Renal Exam 3 Physiology and Pathology

what are the morphologic patterns of bladder tumors?

2 precursor lesions: - noninvasive papillary tumors (begin low grade) - flat noninvasive urothelial carcinoma = carcinoma in situ (start HIGH grade) Invasive carcinoma (a progression of the above)

what are the most common precursor lesions to invasive urothelial carcinoma (although most don't progress to invasive)?

noninvasive papillary tumors *originate from papillary urothelial hyperplasia. These tumors have a range of atypical changes, and are graded according to their biologic behavior. The other precursor lesion to invasive carcinoma, flat noninvasive urothelial carcinoma is referred to as carcinoma in situ, or CIS.

as a response to injury, the urothelium is often replaced by __________, which is a more durable lining (= squamous metaplasia)

nonkeratinizing squamous epithelium *This should be distinguished from glycogenated squamous epithelium that is normally found in women at the trigone.

what are the two routes by which bacteria can reach the kidneys?

(1) through the bloodstream (hematogenous infection) (2) from the lower urinary tract (ascending infection) *The hematogenous route is less common and results from seeding of the kidneys by bacteria from distant foci in the course of septicemia or localized infections such as infective endocarditis. Hematogenous infection is more likely to occur in the presence of ureteral obstruction, and in debilitated patients. Typically, in patients receiving immunosuppressive therapy, nonenteric organisms, such as staphylococci and certain fungi and viruses, are involved.

what are three complications of acute pyelonephritis that can be encountered?

- papillary necrosis - pyonephrosis - perinephric abscess

what are the 2 distinct precursor lesions to invasive urothelial carcinoma?

1) noninvasive papillary tumors 2) flat noninvasive urothelial carcinoma *The most common precursor lesions are the noninvasive papillary tumors, which originate from papillary urothelial hyperplasia. These tumors have a range of atypical changes, and are graded according to their biologic behavior. The other precursor lesion to invasive carcinoma, flat noninvasive urothelial carcinoma is referred to as carcinoma in situ, or CIS.

what are the 2 forms of chronic pyelonephritis?

1) reflux nephropathy 2) chronic obstructive pyelonephritis

_________ usually presents with a sudden onset of pain at the costovertebral angle and systemic evidence of infection, such as fever and malaise. There are often indications of bladder and urethral irritation, such as dysuria, frequency, and urgency. The urine contains many leukocytes (pyuria) derived from the inflammatory infiltrate, but pyuria does not differentiate upper from lower urinary tract infection

Acute pyelonephritis *The finding of leukocyte casts, typically rich in neutrophils (pus casts), indicates renal involvement, because casts are formed only in tubules. The diagnosis of infection is established by quantitative urine culture.

________ is often associated with the following: - Urinary tract obstruction, either congenital or acquired - Instrumentation of the urinary tract, most commonly catheterization - Vesicoureteral reflux - Pregnancy - Preexisting renal lesions, causing intrarenal scarring and obstruction - Diabetes mellitus (increased susceptibility to infection, neurogenic bladder dysfunction & more frequent instrumentation) - immunosuppression and immunodeficiency

Acute pyelonephritis *also note - Gender and age. After the first year of life (when congenital anomalies in males commonly become evident) and up to around age 40 years, infections are much more frequent in females. With increasing age the incidence in males rises as a result of prostatic hypertrophy and instrumentation.

by which route are most clinical pyelonephritis cases caused?

Ascending infection

________ is defined by the presence of cytologically malignant cells within a flat urothelium; it may range from full-thickness cytologic atypia to scattered malignant cells in an otherwise normal urothelium, the latter termed pagetoid spread

Carcinoma in situ (CIS, or flat urothelial carcinoma)

________ usually appears as an area of mucosal reddening, granularity, or thickening without an evident intraluminal mass. It is commonly multifocal and may involve most of the bladder surface and extend into the ureters and urethra. If untreated, 50% to 75% of cases progress to invasive cancer

Carcinoma in situ (CIS, or flat urothelial carcinoma) *A common feature shared with high-grade papillary urothelial carcinoma is a lack of cohesiveness, which leads to the shedding of malignant cells into the urine. When shedding is extensive, only a few CIS cells may be left clinging to a largely denuded basement membrane.

__________ may have a silent onset or present with manifestations of acute recurrent pyelonephritis, such as back pain, fever, pyuria, and bacteriuria. These patients receive medical attention relatively late in their disease course because of the gradual onset of renal insufficiency and hypertension.

