REVISION

1. REVISION 1. Name two causes of primary Addison’s disease. • What adrenal derivative is responsible for Cushing’s syndrome? • State a key difference, in relation to its pathophysiology, between Diabetes Mellitus Type I and Diabetes Mellitus Type 2. • Explain how hyperthyroidism (Grave’s disease) occurs in the body. • Identify 3 pathophysiologic changes in Hyperthyroidism. • List 4 causes of Hypothyroidism. • What endocrine disorder is fluid retention most commonly associated?

2. ALTERATIONS TO THE REPRODUCTIVE SYSTEM

3. Pathophysiologic Concepts Hormonal Alterations: Defect or malfunction of the hypothalamic-pituitary-ovarian axis system (in females). May cause infertility due to insufficient gonadotropin secretions (both LH and FSH). Possible causes of insufficient gonadotropin levels: infections, tumours, neurologic disease of hypothalamus or pituitary gland. Ovarian control related to systems of negative and positive feedback mediated by oestrogen production. Sporadic inhibition of ovulation related to hormonal imbalance in gonadotropin production and regulation, or abnormalities in adrenal or thyroid gland that adversely affect HP functioning. Male hypogonadism results from decreased androgen production: May impair spermatogenesis, causing infertility May inhibit development of normal secondary sex characteristics.

4. Pathophysiologic Concepts Male Structural Alterations: Structural defects may be acquired or congenital Benign prostatic hyperplasia involves prostate enlargement due to androgen-induced growth of prostate cells; may result in urinary obstructive symptoms. Menstrual Alterations: Menopause marks cessation of ovarian function: results from complex continuum of physiologic changes caused by normal, gradual decline of ovarian function. Most dramatic climacteric change: cessation of menses. Premature menopause occurs without apparent cause; affects about 5 percent of women in Australia. Artificial menopause may follow radiation therapy or surgical procedures such as bilateral oophorectomy. Ovarian failure may result from function ovarian disorder caused by premature menopause; amenorrhoea ensues.

5. Benign Prostatic Hyperplasia Characterised by enlargement of the prostate gland and compression of the urethra, causing overt urinary obstruction. Typically associated with aging Treated symptomatically or surgically, depending on prostate size, age and health of patient, and extent of obstruction. Pathophysiology: Regardless of the cause, BPH begins with non-malignant changes in peri-urethral glandular tissue. The growth of the fibroadenomatous nodules progresses to compress the remaining normal gland. As the prostate enlarges it may extend into the bladder and obstruct urinary outflow by compressing or distorting the prostatic urethra.

6. Benign Prostatic Hyperplasia Causes: Exact cause unknown Possible age-related changes in hormone activity: androgenic production decreases with age, causing imbalances in androgen and oestrogen levels and high levels of dihydrotestosterone. Risk Factors: Aging Family History Pathophysiologic Changes: Enlarged prostate: reduced urinary stream calibre and force; urinary hesitancy; difficulty starting micturition Increased Obstruction: Frequent urination with nocturia; dribbling; urine retention; incontinence; sense of urgency; possible haematuria.

7. Breast Cancer Most common cancer affecting women May develop any time after puberty; most common after age 50. Pathophysiology: Breast cancer is more common in the left breast than in the right and more common in the upper outer quadrant. Growth rates vary. It spreads by way of the lymphatic system and bloodstream to the other breast, the chest wall, liver, bone and brain. Classified by histologic appearance and the lesions location: adenocarcinoma: arising from the epithelium Intra-ductal Infiltrating Inflammatory Lobular carcinoma in-situ Medullary or circumscribed

8. Breast Cancer Causes: Unknown, but its high incidence in women implicates oestrogen Possible causes: oestrogen therapy, anti-hypertensive agents, high-fat diet, obesity, fibrocystic breast disease. Risk factors: Factors associated with high risk: Family History Genetic mutations in BRCA-1 and BRCA-2 genes Long menses No history of pregnancy First pregnancy after age 30 History of unilateral breast cancer Exposure to low level ionizing radiation

9. Breast Cancer Risk Factors Factors associated with a low risk: History of pregnancy before age 20 Pathophysiologic Changes: Mutation of cells in breast tissue: Lump or mass in breast; change in breast size or symmetry; change in nipple and nipple discharge. Fixation of cancer to pectoral muscle and underlying fascia. Oedema Advanced spread within breast Metastasis

10. Endometriosis Presence of endometrial tissue outside lining of uterine cavity (ectopic tissue). Generally confined to pelvic area (usually around ovaries, utero-vesical peritoneum, utero-sacral ligaments), but can occur anywhere in the body. Classical symptoms: dysmenorrhoea, abnormal uterine bleeding and infertility. Pathophysiology: Ectopic endometrial tissue can implant almost anywhere in the peritoneum. It responds to normal stimulation in the same way as the endometrium, but more unpredictably. The endometrial cells respond to oestrogen and progesterone with proliferation and secretion. During menstruation, the ectopic tissue bleeds, which causes inflammation of the surrounding tissues. This inflammation causes fibrosis, leading to adhesions that produce pain and infertility.

