LOWER URINARY TRACT & MALE GENITAL TRACT SYSTEM
Robbins and Cotran Patho Basis of Disease 10th Ed.
*use at your own risk
TRANS BY: AD, CC, AC
LOWER URINARY TRACT
-renal pelves, ureters, urinary bladder, urethra (except the terminal portion) are lined by a special form of transitional epithelium (UROTHELIUM) composed of 5-6 layers of cells with oval nuclei, often with linear nuclear grooves, and a surface
layer consisting of large, flattened “umbrella cells” with abundant cytoplasm
-the lamina propria in the bladder contains wisps of smooth muscles that form a discontinuous muscularis mucosa
-bladder cancers are stage based on the basis of the invasion of larger muscle bundles of the detrusor muscle (muscularis propria)
-In middle-aged and older women, relaxation of pelvic support leads to prolapse (descent) of the uterus, pulling with it the floor of the bladder. The bladder is protruded into the vagina, creating a pouch (CYSTOCELE) that fails to empty
readily with micturition
DISEASE DESCRIPTION PATHOGENESIS MORPHOLOGY CLINICAL FEATURES TREATMENT
URETERS
CONGENITAL ANOMALIES -ureteropelvic junction (UPJ) obstruction is the most common cause of hydronephrosis in infants and children and preferentially affects males, are bilateral and often associated with other anomalies
-agenesis of the contralateral kidney
-in adults, it is more common in women and unilateral
-abnormal organization of smooth muscle bundles or excess stromal deposition of collagen between smooth muscle bundles at the UPJ, or in rare cases to extrinsic compression of theUPJ
TUMOR AND TUMOR-LIKE -primary tumors of the ureter are rare
LESIONS -benign tumors are generally mesenchymal origin
FIBROEPITHELIAL POLYP
-occurring in children; composed of loose, vascularized connective tissue overlaid by urothelium
-primary malignant tumors resemble those arising in the renal pelvis, calyces and bladder
UROTHELIAL CARCINOMAS
-sixth and seventh decades of life; cause obstruction of the ureteral lumen; occur concurrently with urothelial carcinomas of bladder or renal pelvis
OBSTRUCTIVE LESIONS -may give rise to hydroureter, SCLEROSING RETROPERITONEAL FIBROSIS SCLEROSING RETROPERITONEAL FIBROSIS SCLEROSING
hydronephrosis, and pyelonephritis -elevated levels of serum IgG4 and -fibrous tissue containing a prominent RETROPERITONEAL FIBROSIS
-unilateral obstruction typically fibroinflammatory lesions rich in IgG4-secreting infiltrate of lymphocytes, often with -corticosteroids
results from proximal intrinsic or plasma cells germinal centers, plasma cells (frequently -ureteral stents or surgical
extrinsic causes -drug exposures (ergot derivatives, β-adrenergic IgG4-positive), and eosinophils extrication of the ureters
-bilateral arises from distal causes blockers), inflammatory conditions (vasculitis, from surrounding fibrous
(*see table 21.2) diverticulitis, Crohn disease), or malignancies tissue (ureterolysis)
(lymphomas, urinary tract carcinomas)
SCLEROSING RETROPERITONEAL -no obvious cause and are considered primary or
FIBROSIS idiopathic (ORMOND DISEASE)
-fibrotic proliferative inflammatory
process that encases
retroperitoneal structures and
causes hydronephrosis
-occurs in middle to late age
(males)
1
, URINARY BLADDER
CONGENITAL ANOMALIES VESICOURETERAL REFLUX DIVERTICULA
-most common and serious -small and asymptomatic
congenital anomaly -constitute sites of urinary stasis and
-predisposes to ascending pyelonephritis and loss of renal function predispose to infection and the
-Abnormal connections between formation of bladder calculi
the bladder and the vagina, rectum, or uterus may create congenital vesicouterine fistulae -carcinoma may arise in bladder
DIVERTICULA diverticula; such tumors are on
-pouch-like invaginations of the bladder wall that vary from less than 1 cm to 10 cm in average more advanced in stage
diameter and may be congenital or acquired due to the thin or absent muscularis
-Congenital diverticula may be due to a focal failure of development of the normal propria layer of diverticula
musculature or to a urinary tract obstruction during fetal development
-Acquired diverticula are most
often associated with prostatic hyperplasia, producing urinary outflow obstruction
-increase in intravesical pressure causes outpouching of the bladder
wall and the formation of diverticula
EXSTROPHY OF THE BLADDER
-developmental failure in the anterior wall of the abdomen and the bladder