Chronic obstructive pyelonephritis

_________ is a disorder in which chronic tubulointerstitial inflammation and scarring involve the calyces and pelvis

Chronic pyelonephritis

_________ and ________ are common metaplastic lesions of the urinary bladder in which nests of urothelium (Brunn nests) grow downward into the lamina propria

Cystitis glandularis and cystitis cystica *Here, epithelial cells in the center of the nest undergo metaplasia and take on a cuboidal or columnar appearance (cystitis glandularis), or retract to produce cystic spaces lined by flattened urothelium (cystitis cystica). Because the two processes often coexist, the condition is typically referred to as cystitis cystica et glandularis. In a variant of cystitis glandularis goblet cells are present, and the epithelium resembles intestinal mucosa (intestinal or colonic metaplasia). Both variants are common incidental findings in normal bladders, but they can also arise in the setting of inflammation and metaplasia.

__________, saccular outpouchings of the ureteral wall, are uncommon lesions that may be congenital or acquired. Most are asymptomatic, but urinary stasis within them sometimes leads to recurrent infections. Dilation (hydroureter), elongation, and tortuosity of the ureters may occur as congenital anomalies or as acquired defects.

Diverticula

________ are pouchlike evaginations of the bladder wall that vary from less than 1 cm to 5 to 10 cm in diameter and may be congenital or acquired. Congenital forms may be due to a focal failure of development of the normal musculature or to some urinary tract obstruction during fetal development.

Diverticula *Acquired diverticula are most often seen with prostatic enlargement (hyperplasia or neoplasia), producing obstruction to urine outflow and marked muscle thickening of the bladder wall. The increased intravesical pressure causes outpouching of the bladder wall and the formation of diverticula. They are frequently multiple and have narrow necks located between the interweaving hypertrophied muscle bundles.

________ is a developmental failure in the anterior wall of the abdomen and the bladder, so that the bladder either communicates directly through a large defect with the surface of the body or lies as an opened sac

Exstrophy of the bladder

________ cancers contain dyscohesive cells with large hyperchromatic nuclei. Some of the tumor cells are highly anaplastic; Mitotic figures, including atypical ones, are frequent. Architecturally, there is disarray and loss of polarity. As compared to low-grade lesions, these tumors have a much higher incidence of invasion into the muscular layer, a higher risk of progression, and, when associated with invasion, a significant metastatic potential.

High-grade papillary urothelial cancer

This form of chronic cystitis occurs most frequently in women and is characterized by intermittent, often severe, suprapubic pain, urinary frequency, urgency, hematuria and dysuria, and cystoscopic findings of fissures and punctate hemorrhages (glomerulations) in the bladder mucosa after luminal distention.

Interstitial Cystitis (Chronic Pelvic Pain Syndrome) *The etiology of this troubling condition is unknown, its evaluation and diagnosis remain controversial, and its treatment is largely empiric

________ urothelial cancer may be associated with papillary urothelial cancer, usually high grade, or adjacent CIS.

Invasive *The extent of the invasion into the muscularis mucosae is of prognostic significance, and understaging on biopsy is a significant problem. The extent of spread (staging) at the time of initial diagnosis is the most important factor in determining the outlook for a patient. Almost all infiltrating urothelial carcinomas are high grade, and as a result grading of the infiltrating component is not critical, as opposed to the importance of grading noninvasive papillary urothelial carcinoma.

_________ carcinomas have an orderly architectural and cytologic appearance. The cells are evenly spaced (i.e., maintain polarity) and cohesive. There is a mild degree of nuclear atypia consisting of scattered hyperchromatic nuclei, infrequent mitotic figures predominantly toward the base, and slight variation in nuclear size and shape. These low-grade cancers may recur and, although infrequent, may also invade. Only rarely do these tumors pose a threat to the patient's life.

Low-grade papillary urothelial carcinomas

The macrophages in malackoplakia have an abundant granular cytoplasm due to phagosomes stuffed with particulate and membranous debris of bacterial origin. In addition, laminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes, known as _________ bodies, are typically present within the macrophages.

Michaelis-Gutmann *The unusual-appearing macrophages and giant phagosomes point to defects in the phagocytic function of macrophages, which become overloaded with undigested bacterial products. Similar lesions have been described in the colon, lungs, bones, kidneys, prostate, and epididymis.

