

Normally, it takes about a year to replace itself, so you're unlikely to see any mitotic figures until there's serious disease.

* Urothelium usually produces a bit of mucin, which explains those few bubbles in the toilet bowl. Often tumors that arise from urothelium produce mucin also. This does not make them "adenocarcinomas".

When urothelium turns to urothelial papilloma-carcinoma, it tends to do so in multiple places (Nowell's law again). Forty percent of tumors are multiple at presentation. This has a lot to do with "frequent recurrences after surgery".

{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. 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. 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). The kidney disease is a mix of renal dysplasia (which is part of the birth defect) and actual damage from the bacterial infections.

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

Congenital

• the nerve plexus did not form properly
• the muscle in the distal ureter is woven funny
• 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 just 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 a 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 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.

{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 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.

* Polypoid cystitis is not a tumor at all, but a reactive overgrowth (collagen and/or extra ground substance) in response to ongoing inflammation. It may be bullous (i.e., look like blobs) or papillary (i.e., look like weeds).

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).

*The uncommon "emphysematous cystitis" is an unfortunate term for infections with bugs that have formed gas. "Bullous cystitis" has so much edema between the epithelium and the muscularis propria that it looks like water balloons. "Encrusted cystitis" is due to urea-splitters and features magnesium ammonium phosphate plastered over the bladder mucosa.

*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.

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.

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

*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.

*"Giant cell cystitis" is a non-disease, merely describing the presence of giant cells in patients who have had radiation or chemotherapy.

Hunner's interstitial / ulcerative cystitis (Urology 49(5A): 14, 1997) is a poorly-understood process in which all three layers of the bladder become chronically inflamed.

No histopathologic lesion is diagnostic, but most distinctive is a marked increase in mast cells.

Patients are mostly women, and they often have considerable pain and urgency. The pain is probably 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".

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

The disease is poorly understood, difficult to treat, and probably represents a common response to any of a variety of immune (?) problems (J. Urol. 153: 629, 1995). The epithelial cells seem to come apart, and they remain abnormal in culture (J. Urol. 153: 243, 1995).

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. Cystitis cystica is like Brunn's nests, only with a hole in the middle. Both are found in a majority of bladders and mean nothing. In cystitis glandularis, the cells of cystitis cystica produce mucin. These are all pathologists' curiosities rather than something to worry about. They suggest that there's been some inflammation going on.