-bladder communicates directly with the abdominal surface
-exposed bladder mucosa may
undergo colonic glandular metaplasia and is subject to chronic infection that often spreads
to the upper urinary tract
URACHAL ANOMALIES
-urachal canal connects the fetal
bladder with the allantois remains fully or partially patent
-former creates a fistulous urinary tract connection between the bladder and umbilicus
-only a central region of patent urachus persists, a urachal cyst lined by urothelial or
metaplastic glandular epithelium is formed
-increased risk for neoplastic transformation (adenocarcinoma)
INFLAMMATION ACUTE AND CHRONIC CYSTITIS ACUTE CYSTITIS TRIAD OF SYMPTOMS
-Bacterial pyelonephritis is frequently -hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate (1) frequency, which in acute cases may necessitate urination every 15
preceded by infection of the urinary CHRONIC CYSTITIS to 20 minutes
bladder, with retrograde spread of -Persistence of the bacterial infection (2) lower abdominal pain localized over the bladder region or in the
microorganisms into the kidneys and -mononuclear inflammatory infiltrates suprapubic region
their collecting system IATROGENIC CYSTITIS (3) dysuria (pain or burning on urination)
-most common etiologic agents of -receiving systemic chemotherapy or pelvic irradiation
cystitis are the coliforms: Escherichia HEMORRHAGIC CYSTITIS INTERSTITIAL CYSTITIS(CHRONIC PELVIC PAIN SYNDROME)
coli, followed by Proteus, Klebsiella, -Cytotoxic agents, such as cyclophosphamide -an unpleasant sensation (pain, pressure, discomfort) perceived to be
and Enterobacter RADIATION CYSTITIS related to the urinary bladder, associated with urinary tract symptoms
-Women are more likely to develop -following the irradiation of the bladder region of more than six weeks duration, in the absence of infection or other
cystitis as a result of their shorter FOLLICULAR CYSTITIS identifiable causes
urethras -characterized by the presence of lymphoid follicles within the bladder mucosa and underlying -intermittent, often severe, suprapubic pain; urinary frequency; urgency;
-.Tuberculous cystitis is almost always wall hematuria; and dysuria
a sequel to renal tuberculosis EOSINOPHILIC CYSTITIS -mucosal fissures and punctate
-Gas-forming bacteria (such as -infiltration of the submucosa by eosinophils hemorrhages (glomerulations)
Clostridium perfringens) result in -mast cells are often increased in the submucosa
emphysematous cystitis (gas-filled MALAKOPLAKIA - Some cases are associated with chronic mucosal ulcers (Hunner
vesicles in the bladder wall). -soft yellow, slightly raised mucosal plaques, 3 to 4 cm in diameter ulcers); this is termed the late (classic, ulcerative) phase
2
, -aggregates of large foamy macrophages with occasional multinucleate giant cells and -transmural fibrosis may lead to a contracted bladder
lymphocytes
-macrophages have abundant granular cytoplasm MALAKOPLAKIA
-aminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes, - distinctive chronic inflammatory reaction that appears to stem from
known as Michaelis-Gutmann bodies acquired defects in phagocyte function
-chronic bacterial infection, mostly by E. coli or occasionally Proteus
species, and occurs with increased frequency in the setting of
immunosuppression
POLYPOID CYSTITIS
-inflammatory lesion resulting from irritation of the bladder mucosa,
most commonly as a result of instrumentation
-urothelium is thrown into broad bulbous polypoid projections as a
result of marked submucosal edema
METAPLASTIC LESIONS CYSTITIS GLANDULARIS AND CYSTITIS CYSTICA
-nests of urothelium (von Brunn nests) grow downward into the lamina propria
-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)
-glandularis goblet cells are present, and the epithelium resembles intestinal mucosa (intestinal or colonic metaplasia)
SQUAMOUS METAPLASIA
-a response to chronic injury, the
urothelium is often replaced by nonkeratinizing or keratinizing squamous epithelium
-classic example Is seen with bladder schistosomiasis
NEPHROGENIC ADENOMA
-may not be a form of true metaplasia
-at least some of these lesions are caused by implantation and growth of renal tubular cells at sites of bladder mucosa erosion
-overlying urothelium is focally replaced by cuboidal epithelium, which can assume a papillary growth pattern
