Urothelium

  The urothelium is the tissue layer that lines much of the urinary tract, including the renal pelvis, the ureters, the bladder, and parts of the urethra.

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Functions

Urothelium is the most specialized epithelium and plays important and conflicting roles: the urothelium must act as a permeability barrier -- protecting underlying tissues against noxious urine components — while also stretching to accommodate urine pressures.

Structure

Urothelium is a tissue layer of approximately 3-5 cell layers, accompanied by a thick layer of protective glycoprotein plaques at its luminal (apical) surface, and is classified as transitional epithelium. Epithelia are tissue layers that line interior and exterior body surfaces:

• skin
• mucosal linings of the mouth/lung/digestive and reproductive tracts
• lining of ducts in prostate and breast

Multi-layered epithelia are typically structured with specialized, mature cells at the surface, whereas less mature "basal" cells are the least mature cell layer at the base of the epithelium. The mature surface cells are continually sloughed off and are replaced by a supply of newly maturing cells. The basal cell layer contains tissue-specific stem cells that are capable of cell division for the lifetime of the animal and thereby generate the pool of maturing cells that maintains tissue homeostasis. Because of this continual epithelial renewal process, chemotherapeutic drugs that interfere with cell division can cause complications of deteriorating epithelia (e.g., oral sores).

Pathology

Epithelia are sites of specific diseases.

• Cancers that originate in epithelial cells are termed carcinomas, and they are characterized as having lost the mature, differentiated morphology and molecular patterns of the normal tissue. Infectious diseases also afflict epithelia where diverse microbes (viruses, bacteria, fungi) have surface structures that bind specific features of particular epithelial cells (e.g., influenza virus binds repiratory epithelium). Genetic defects can also inhibit normal epithelial integrity, such as defects in intercellular adhesion molecules that result in blistering diseases.

• The second most common infectious disease is urinary tract infection (UTI). UTIs afflict approximately half of all women during their lifetime, and about 25% of these women will suffer recurrent UTIs. The majority of these infections are due to uropathogenic Escherichia coli bacteria (commonly known as E. coli). However, UTIs can also develop in healthcare settings and such infections are caused by a greater frequency of non-E. coli bacteria.

• One unusual condition which affects the urothelium is interstitial cystitis (IC), a condition with symptoms similar to UTI (frequency, urgency, pressure and/or pain). Urine culture, however, is negative. During hydrodistention of the bladder, small petechial hemorrhages (aka glomerulations) are frequently found throughout the bladder. Larger "Hunner's Ulcers", known for their characteristic waterfall bleeding effect, represent larger areas of bladder wall thinning and/or trauma. The cause of IC is currently unknown though some suggest that it could be genetic, the result of traumatic injury (aka chemical exposure), infection, autoimmune disease, etc. Researcher Susan Keay (University of Maryland) has found an unusual protein in the urine of IC patients which appears to interfer with healing, known as an Antiproliferative Factor. Research efforts into IC are focused on the urothelium, including newly discovered signaling molecules which suggest that the urothelium is far more than a barrier, as well as how the urothelium interacts with proximal nerves and smooth muscle.

• Urothelium is susceptible to carcinoma. Because the bladder is in contact with urine for extended periods, chemicals that become concentrated in the urine can cause Bladder cancer. For example, cigarette smoking leads to the concentration of carcinogens in the urine and is a leading cause of bladder cancer. Occupational exposure to certain chemicals is also a risk factor for bladder cancer.