_________ is an unusual lesion that results from implantation of shed renal tubular cells at sites of injured urothelium. The overlying urothelium may be focally replaced by cuboidal epithelium, which can assume a papillary growth pattern. Although the lesions are typically less than a centimeter in size, larger lesions have been reported that can produce signs and symptoms that raise a suspicion of cancer. In addition, the tubular proliferation can infiltrate the underlying lamina propria and superficial detrusor muscle, mimicking a malignant process.

Nephrogenic adenoma

what are the steps involved in ascending infection leading to pyelonephritis?

Normal human bladder and bladder urine are sterile; therefore, a number of steps must occur for renal infection to occur: 1) colonization of the distal urethra and introitus (in the female) by coliform bacteria 2) From the urethra to the bladder, organisms gain entrance during urethral catheterization or trauma 3) a mechanism whereby bacteria gets from the bladder to kidney --> Urinary tract obstruction and stasis of urine -->Vesicoureteral reflux (*Although obstruction is an important predisposing factor in ascending infection, it is incompetence of the vesicoureteral valve that allows bacteria to ascend the ureter into the renal pelvis*) -->Intrarenal reflux. Vesicoureteral reflux also affords a ready mechanism by which the infected bladder urine can be propelled up to the renal pelvis and deep into the renal parenchyma through open ducts at the tips of the papillae (intrarenal reflux)

_________ of the bladder, indistinguishable from small-cell carcinomas of the lung, arise in the bladder often in association with urothelial, squamous, or adenocarcinoma

Small-cell carcinomas

________ represent 1% or less of bladder tumors, and are usually seen in younger patients

Papillomas *These tumors typically arise singly as small (0.5 to 2 cm), delicate, structures, superficially attached to the mucosa by a stalk and are referred to as exophytic; The individual finger-like papillae have a central core of loose fibrovascular tissue covered by epithelium that is histologically identical to normal urothelium

__________ cystitis is an inflammatory lesion resulting from irritation of the bladder mucosa. Although indwelling catheters are the most commonly cited culprits, any injurious agent may give rise to this lesion.

Polypoid *The urothelium is thrown into broad bulbous polypoid projections as a result of marked submucosal edema. Polypoid cystitis may be confused with papillary urothelial carcinoma both clinically and histologically

_________ is one of the most common diseases of the kidney and is defined as inflammation affecting the tubules, interstitium, and renal pelvis

Pyelonephritis

_________ is a complication of acute pyelonephritis that is seen when there is total or almost complete obstruction, particularly when it is high in the urinary tract. The suppurative exudate is unable to drain and thus fills the renal pelvis, calyces, and ureter with pus

Pyonephrosis

_________ is often discovered in children when the cause of hypertension is investigated. Loss of tubular function—in particular of concentrating ability—gives rise to polyuria and nocturia. Radiographic studies show asymmetrically contracted kidneys with characteristic coarse scars and blunting and deformity of the calyceal system. Significant bacteriuria may be present, but it is often absent in the late stages.

Reflux nephropathy

this cancer which resembles squamous cancers occurring at other sites make up 3% to 7% of bladder cancers in the United States, but are much more frequent in countries where urinary schistosomiasis is endemic. Pure _________ are nearly always associated with chronic bladder irritation and infection

Squamous cell carcinomas *Mixed urothelial carcinomas with areas of squamous carcinoma are more frequent than pure squamous cell carcinomas. Most are invasive, fungating tumors or are infiltrative and ulcerative. The level of cellular differentiation varies widely, from well differentiated lesions producing abundant keratin to anaplastic tumors with only focal evidence of squamous differentiation.

________ obstruction is a congenital disorder that is the most common cause of hydronephrosis in infants and children. Cases that present early in life are bilateral in 20% of cases, are often associated with other congenital anomalies, and preferentially occur in males. There is agenesis of the contralateral kidney in a minority of cases. In adults, it is more common in women and is most often unilateral.

Ureteropelvic junction (UPJ) *The condition has been ascribed to abnormal organization of smooth muscle bundles at the UPJ, to excess stromal deposition of collagen between smooth muscle bundles, or rarely to congenitally extrinsic compression of the UPJ by renal vessels.