NEOPLASMS UROTHELIAL NEOPLASMS -Non– muscle-invasive papillary cancers often -Papillary lesions are red, elevated -Painless hematuria is the most -subsequent treatment and
- most common type have gain-of-function alterations that increase excrescences ranging in size from less common symptom course of bladder
-two distinct precursor lesions to signaling through growth factor receptor than 1 cm in diameter to large masses up -Frequency, urgency, and dysuria carcinoma depend on
invasive urothelial carcinoma: pathways, such as amplifications of the FGFR3 to 5 cm in diameter tumor grade and stage
noninvasive papillary tumors and flat tyrosine kinase receptor gene and activating -(non-invasive) small,
noninvasive urothelial carcinoma in mutations in the genes encoding RAS and PI 3- PAPILLOMAS localized low-grade
situ (CIS) kinase -often seen in younger patients papillary tumors, diagnostic
-most common precursor lesions are -majority of muscle-invasive bladder cancers -arise singly as small (0.5 to 2 cm), delicate transurethral resection
the noninvasive papillary tumors, develop by progression from “flat” CIS (mutations structures superficially attached to the -CIS and papillary tumors
which originate from papillary that disrupt the function of p53 and RB) mucosa by a stalk (exophytic papillomas) that are large, high grade,
urothelial hyperplasia -recurrently mutated genes involved in cell cycle -individual finger-like papillae have a multifocal, have a history of
-CIS is a term used to describe regulation, chromatin regulation, DNA repair, and central core of loose fibrovascular tissue recurrence, or are
epithelial lesions that have the growth factor signaling pathways covered by epithelium associated with lamina
cytologic features of malignancy but - -inverted papillomas are completely propria invasion are treated
are confined to the epithelium, benign lesions consisting of inter- with intravesical instillation
showing no evidence of basement anastomosing cords of cytologically of an attenuated strain of
membrane invasion (HIGH GRADE) bland urothelium that extend down into Mycobacterium bovis
-Although invasion into the lamina the lamina propria called bacillus Calmette-
propria worsens the prognosis, the Guérin (BCG)
3
Robbins and Cotran Patho Basis of Disease 10th Ed.
*use at your own risk
TRANS BY: AD, CC, AC
LOWER URINARY TRACT
-renal pelves, ureters, urinary bladder, urethra (except the terminal portion) are lined by a special form of transitional epithelium (UROTHELIUM) composed of 5-6 layers of cells with oval nuclei, often with linear nuclear grooves, and a surface
layer consisting of large, flattened “umbrella cells” with abundant cytoplasm
-the lamina propria in the bladder contains wisps of smooth muscles that form a discontinuous muscularis mucosa
-bladder cancers are stage based on the basis of the invasion of larger muscle bundles of the detrusor muscle (muscularis propria)
-In middle-aged and older women, relaxation of pelvic support leads to prolapse (descent) of the uterus, pulling with it the floor of the bladder. The bladder is protruded into the vagina, creating a pouch (CYSTOCELE) that fails to empty
readily with micturition
DISEASE DESCRIPTION PATHOGENESIS MORPHOLOGY CLINICAL FEATURES TREATMENT
URETERS
CONGENITAL ANOMALIES -ureteropelvic junction (UPJ) obstruction is the most common cause of hydronephrosis in infants and children and preferentially affects males, are bilateral and often associated with other anomalies
-agenesis of the contralateral kidney
-in adults, it is more common in women and unilateral
-abnormal organization of smooth muscle bundles or excess stromal deposition of collagen between smooth muscle bundles at the UPJ, or in rare cases to extrinsic compression of theUPJ
TUMOR AND TUMOR-LIKE -primary tumors of the ureter are rare
LESIONS -benign tumors are generally mesenchymal origin
FIBROEPITHELIAL POLYP
-occurring in children; composed of loose, vascularized connective tissue overlaid by urothelium
-primary malignant tumors resemble those arising in the renal pelvis, calyces and bladder
UROTHELIAL CARCINOMAS
-sixth and seventh decades of life; cause obstruction of the ureteral lumen; occur concurrently with urothelial carcinomas of bladder or renal pelvis
OBSTRUCTIVE LESIONS -may give rise to hydroureter, SCLEROSING RETROPERITONEAL FIBROSIS SCLEROSING RETROPERITONEAL FIBROSIS SCLEROSING