11. Endometriosis Causes: Exact cause unknown May be related to: Retrograde menstruation with endometrial implantation at ectopic sites. Genetic predisposition and depressed immune system Coelomic metaplasia Extra-peritoneal disease Pathophysiologic Changes: Implantation of ectopic tissue and adhesion Ectopic tissue in ovaries and oviducts Ectopic tissues in ovaries or cul-de-sac Ectopic tissue in bladder Ectopic tissue in large bowel and appendix Ectopic tissue in cervix, vagina and peritoneum

12. Herpes Simplex Type 2 Recurrent viral infection caused by Herpes virus hominis Also known as genital herpes Primarily affects genital area; commonly transmitted by sexual contact. Cross-infection may result from oro-genital sex. Characterised by painful, fluid-filled vesicles that appear in genital area. Treatment is largely supportive; no known cure. Pathophysiology: Herpes simplex Type 2 is transmitted by contact with infectious lesions or secretions. The virus enters the skin, local replication of the virus occurs, and the virus enters cutaneous neurons. After the patient becomes infected, a latency period follows, although repeated outbreaks may develop at any time.

13. Herpes Simplex Type 2 Initial infection Latency Recurrent Infection

14. Herpes Simplex Type 2 Causes: Transmission of Herpes virus hominis Primarily by sexual contact Possibly by auto-inoculation with type with Type 1 Pregnancy related transmission Pathophysiologic Changes: Viral penetration of skin, viral replication, and entry into cutaneous neurons Painful lesions Progression of viral infection

15. Prostate Cancer Slow growing, most common neoplasm in men over age 50. Commonly forms adenocarcinoma; sarcoma rarely develops. Usually originates in posterior prostate gland; sometimes originates near urethra. Seldom results from benign hyperplastic enlargement. Clinical manifestations typically associated with latter stage disease. Pathophysiology: Prostate cancer grows slowly. When primary lesions metastasize beyond the prostate, they invade the prostate capsule and spread along the ejaculatory ducts in the space between the seminal vesicles. Causes: Exact cause unknown Predisposing factors: aging and genetic component Ethnic origin Exposure to environmental and occupation toxins

16. Prostate Cancer Pathophysiologic Changes: Obstruction of urinary tract by tumour Infiltration of bladder by tumour Bone metastasis Management: Radiation therapy Radioactive seed implants into prostate Radical Prostatectomy Transurethral resection of prostate Orchiectomy

17. Toxic Shock Syndrome Acute bacterial infection caused by toxic-producing, penicillin-resistant strains of Staphylococcus aureus. Primary affects menstruating women under age 30 Associated with continuous use of tampons during menstrual period Pathophysiology: Is an acute bacterial infection caused by toxin-producing penicillin-resistant strains of staphylococcus aureus. Toxin producing bacterial pathogens are introduced into the vagina by way of contaminated fingers or tampon applicator, and the menstrual flow provides a medium for bacterial growth.

18. Toxic Shock Syndrome Causes: Tampon-related mechanism Infection of S. aureus unrelated to menstruation: Abscess Osteomyelitis Post-surgical infections Use of contraceptive devices Recent childbirth Pathophysiologic Changes: Toxin producing infection Hypersensitivity reaction to toxin Disease progression

19. Vulvovaginitis Inflammation of the vulva and vaginal mucosa, resulting from bacterial or viral infection, vaginal atrophy, or various traumas or irritants. Signs and Symptoms: Vaginal discharge Possible vulvar irritation, pain or pruritus

20. Cervical Cancer Pre-invasive cancer causes minimal cervical dysplasia in lower third of epithelium; invasive cancer penetrates basement membrane to disseminate throughout body via lymphatic route. Signs and Symptoms: Abnormal vaginal bleeding, persistent vaginal discharge. Post-coital pain and bleeding Pelvic pain; Vaginal leakage of urine or faeces due to fistula. Anorexia, weight loss and anaemia

21. Cervical Cancer Pathophysiology: The pathogenesis of cervical cancer has been linked to HPV infection. HPV 16 accounts for almost 60 percent of cervical cancer cases. Marked by Metaplasia and Squamous cell carcinoma Other Factors: Cigarette smoking Dietary and Nutritional Factors Early age of first sexual intercourse Family history of cervical cancer HIV infection Use of oral contraceptives

22. Vaginitis Vaginitis represents an inflammation of the vagina that is characterised by vaginal discharge and burning, itching, redness and swelling of vaginal tissue. Pain often occurs with urination and sexual intercourse. Pathophysiology: Vaginitis differs in various age groups. In pre-menarchal girls, most vaginal infections have non-specific causes such as poor hygiene, intestinal parasites, or the presence of foreign bodies. Candida albicans, Trichomonas vaginalisand bacterial vaginosis. Decrease in oestrogen.

23. Pelvic Inflammatory Disease Poly-microbial infection of the upper reproductive tract. Associated with sexual transmitted organisms and endogenous organisms. Pathophysiology: The organisms ascend through the endo-cervical cavity, and then to the fallopian tubes and ovaries. The endo-cervical canal is slightly dilated during menstruation, allowing bacteria to gain entrance to the uterus and other pelvic structures. After entering the upper reproductive tract, the organisms multiple rapidly and eventually ascend to the fallopian tubes. Risk Factors: History of multiple sexual partners Nulliparity Previous history of PID Use of an IUD

24. Pelvic Inflammatory Disease Symptoms: Abdominal pain Dyspareunia Back pain Cervical Discharge Abdominal tenderness Break-through bleeding

25. Polycystic Ovary Syndrome Common endocrine disorder affecting 5 to 10 percent of women of reproductive age. Disorder is characterised by varying degrees of menstrual irregularity, signs of hyperandrogenism and infertility, associated with hyper-insulinemia or insulin resistance. Pathophysiology: The underlying aetiology of the disorder is unknown, although most women have altered gonadotropin levels . Changes in hormone profiling.