_________ tumors represent about 90% of all bladder tumors and run the gamut from small benign lesions that do not recur to aggressive cancers that are often fatal. Many of these tumors are multifocal at presentation. Though most common in the bladder, all may be seen from the renal pelvis to the distal urethra

Urothelial *can be invasive OR in situ

_________ is the most common and serious congenital anomaly of the bladder

Vesicoureteral reflux *Abnormal connections between the bladder and the vagina, rectum, or uterus may create congenital vesicouterine fistulae

Bacteria are the most common infectious agent in ________ pyelonephritis and induce a prominent neutrophilic inflammatory response; granulomatous interstitial inflammation is characteristic of fungal or mycobacterial infections.

acute

Most cases of cystitis produce nonspecific acute or chronic inflammation of the bladder. In _________ cystitis there is hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate. Patients receiving cytotoxic antitumor drugs, such as cyclophosphamide, may develop hemorrhagic cystitis. Adenovirus infection also causes a hemorrhagic cystitis.

acute

In the early stages of ________, the neutrophilic infiltration is limited to the tubules. The tubular lumens are a conduit for the extension of the infection, and soon, the infection extends to the interstitium and produces abscesses that destroy the involved tubules

acute pyelonephritis

The hallmarks of _________ are patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, neutrophilic tubulitis and tubular necrosis. The suppuration may occur as discrete focal abscesses or large wedge-like areas and can involve one or both kidneys

acute pyelonephritis

_________ is a suppurative inflammation of the kidney caused by bacterial and sometimes viral (e.g., polyomavirus) infection, which can reach the kidney by hematogenous spread or, more commonly, through the ureters in association with vesicoureteral reflux

acute pyelonephritis

_________ of the bladder are rare and histologically identical to those seen in the gastrointestinal tract. Some arise from urachal remnants or in association with extensive intestinal metaplasia

adenocarcinomas

patients with _______ bladder have lost bladder control, despite having intact efferent fibers from the cord to the bladder and despite intact neurogenic connections with the brain

atonic *have lost the micturition reflex cycle because of sensory fiber damage

________ bladder is caused by destruction of sensory nerve fibers which travel through the pelvic splanchnic nerves (parasympathetic)

atonic *micturition reflex contraction cannot occur if the sensory fibers are destroyed, thereby preventing transmission of stretch signals *causes overflow incontinence

_________ bladder is caused by spinal cord damage above the sacral region

automatic *if the spinal cord is damaged above the sacral region but the sacral cord segments are still intact, typical micturition reflexes can still occur; however, they are no longer controlled by the brain; so micturition occurs, but the bladder empties on its own terms (can be referred to as spastic); patients don't know when its coming

The incidence of carcinoma of the ________ is higher in men than in women, in developed than in developing nations, and in urban than in rural dwellers. The male-to-female ratio for urothelial tumors is approximately 3 : 1. About 80% of patients are between 50 and 80 years of age.

bladder *Bladder cancer, with rare exceptions, is not familial

A significant issue is that 50% of invasive _______ cancers present with muscle-invasive disease and have a relatively poor prognosis despite therapy. For tumors detected at an earlier stage, cystoscopy and biopsy are the mainstays of diagnosis. Subsequently, patients are typically followed with additional surveillance cystoscopies to look for tumor recurrence.

bladder *Additionally, cytologic examination of cells obtained from urine samples and tests performed on urine to detect chromosomal abnormalities (aneuploidy of chromosome 3, 7, and 17 and 9p deletions) by fluorescent in situ hybridization (FISH) are also helpful screening measures, particularly for CIS that might be missed by cytoscopy. The major limitation of both FISH and cytologic screening is that they often fail to identify low-grade neoplasms.

________ is a term used to describe epithelial lesions that have the cytologic features of malignancy but are confined to the epithelium, showing no evidence of basement membrane invasion. Such lesions are considered to be high grade.

carcinoma in situ

Persistence of bacterial infection leads to _______ cystitis associated with mononuclear inflammatory infiltrates. Other patterns worthy of brief mention are not always related to infection. Follicular cystitis is characterized by the presence of lymphoid follicles within the bladder mucosa and underlying wall. Eosinophilic cystitis, manifested by infiltration with submucosal eosinophils, typically is a nonspecific subacute inflammation but may also be a manifestation of a systemic allergic disorder.

