Lower Urinary Tract and Male Genital System

What structures make up the lower urinary tract (LUT)?

Renal pelvis

Ureters

Bladder

Urethra

What specialized epithelium lines the lower urinary tract?

Urothelium — A specialized form of transitional epithelium

What are the three major layers of the urinary tract wall?

1. Urothelium

2. Lamina propria

3. Muscularis propria

What structures are found within the lamina propria of the urinary tract?

Rich vascular and lymphatic networks

Elastic fibers

Smooth muscle fibers (muscularis mucosae)

Sensory nerves

Other cells

What is the muscularis propria of the bladder called?

Detrusor muscle

What type of muscle forms the external urethral sphincter?

Skeletal muscle

What structure is this showing?

Ureter

What structure is this showing?

Bladder

What are the three major cell groups of urothelium?

Umbrella cells — superficial

Intermediate cells

Basal cells

(Cells are DISTINCT morphologically and genetically)

What are the two major functions of urothelium?

Allows the urinary tract to distend

Provides a highly effective barrier against urine and pathogens

What is unique about the permeability of urothelium?

Forms the MOST impermeable barrier in the body

How many cell layers are typically present in urothelium?

Approx. 2-7 layers

• Depends on the degree of distention

What are umbrella cells?

Large, flattened, with abundant cytoplasm

Terminally differentiated superficial urothelial cells that directly face the urinary lumen

What structures are primarily responsible for the barrier function of umbrella cells?

Tight junctions

Adherens junction

What is the primary function of intermediate urothelial cells?

Highly proliferative

Responsible for rapid regeneration following injury or infection

How are intermediate cells connected to one another?

Primarily through desmosomes

How do intermediate cells look histologically?

Approx. 5 layers in human

Larger in diameter than basal cells

What are basal urothelial cells?

The smallest urothelial cells

• Approximately 5–10 μm

Sit directly on the basement membrane

What junctions attach basal cells to the basement membrane?

Hemidesmosomes

What junctions attach basal cells to intermediate cells?

Desmosomes

Which urothelial cell population may contain stem cells responsible for lifelong regeneration?

Basal cells

What is this?

Basement membrane

Lamina propria

What is a ureteropelvic junction (UPJ) obstruction?

A blockage where the renal pelvis connects to the ureter

• Impair urine flow and causing urine to back up into the kidney

What is the major consequence of UPJ obstruction?

Hydronephrosis due to impaired urine drainage

What is the most common cause of hydronephrosis in infants and children?

Ureteropelvic junction (UPJ) obstruction

What is the approximate incidence and sex distribution of UPJ obstruction?

Approx. 1 in 1,500 births

• Boys > Girls

How does UPJ obstruction differ epidemiologically in adults?

More common in women

Usually unilateral

What is the treatment for UPJ obstruction?

Pyeloplasty (surgical correction)

• A surgical operation used to fix a blocked or narrowed tube where your kidney meets your ureter

What is retroperitoneal fibrosis (RPF)?

A fibroinflammatory process that produces fibrous tissue around retroperitoneal structures

• Can encase and obstruct the ureters

(Uncommon cause of ureteral narrowing or obstruction)

What urinary complication can result from retroperitoneal fibrosis?

Fibrotic inflammation → encases retroperitoneal structures → hydronephrosis

• The swelling of one or both kidneys caused by a backup of urine

What demographic is most commonly affected by RPF?

Adults approximately 40–60 years old

• A male predominance (2:1 or 3:1)

What is the most common cause/category of retroperitoneal fibrosis?

Idiopathic disease (>70%), also called Ormond disease

What is an important immune-mediated form of retroperitoneal fibrosis?

IgG4-related disease

• Characterized by fibroinflammatory lesions rich in IgG4-secreting plasma cells

What other conditions can be associated with retroperitoneal fibrosis?

Malignancies

Vasculitis

Crohn disease

Radiation

Infections

Prior surgery

Certain drugs such as β-adrenergic blockers

How is retroperitoneal fibrosis treated?

Corticosteroids/immunosuppression

Ureteral stents

Surgery

What is a bladder diverticulum?

A pouch-like evagination of the bladder wall

Most are small and asymptomatic

What can cause congenital bladder diverticula?

Abnormal development of bladder musculature or LUT obstruction during fetal development

What is the most common association with acquired bladder diverticula?

Urinary outflow obstruction due to BPH

• Increases intravesical pressure

What complications can occur in bladder diverticula?

Urinary stasis → Recurrent UTIs and bladder stones

What is this X-ray showing?

Bladder diverticulum

What is this?

Bladder diverticulum

What is this showing histologically?

Bladder diverticulum

What is cystitis?

Inflammation of the urinary bladder

What are the classic symptoms of cystitis?

Urinary frequency

Lower abdominal pain

Dysuria

What is the most common cause of bacterial cystitis?

E. coli

• More COMMON in women due to shorter urethra

What complication can result from untreated bacterial cystitis?

Pyelonephritis due to ascending infection

• A serious type of urinary tract infection (UTI) that travels to one or both of your kidneys

What causes hemorrhagic cystitis?

Cytotoxic drugs — Cyclophosphamide and

Certain viral infections

• Particularly adenovirus

What is interstitial cystitis?

A chronic pelvic pain syndrome of unknown etiology

• Most frequently occurring in women

What are characteristic cystoscopic findings in interstitial cystitis?

Mucosal fissures

Punctate hemorrhages

What is the major role of pathology in interstitial cystitis?