hydronephrosis, and pyelonephritis -elevated levels of serum IgG4 and -fibrous tissue containing a prominent RETROPERITONEAL FIBROSIS
-unilateral obstruction typically fibroinflammatory lesions rich in IgG4-secreting infiltrate of lymphocytes, often with -corticosteroids
results from proximal intrinsic or plasma cells germinal centers, plasma cells (frequently -ureteral stents or surgical
extrinsic causes -drug exposures (ergot derivatives, β-adrenergic IgG4-positive), and eosinophils extrication of the ureters
-bilateral arises from distal causes blockers), inflammatory conditions (vasculitis, from surrounding fibrous
(*see table 21.2) diverticulitis, Crohn disease), or malignancies tissue (ureterolysis)
(lymphomas, urinary tract carcinomas)
SCLEROSING RETROPERITONEAL -no obvious cause and are considered primary or
FIBROSIS idiopathic (ORMOND DISEASE)
-fibrotic proliferative inflammatory
process that encases
retroperitoneal structures and
causes hydronephrosis
-occurs in middle to late age
(males)
1
, URINARY BLADDER
CONGENITAL ANOMALIES VESICOURETERAL REFLUX DIVERTICULA
-most common and serious -small and asymptomatic
congenital anomaly -constitute sites of urinary stasis and
-predisposes to ascending pyelonephritis and loss of renal function predispose to infection and the
-Abnormal connections between formation of bladder calculi
the bladder and the vagina, rectum, or uterus may create congenital vesicouterine fistulae -carcinoma may arise in bladder
DIVERTICULA diverticula; such tumors are on
-pouch-like invaginations of the bladder wall that vary from less than 1 cm to 10 cm in average more advanced in stage
diameter and may be congenital or acquired due to the thin or absent muscularis
-Congenital diverticula may be due to a focal failure of development of the normal propria layer of diverticula
musculature or to a urinary tract obstruction during fetal development
-Acquired diverticula are most
often associated with prostatic hyperplasia, producing urinary outflow obstruction
-increase in intravesical pressure causes outpouching of the bladder
wall and the formation of diverticula
EXSTROPHY OF THE BLADDER
-developmental failure in the anterior wall of the abdomen and the bladder
-bladder communicates directly with the abdominal surface
-exposed bladder mucosa may
undergo colonic glandular metaplasia and is subject to chronic infection that often spreads
to the upper urinary tract
URACHAL ANOMALIES
-urachal canal connects the fetal
bladder with the allantois remains fully or partially patent
-former creates a fistulous urinary tract connection between the bladder and umbilicus
-only a central region of patent urachus persists, a urachal cyst lined by urothelial or
metaplastic glandular epithelium is formed
-increased risk for neoplastic transformation (adenocarcinoma)
INFLAMMATION ACUTE AND CHRONIC CYSTITIS ACUTE CYSTITIS TRIAD OF SYMPTOMS
-Bacterial pyelonephritis is frequently -hyperemia of the mucosa and neutrophilic infiltrate, sometimes associated with exudate (1) frequency, which in acute cases may necessitate urination every 15
preceded by infection of the urinary CHRONIC CYSTITIS to 20 minutes
bladder, with retrograde spread of -Persistence of the bacterial infection (2) lower abdominal pain localized over the bladder region or in the
microorganisms into the kidneys and -mononuclear inflammatory infiltrates suprapubic region
their collecting system IATROGENIC CYSTITIS (3) dysuria (pain or burning on urination)
-most common etiologic agents of -receiving systemic chemotherapy or pelvic irradiation
cystitis are the coliforms: Escherichia HEMORRHAGIC CYSTITIS INTERSTITIAL CYSTITIS(CHRONIC PELVIC PAIN SYNDROME)
coli, followed by Proteus, Klebsiella, -Cytotoxic agents, such as cyclophosphamide -an unpleasant sensation (pain, pressure, discomfort) perceived to be
and Enterobacter RADIATION CYSTITIS related to the urinary bladder, associated with urinary tract symptoms
-Women are more likely to develop -following the irradiation of the bladder region of more than six weeks duration, in the absence of infection or other
cystitis as a result of their shorter FOLLICULAR CYSTITIS identifiable causes
urethras -characterized by the presence of lymphoid follicles within the bladder mucosa and underlying -intermittent, often severe, suprapubic pain; urinary frequency; urgency;
-.Tuberculous cystitis is almost always wall hematuria; and dysuria