chronic

_________ pyelonephritis ensues when anatomic anomalies result in urine reflux or urine outflow obstruction; multiple episodes of this injury leads to irregular scarring of the kidney that is typically more prominent at the upper or lower poles where reflux is more common

chronic

in this type of chronic pyelonephritis, recurrent infections are superimposed on diffuse or localized obstructive lesions, leading to repeated bouts of renal inflammation and scarring

chronic obstructive pyelonephritis *the effects of obstruction contribute to the parenchymal atrophy; indeed, it is sometimes difficult to differentiate the effects of bacterial infection from those of obstruction alone. The disease can be bilateral, as with posterior urethral valves, resulting in renal insufficiency unless the anomaly is corrected, or unilateral, as occurs with calculi and unilateral obstructive anomalies of the ureter.

Although several diseases produce chronic tubulointerstitial alterations, only ________ and analgesic nephropathy affect the calyces, making pelvocalyceal damage an important diagnostic clue

chronic pyelonephritis *Chronic pyelonephritis at one time accounted for 10% to 20% of patients in renal transplant or dialysis units, until predisposing conditions such as reflux became better recognized. This condition remains an important cause of kidney destruction in children with severe lower urinary tract abnormalities.

the microscopic changes in _________ involve predominantly tubules and interstitium. The tubules show atrophy in some areas and hypertrophy or dilation in others; Dilated tubules with flattened epithelium may be filled with casts resembling thyroid colloid (thyroidization)

chronic pyelonephritis *Low-power view showing a corticomedullary renal scar with an underlying dilated deformed calyx. Note the thyroidization of tubules in the cortex.

in _________, the kidneys usually are irregularly scarred; if bilateral, the involvement is asymmetric; the microscopic changes involve predominantly tubules and interstitium. The tubules show atrophy in some areas and hypertrophy or dilation in others

chronic pyelonephritis *Dilated tubules with flattened epithelium may be filled with casts resembling thyroid colloid (thyroidization)

The hallmarks of __________ are coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, and flattening of the papillae; the scars vary from one to several and most are in the upper and lower poles, consistent with the frequency of reflux in these sites

chronic pyelonephritis *these characteristics go for both types

All forms of _________ are characterized by a triad of symptoms: (1) frequency, which in acute cases may necessitate urination every 15 to 20 minutes; (2) lower abdominal pain localized over the bladder region or in the suprapubic region; and (3) dysuria—pain or burning on urination

cystitis *The local symptoms of cystitis may be merely disturbing, but these infections may also be antecedents to pyelonephritis

these are common lesions of the urinary bladder in which nests of urothelium (Brunn nests) grow downward into the lamina propria; Here, epithelial cells in the center of the nest undergo metaplasia and take on a cuboidal or columnar appearance (=__________), or retract to produce cystic spaces lined by flattened urothelium (=__________).

cystitis glandularis cystitis cystica *Because the two processes often coexist, the condition is typically referred to as cystitis cystica et glandularis.

what is the most common cause of bladder outlet obstruction in females?

cystocele of the bladder

what is the most common cause of bladder outlet obstruction in males?

enlargement of the prostate gland due to nodular hyperplasia

Bladder cancer accounts for approximately 7% of cancers and 3% of cancer mortality in the United States. About 95% of bladder tumors are of _________ origin, the remainder being mesenchymal tumors

epithelial *Most epithelial tumors are urothelial (transitional cell) type and are thus interchangeably called urothelial or transitional tumors, but squamous and glandular carcinomas also occur.

which urothelial precursor lesion is referred to as carcinoma in situ, or CIS?

flat noninvasive urothelial carcinoma

________ is the term used to describe dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine

hydronephrosis

Obstructive lesions of the urinary tract increase susceptibility to infection and to stone formation, and unrelieved obstruction almost always leads to permanent renal atrophy, termed __________ or obstructive uropathy. Fortunately, many causes of obstruction are surgically correctable or medically treatable

hydronephrosis *Obstruction may be sudden or insidious, partial or complete, unilateral or bilateral; it may occur at any level of the urinary tract from the urethra to the renal pelvis. It can be caused by intrinsic lesions of the urinary tract or extrinsic lesions that compress the ureter.

once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal nerves to the external sphincter to _________ it

inhibit *if this inhibition is more potent in the brain than the voluntary constrictor signals to the external sphincter, urination will occur; if not, urination will not occur until the bladder fills even more and the micturition reflex becomes more powerful

once a micturition reflex begins, it is "self-regenerative;" what does this mean?