Histologic findings are nonspecific

Biopsy is primarily useful to rule out carcinoma in situ (CIS)

What is malakoplakia?

A rare form of chronic cystitis

• Associated with defective macrophage phagocytic function

What are Michaelis-Gutmann bodies?

Calcium-containing deposits

• Formed from incompletely digested bacterial products within macrophages

What is the pathogenesis of malakoplakia?

Defective macrophage phagocytosis → Accumulation of undigested bacterial products in phagosomes → Calcium salt deposition → Michaelis-Gutmann bodies

What is this?

Hemorrhagic cystitis

What is the most common type of bladder cancer in the United States?

Urothelial carcinoma

• Approximately 90% of bladder cancers

What is the approximate male-to-female ratio for bladder cancer?

Approximately 3:1

• Men affected more frequently

What is the classic clinical presentation of bladder cancer?

Asymptomatic hematuria

What population demographic is more commonly associated with bladder cancer?

Higher incidence in Caucasians

More prevalent in industrialized nations, and in urban populations

About 80% of patients are between 50 and 80 years of age

What are major risk factors for urothelial carcinoma?

Cigarette smoking

Occupational carcinogen exposure

Previous cyclophosphamide and radiation therapy

What is a major risk factor for squamous cell carcinoma of the bladder that causes chronic inflammation?

Chronic Schistosoma haematobium infection

What geographic location is Schistosoma haematobium particularly associated with bladder SCC?

Endemic regions including Egypt and Sudan

Why does schistosomiasis increase the risk of bladder SCC?

Chronic inflammation

• Associated with the infection promotes malignant transformation

What are the two distinct precursor lesions of bladder cancer?

Papilloma → Invasive papillary carcinoma

Flat noninvasive carcinoma (CIS) → Flat invasive carcinoma

What are the two molecular pathways of bladder cancer?

RAS, FGFR3 mutation → Papillary urothelial neoplasm → P53 mutation (additional genetic mutations) → Invasive papillary carcinoma

TP53. RB mutation → Flat noninvasive carcinoma (CIS) → Chr 9 loss (additional genetic mutations) → Flat invasive carcinoma

What is this?

Papilloma

What is this?

Papilloma

What are the major papillary urothelial neoplasms listed in the lecture?

Papilloma

PUNLMP

Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma

What is this histologically showing?

Papilloma

PUNLMP (Papillary urothelial neoplasm of low malignant potential)

Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma

What is the most important prognostic factor for papilloma?

Grade

• Based on architectural and cytologic features

Which papillary urothelial neoplasm has the lowest malignant potential?

Papilloma

What does PUNLMP stand for?

Papillary urothelial neoplasm of low malignant potential

What is urothelial carcinoma in situ (CIS)?

A flat malignant urothelial lesion in which malignant cells are confined above the basement membrane without invasion

Can “flake off” into the luminal space

What characteristic of urothelial CIS allows malignant cells to be detected in urine cytology?

Loss of cellular cohesiveness causes malignant cells to shed into the urine

Is urothelial CIS typically solitary or multifocal?

Multifocal

What percentage of untreated urothelial CIS progresses to invasive cancer?

Approx. 50-75%

How is urothelial CIS commonly treated?

BGC (immunotherapy) treatment

What is this?

Invasive urothelial carcinoma

What is this showing histologically?

Invasive urothelial carcinoma

What is the most important prognostic factor once urothelial carcinoma becomes invasive?

Extent/stage of invasion at the time of diagnosis

Where can urothelial carcinoma arise?

Anywhere lined by urothelium, including the:

• Bladder

• Ureter

• Renal pelvis

What is a characteristic behavior of bladder urothelial carcinoma after excision?

A strong tendency to recur

Recurrence may occur at a site different from the original tumor

How do low-grade and high-grade urothelial carcinomas differ in behavior?

Low grade: Recur but NO invasion

High grade: Concurrent or subsequent invasion

What is the typical treatment for localized papillary bladder tumors?

Transurethral resection

How are CIS and high-grade papillary bladder tumors commonly treated?

BCG immunotherapy ± intravesical chemotherapy

What treatment is generally used for muscle-invasive bladder carcinoma?

Radical cystectomy

• Also useful for BCG resistant CIS/HGUC

Cystoprostatectomy

Radiation and/or chemotherapy as appropriate

What treatment is generally used for metastatic bladder carcinoma?

Systemic chemotherapy

Understand penis anatomy

What is hypospadias?

An abnormally positioned urethral opening on the ventral surface of the penis

• Common, 1 in 300 male live births

Where are penis malformations most common?

In the distal urethral orifice

What embryologic defect causes hypospadias?

Failure of the urethral folds to close

What congenital anomaly is associated with hypospadias?

Undescended testis (cryptorchidism)

What complications can hypospadias cause?

Urinary obstruction

Infertility

What is epispadias?

An abnormally positioned urethral opening on the dorsal surface of the penis

Less common penis malformation

What embryologic abnormality causes epispadias?

Abnormal positioning of the genital tubercle

What congenital condition is strongly associated with epispadias?

Bladder exstrophy

• A rare birth defect where the bladder develops outside the fetus's abdomen and is turned inside out

What is balanitis?

Inflammation of the glans penis

What is balanoposthitis?

Inflammation involving the prepuce (foreskin) and glands

What organisms can cause balanitis/balanoposthitis?

Fungal (Candida)

Anaerobic bacteria

Gardnerella

What is smegma?

Accumulated desquamated epithelial material associated with poor hygiene

• Particularly in uncircumcised males

What is phimosis?

Inability to easily retract the prepuce