a sequel to renal tuberculosis EOSINOPHILIC CYSTITIS -mucosal fissures and punctate
-Gas-forming bacteria (such as -infiltration of the submucosa by eosinophils hemorrhages (glomerulations)
Clostridium perfringens) result in -mast cells are often increased in the submucosa
emphysematous cystitis (gas-filled MALAKOPLAKIA - Some cases are associated with chronic mucosal ulcers (Hunner
vesicles in the bladder wall). -soft yellow, slightly raised mucosal plaques, 3 to 4 cm in diameter ulcers); this is termed the late (classic, ulcerative) phase
2
, -aggregates of large foamy macrophages with occasional multinucleate giant cells and -transmural fibrosis may lead to a contracted bladder
lymphocytes
-macrophages have abundant granular cytoplasm MALAKOPLAKIA
-aminated mineralized concretions resulting from deposition of calcium in enlarged lysosomes, - distinctive chronic inflammatory reaction that appears to stem from
known as Michaelis-Gutmann bodies acquired defects in phagocyte function
-chronic bacterial infection, mostly by E. coli or occasionally Proteus
species, and occurs with increased frequency in the setting of
immunosuppression
POLYPOID CYSTITIS
-inflammatory lesion resulting from irritation of the bladder mucosa,
most commonly as a result of instrumentation
-urothelium is thrown into broad bulbous polypoid projections as a
result of marked submucosal edema
METAPLASTIC LESIONS CYSTITIS GLANDULARIS AND CYSTITIS CYSTICA
-nests of urothelium (von Brunn nests) grow downward into the lamina propria
-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)
-glandularis goblet cells are present, and the epithelium resembles intestinal mucosa (intestinal or colonic metaplasia)
SQUAMOUS METAPLASIA
-a response to chronic injury, the
urothelium is often replaced by nonkeratinizing or keratinizing squamous epithelium
-classic example Is seen with bladder schistosomiasis
NEPHROGENIC ADENOMA
-may not be a form of true metaplasia
-at least some of these lesions are caused by implantation and growth of renal tubular cells at sites of bladder mucosa erosion
-overlying urothelium is focally replaced by cuboidal epithelium, which can assume a papillary growth pattern
NEOPLASMS UROTHELIAL NEOPLASMS -Non– muscle-invasive papillary cancers often -Papillary lesions are red, elevated -Painless hematuria is the most -subsequent treatment and
- most common type have gain-of-function alterations that increase excrescences ranging in size from less common symptom course of bladder
-two distinct precursor lesions to signaling through growth factor receptor than 1 cm in diameter to large masses up -Frequency, urgency, and dysuria carcinoma depend on
invasive urothelial carcinoma: pathways, such as amplifications of the FGFR3 to 5 cm in diameter tumor grade and stage
noninvasive papillary tumors and flat tyrosine kinase receptor gene and activating -(non-invasive) small,
noninvasive urothelial carcinoma in mutations in the genes encoding RAS and PI 3- PAPILLOMAS localized low-grade
situ (CIS) kinase -often seen in younger patients papillary tumors, diagnostic
-most common precursor lesions are -majority of muscle-invasive bladder cancers -arise singly as small (0.5 to 2 cm), delicate transurethral resection
the noninvasive papillary tumors, develop by progression from “flat” CIS (mutations structures superficially attached to the -CIS and papillary tumors
which originate from papillary that disrupt the function of p53 and RB) mucosa by a stalk (exophytic papillomas) that are large, high grade,
urothelial hyperplasia -recurrently mutated genes involved in cell cycle -individual finger-like papillae have a multifocal, have a history of
-CIS is a term used to describe regulation, chromatin regulation, DNA repair, and central core of loose fibrovascular tissue recurrence, or are
epithelial lesions that have the growth factor signaling pathways covered by epithelium associated with lamina
cytologic features of malignancy but - -inverted papillomas are completely propria invasion are treated
are confined to the epithelium, benign lesions consisting of inter- with intravesical instillation
showing no evidence of basement anastomosing cords of cytologically of an attenuated strain of
membrane invasion (HIGH GRADE) bland urothelium that extend down into Mycobacterium bovis
-Although invasion into the lamina the lamina propria called bacillus Calmette-
propria worsens the prognosis, the Guérin (BCG)
3