initial contraction of the bladder activates the stretch receptors to cause a greater increased in sensory impulses from the bladder and posterior urethra, which causes a further increase in reflex contraction of the bladder--thus, the cycle is repeated again and again until the bladder has reached a strong degree of contraction; then after a few seconds to more than a minute, the self-regenerative reflex begins to fatigue and the regenerative cycle of the micturition reflex ceases, permitting the bladder to relax

how does the bladder receive sympathetic innervation, and from what levels?

levels L1 & L2 via the inferior hypogastric plexus *sympathetic fibers stimulate mainly blood vessels but may send sensory signals involving fullness or pain

Papillary urothelial neoplasms of _______ malignant potential share many histologic features with papilloma, differing only in having thicker urothelium. At cystoscopy, these tumors tend to be larger than papillomas and may be indistinguishable from low- and high-grade papillary cancers. Recurrent tumors usually show the same morphology; progression to tumors of higher grade may occur but is rare.

low

In the bladder, _________ takes the form of soft, yellow, slightly raised mucosal plaques, 3 to 4 cm in diameter, that are filled with large, foamy macrophages mixed with occasional multinucleate giant cells and lymphocytes. The macrophages have an abundant granular cytoplasm due to phagosomes stuffed with particulate and membranous debris of bacterial origin.

malakoplakia *have Michaelis-Gutmann bodies as well, in enlarged lysosomes within the affected macrophages

A distinctive chronic inflammatory reaction that appears to stem from acquired defects in phagocyte function, _________ arises in the setting of chronic bacterial infection, mostly by E. coli or occasionally Proteus species. It occurs with increased frequency in immunosuppressed transplant recipients.

malakoplakia *so this is a special type of cystitis

the _________ reflex is a single complete cycle of: 1) progressive and rapid increase in pressure 2) a period of sustained pressure 3) return of the pressure back to the basal tone of the bladder

micturition

as the bladder fills, many superimposed _________ contractions may begin to appear; they are the result of a stretch reflex initiated by sensory stretch receptors in the bladder wall (especially by receptors in the posterior urethra)

micturition *sensory and motor signals are via the parasympathetic fibers (pelvic splanchnic)

when the bladder is only partially filled, micturition contractions usually relax spontaneously after a fraction of a minute, the detrusor muscles stop contracting, and pressure falls back to baseline; as the bladder continues to fill, the _________ become more frequent and cause greater contractions of the detrusor muscle

micturition reflexes/contractions

In about one half of individuals with invasive bladder cancer, the tumor has already invaded the bladder wall at the time of presentation, and precursor lesions are not detected. It is presumed in such cases that the precursor lesion was destroyed by the high-grade invasive component, which typically appears as a large, frequently ulcerated mass. Although invasion into the lamina propria worsens the prognosis, the major decrease in survival is associated with invasion of the ________.

muscularis propria (detrusor muscle) *Once muscularis propria invasion occurs, there is a 30% 5-year mortality rate.

Obstruction of the bladder ________ is of major clinical importance because of its eventual effect on the kidney

outlet

_________ is a complication of acute pyelonephritis seen mainly in diabetics, sickle cell disease, and in those with urinary tract obstruction

papillary necrosis *usually bilateral but may be unilateral. One or all of the pyramids of the affected kidney may be involved. On cut section, the tips or distal two thirds of the pyramids have areas of gray-white to yellow necrosis; On microscopic examination the necrotic tissue shows characteristic ischemic coagulative necrosis, with preservation of outlines of tubules. The leukocytic response is limited to the junctions between preserved and destroyed tissue

These tumors typically arise singly as small (0.5 to 2 cm), delicate, structures, superficially attached to the mucosa by a stalk and are referred to as exophytic; The individual finger-like papillae have a central core of loose fibrovascular tissue covered by epithelium that is histologically identical to normal urothelium

papillomas

which branch of the autonomic nervous system is responsible for most sensation from the bladder?

parasympathetic *sympathetic fibers stimulate mainly blood vessels and have little to do with sensation or bladder contraction

the principal nerve supply to the bladder is by way of the ________ nerve(s)

pelvic splanchnic *preganglionic fibers go to wall of bladder then short postganglionic go to detrusor muscle

_________ is a complication of acute pyelonephritis and is an extension of suppurative inflammation through the renal capsule into the perinephric tissue

perinephric abscess

what is an emerging viral pathogen causing pyelonephritis in kidney allografts?

polyomavirus *now referred to as polyomavirus nephropathy, is characterized by infection of tubular epithelial cell nuclei, leading to nuclear enlargement and intranuclear inclusions visible by light microscopy (viral cytopathic effect). The inclusions are composed of virions arrayed in distinctive crystalline-like lattices when visualized by electron microscopy. An interstitial inflammatory response is invariably present. Treatment consists of a reduction in immunosuppression.

