Lower Urinary Tract

The lower urinary tract extends from the kidney pelvis through the ureters, emptying into the urinary bladder, with final excretion through the urethra. Most toxicologic pathology lesions involve the mucosa, the distinctive urothelium. Toxicity usually occurs through urinary exposure rather than systemically. Any urothelial damage leads to regenerative proliferation. Ulceration leads to hemorrhage, acute inflammation, and granulation tissue. Proliferative lesions of the bladder range from simple to nodular and/or papillary hyperplasia and diffuse papillomatosis, which are reversible. Most lower urinary tract neoplasms are epithelial, primarily urothelial (transitional cell) papilloma and carcinoma, with occasional squamous cell carcinoma and others. Mesenchymal tumors are uncommon. Methods have been established for identifying histopathologic changes, superficial cytotoxicity, and increased proliferation, and sensitive methods are available for examination of urine. Uroplakins serve as a specific urothelial marker identifiable by immunohistochemistry. Modes of action and relevance to humans can be systematically investigated.