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D’YOUVILLE COLLEGE PMD 604 - ANATOMY, PHYSIOLOGY, PATHOLOGY II Lecture 12: Reproductive Disorders Robbins chapters 18 & 19 1. Male Reproductive Disorders: • disorders of penis: - hypospadias & epispadias: abnormal formations of urethra in which external opening is on ventral (hypospadia) or dorsal (epispadia) surface of penis; rare disorders (usually congenital) that may cause obstruction or urinary incontinence; surgical correction - inflammations: glans & prepuce are usual sites - may be attributable to poor hygiene (mostly in uncircumcised individuals); materials accumulated under prepuce (smegma) may contain irritants or infective agents that provoke inflammation - sexually transmitted diseases (STDs) are usual sources of infections -tumors: squamous cell carcinomas are most frequent type; most often associated with human papilloma virus (HPV) infection • testicular disorders: - cryptorchidism (failure of testicular descent) (ppt. 1) is a congenital defect that results in atrophy of seminiferous tubules (ppt. 2); if condition is unilateral, fertility may be retained; bilateral cryptorchidism or accompanying contralateral atrophy results in sterility - testosterone production is normal - an undescended testis is more vulnerable to tumor development - inflammations may result from genitourinary infections (e.g. STDs); chronic inflammations may involve autoimmune lesions (e.g. following tuberculosis) - testicular tumors: majority develop from spermatogenic tissue (germ cells) - tumors that retain spermatogenic cell characteristics (seminomas) are less likely to metastasize & are sensitive to radiation so cure rates are high - nonseminomatous tumors involve neoplasias that express more totipotent characteristics (e.g. trophoblastic traits, yolk sac traits, or undifferentiated traits); tumor markers that may be detected include hCG (trophoblastic product) and fetoprotein (yolk sac product) metastases spread to epididymis, pelvic lymph nodes, urethra & bladder, and lungs; PMD 604 lec 12 - p. 2 - • prostate disorders: - prostatitis: bacterial (acute) or fungal (chronic) infection - benign prostatic hypertrophy (BPH): normal increase in size (hyperplasia, not hypertrophy) after age 45, increases frequency with age; more appropriately known as nodular hyperplasia; nodular characteristics vary according to regional distribution of hyperplastic growth (fig. 18 - 10 & ppt. 3) - may contribute to urinary obstruction in more severe cases (fig. 18 - 11 & ppt. 4) - increased risk of bladder infection or pyelonephritis due to urine retention - prostatic carcinoma: no evidence that tumor development is linked to BPH - tumors are often smaller & peripheral, so little urinary obstruction occurs and tumors can progress substantially before detection (fig. 18 - 13 & ppt. 5) - advanced neoplasms have increased risk of metastasis - detected by testing for elevation of prostate specific antigen (PSA) 2. Female Reproductive Disorders: • pelvic inflammatory disease: vaginal infections, e.g., from sexually transmitted diseases (STDs), may pass into uterus, uterine tubes, ovaries and other points in peritoneal cavity; purulent exudate results & may be expelled via vagina or produce abscesses more internally - sexual promiscuity increases risk as does such interventions as C-section surgery, D & C surgery and even high frequency of vaginal douching - scarring from inflammatory response may produce adhesions, strictures of uterine tubes, tubal and/or ovarian abscesses; scarring (evident in endoscopic exam) is diagnostic - likely loss of fertility - predisposes patient to such conditions as endometriosis, ectopic pregnancy or ovarian tumors • uterine disorders: usually involve lining (endometrium), cervical epithelium or muscular wall (myometrium); often accompanied by uterine bleeding - cervical carcinoma follows a standard progression involving dysplasia in transformational zone (fig. 19 - 5 & ppt. 6); these growths are termed cervical intraepithelial neoplasias (CINs) and some more severe growths may develop into cancer (fig. 19 - 6 & ppt. 7) - most often related to exposure of exocervix to human papilloma virus (HPV) infections, frequently as a result of sexual promiscuity - cancers are mostly squamous cell carcinomas or adenocarcinomas - metastasis via lymphatics, especially targets liver or lungs - PAP smear usually detects growth changes before carcinoma develops (fig. 19 - 8 & ppt. 8) & has substantially reduced incidence of squamous cell carcinomas PMD 604 lec 12 - p. 3 - - endometriosis is a condition involving bits of endometrium that become established at extrauterine sites (mostly ovaries, but also lymphatics or distant sites) - may spread via vascular or lymphatic embolization, regurgitation of menses through uterine tube or metaplasia of peritoneum (fig. 19 - 10 & ppt. 9) - the tissue cycles like the intrauterine endometrium (proliferation, secretion, necrosis & bleeding) with associated pain, cramping & dysmenorrhea PMD 604 lec 12 - p. 4 - - endometrial carcinoma may be caused by excessive levels of estrogen (endometrioid carcinoma) or a genetic mutation (serous carcinoma) - may invade myometrium, metastasize to ovaries or lungs - usual treatment is hysterectomy • ovarian disorders: - ovarian cysts may develop from graafian follicles - polycystic ovarian syndrome (PCO): enzyme defect causes excessive androgen production, resulting in hirsutism - conversion of androgens to estrogens in adipose generates a feedback that disrupts normal hypothalamo-hypophysial-gonad axis function, resulting in anovulation with development of multiple cysts & infertility (ppt. 10) - ovarian tumors: malignancies are particularly dangerous since detection is unlikely to precede metastasis - tumors may arise via transformation of various ovarian cell types (fig. 19 - 16 & ppt. 11) - tumors of germ cell tissue are mostly benign; epithelial tumors are more often malignant and may resemble endometrium (endometrioid adenocarcinoma) • disorders of pregnancy: - ectopic pregnancy: implantation occurs at a site other than the intrauterine endometrium (mostly in uterine tube) - may develop with endometriosis or with obstructed uterine tube as a sequel of pelvic inflammatory disease - embryonic growth may burst uterine tube causing hemorrhage and circulatory shock, but many cases lead to spontaneous degeneration & resorption (approximately 40% of all pregnancies end in spontaneous abortion for various genetic &/or congenital reasons) - gestational tumor: two main growths, both associated with elevated hCG - the invasive mole, which doesn't metastasize, but may perforate uterine wall; associated with chromosomal aberration involving extra paternal chromosomes - the highly malignant choriocarcinoma, which may be associated with normal or unsuccessful pregnancies; metastasizes early & widely - preeclampsia/eclampsia: pregnancy-induced hypertension, accompanied by loss of albumin in urine (albuminuria) and systemic edema (preeclampsia) - placental ischemia & infarction due to abnormal placental blood flow may cause emergence of seizures (eclampsia) (ppt. 12) • breast cancer: - two types of neoplasia include carcinoma in situ (CIS), which is noninvasive, but may transform to invasive carcinoma - the first develops in ducts and glandular tissue, while the invasive type spreads to stroma and lymphatics and can metastasize; metastasis may be delayed for years - treatment involves surgical removal (lumpectomy or mastectomy) often followed by tamoxifen, a drug that blocks estrogen support of tumor growth PMD 604 lec 12 - p. 5 - - TNM grading system is widely used to determine treatment options (ppt. 13)