Both acute and chronic __________ may be caused by infection via the ascending (more common) or hematogenous route. Obstructive lesions of the urinary tract are important predisposing factors

pyelonephritis *associated with UTIs

_________ is a serious complication of urinary tract infections that can affect the bladder, the kidneys and their collecting system

pyelonephritis *Bacterial infections of the lower urinary tract may be asymptomatic (asymptomatic bacteriuria) and often remain localized to the bladder without the development of renal infection. However, lower urinary tract infection can potentially spread to the kidney.

________ is the more common form of chronic pyelonephritic scarring; it occurs early in childhood as a result of superimposition of a urinary infection on congenital vesicoureteral reflux and intrarenal reflux

reflux nephropathy *Reflux may be unilateral or bilateral; thus, the continuous renal damage may cause scarring and atrophy of one kidney or involve both, leading to renal insufficiency. Vesicoureteral reflux occasionally causes renal damage in the absence of infection (sterile reflux), but only when obstruction is severe.

kidney stones are unilateral in about 80% of patients. The favored sites for their formation are within the ________ and in the bladder

renal calyces and pelves (pic) *If formed in the renal pelvis they tend to remain small, having an average diameter of 2 to 3 mm. These may have smooth contours or may take the form of an irregular, jagged mass of spicules. Often many stones are found within one kidney. On occasion, progressive accretion of salts leads to the development of branching structures known as staghorn calculi, which create a cast of the pelvic and calyceal system.

Double ureters are almost invariably associated with totally distinct double _________ or with the anomalous development of a large kidney having a partially bifid pelvis terminating in separate ureters. Double ureters may pursue separate courses to the bladder but commonly are joined within the bladder wall and drain through a single ureteral orifice. Most are unilateral and of no clinical significance.

renal pelves

what is the mechanism of overflow urinary incontinence?

sensory nerve fibers are destroyed (atonic bladder) and the micturition reflex contractions do not occur; instead of emptying periodically, the bladder fills to capacity and overflows a few drops at a time through the urethra

if the spinal cord is damaged above the sacral region but the sacral cord segments are still intact, typical micturition reflexes can still occur; however, they are no longer controlled by the brain; so micturition occurs, but what is the problem?

the bladder empties without signals to or from the brain (patient can neither control nor sense micturition) *called automatic bladder

In the absence of __________, infection usually remains localized in the bladder (once it's made it there). Thus, the majority of individuals with repeated or persistent bacterial colonization of the urinary tract suffer from cystitis and urethritis (lower urinary tract infection) rather than pyelonephritis

vesicoureteral reflux

The selection of treatment for bladder cancer depends on what 3 qualities of the cancer?

the grade, stage, and whether the lesion is flat or papillary *For small, localized low-grade papillary tumors, the diagnostic transurethral resection is the only surgical procedure done. Patients are followed with cystoscopy and urine cytology for the rest of their lives to detect recurrence. Patients at high risk of recurrence and/or progression (CIS; papillary tumors that are high grade, multifocal, have a history of recurrence, or are associated with lamina propria invasion) receive intravesical instillation of an attenuated strain of Mycobacterium bovis called bacillus Calmette-Guérin (BCG). The bacteria elicit a local inflammatory reaction that destroys the tumor. Radical cystectomy is typically reserved for (1) tumor invading the muscularis propria, (2) CIS or high-grade papillary cancer refractory to BCG, and (3) CIS extending into the prostatic urethra and into the prostatic ducts, where BCG will not come into contact with the neoplastic cells. Metastatic bladder cancer responds to chemotherapy, but is not curable with current agents.

Bladder _________ classically produce painless hematuria. This is their dominant and sometimes only clinical manifestation. Frequency, urgency, and dysuria occasionally accompany the hematuria. When the ureteral orifice is involved, pyelonephritis or hydronephrosis may follow.

tumors *About 60% of neoplasms, when first discovered, are single, and 70% are localized to the bladder

_________ bladder results in frequent and relatively uncontrolled micturition; derives from partial damage in the spinal cord or the brainstem that interrupts most of the inhibitory signals; therefore, facilitative impulses passing continually down the cord keep the sacral centers so excitable that even a small quantity of urine elicits an uncontrollable micturition reflex, thereby promoting frequent urination

uninhibited neurogenic

_________ bladder is caused by lack of inhibitory signals from the brain

uninhibited neurogenic *results in frequent and relatively uncontrolled micturition; derives from partial damage in the spinal cord or the brainstem that interrupts most of the inhibitory signals; therefore, facilitative impulses passing continually down the cord keep the sacral centers so excitable that even a small quantity of urine elicits an uncontrollable micturition reflex, thereby promoting frequent urination

the _________ (the canal that connects the fetal bladder with the allantois) is normally obliterated after birth, but it sometimes remains patent in part or in whole. When totally patent, a fistulous urinary tract connects the bladder with the umbilicus. In other instances, only the central region persists, giving rise to cysts, lined by either urothelium or metaplastic glandular epithelium

urachus *urachal cysts account for only a minority of all bladder cancers (0.1% to 0.3%) but 20% to 40% of bladder ADENOCARCINOMAS

The accumulation or aggregation of lymphocytes forming germinal centers in the subepithelial region may cause slight elevations of the ureteral mucosa and produce a fine granular mucosal surface (=_________). At other times the mucosa may become sprinkled with fine cysts varying in diameter from 1 to 5 mm lined by flattened urothelium (=_________)

ureteritis follicularis ureteritis cystica *this is pictured*

The appearance of _________ tumors varies from purely papillary to nodular or flat. Most arise from the lateral or posterior walls at the bladder base. Papillary lesions are red, elevated excrescences ranging in size from less than 1 cm in diameter to large masses up to 5 cm in diameter. Multiple discrete tumors are often present. As noted, the histologic features encompass a spectrum from benign papilloma to highly aggressive anaplastic cancers. Overall, the majority of papillary tumors are low grade.

urothelial

Individuals with __________ tumors, whatever their grade, have a tendency to develop new tumors after excision, and recurrences may show a higher grade. The risk of recurrence and progression is related to several variables, including tumor size, stage, grade, multifocality, prior recurrence rate, and associated dysplasia and/or CIS in the surrounding mucosa

urothelial *Although the term recurrence is used, most of the subsequent tumors arise at different sites from the original lesion. In some instances the recurrences may be entirely independent new tumors, but in other cases they share the same clonal abnormalities as the initial tumor and represent a true recurrence caused (presumably) by shedding and implantation of the original tumor cells at a new anatomic site.

Several factors have been implicated in the causation of ________. Some of the more important contributors include the following: - Cigarette smoking - Industrial exposure to aryl amines - Schistosoma haematobium infections - Long-term use of analgesics (phenacatin) - Heavy long-term exposure to cyclophosphamide - Irradiation

urothelial carcinoma *Between 50% and 80% of all bladder cancers among men are associated with the use of cigarettes. Cigars, pipes, and smokeless tobacco are associated with a smaller risk

once a micturition reflex has occurred but has not succeeded in emptying the bladder, what usually happens to the nervous elements of this reflex?

usually remain in an inhibited state for a few minutes to 1 hour or more before another micturition reflex occurs; as the bladder becomes more an more filled, micturition reflexes occur more and more often and more and more powerfully *so the whole cycle represented by the graph occurs several times without being "felt" -- eventually another reflex occurs involving the pudendal nerve

_________ is most often due to a congenital absence or shortening of the intravesical portion of the ureter, such that the ureter is not compressed during micturition. In addition, it may be acquired by bladder infection itself

vesicoureteral reflux *It is postulated that bacteria themselves or the associated inflammation can promote reflux by affecting ureteral contractility, particularly in children. Vesicoureteral reflux is estimated to affect 1% to 2% of otherwise normal children. Acquired vesicoureteral reflux in adults can result from persistent bladder atony caused by spinal cord injury. The effect of vesicoureteral reflux is similar to that of an obstruction in that there is residual urine in the urinary tract after voiding, which favors bacterial growth.

what is the function of the pudendal nerve in the urinary system?

voluntary control of the external sphincter