Ch. 32, 33, 34 Module 12 - patho

Which hormone stimulates the secretion of FSH?

Activin

Compare and contrast benign prostatic hypertrophy, prostatitis, and prostate cancer.

Benign prostatic hyperplasia (BPH) is the most common disorder of the male reproductive system. Its etiology is believed to be related to alterations in endocrine (androgens, estrogens, gonadotropins, and prolactin) and growth factor (e.g., insulin-like growth factor) activity. Aging-related processes such as prostatic hypoxia and bladder dysfunction may also play a role. in the periurethral glands at around 40 years of age, hyperplasia of prostatic tissue leads to the formation of nodules that compress the urethra. Over time, this process can progress from mild reductions in the force of urinary stream and delay in starting urination to inadequate bladder emptying with overflow incontinence to urethral obstruction and hydronephrosis. Prostatitis is inflammation of the prostate that occurs when structural malformations or instrumentation weaken the natural defense mechanisms. In acute bacterial prostatitis, bacteria such as Escherichia coli, Enterococcus, Klebsiella, or Chlamydia trachomatis ascend the urethra and enter the prostate, causing intense inflammation with edema of the prostatic tissue and compression of the urethra. Risk factors include BPH, urethral instrumentation or catheterization, and decreased immune competence in the urinary tract. Symptoms are similar to those of an urinary tract infection or pyelonephritis and Fever (104° F), Dysuria, nocturia, Lower back and perineal pain, Urinary retention, narrowed urinary stream. Chronic bacterial prostatitis results from recurrent or persistent bacterial infection of the prostate. This disorder is frequently characterized by the presence of prostatic calculi that harbor bacteria and make eradication of the organisms very difficult. Chronic inflammation can lead to fibrotic changes in the gland. Sx include Dysuria, urgency, Perineal and low back discomfort, Sexual dysfunction, Slightly enlarged, boggy prostate. Asymptomatic inflammatory/chronic pelvic pain syndrome results from recurrent inflammation reflux of sterile urine into the ejaculatory ducts triggered by high pressure voiding. Symptoms are the same as for chronic bacterial prostatitis but generally are less severe: Dull pain in the perineal area, Urinary frequency, Pain on ejaculation Prostate cancer - During the aging process, testosterone metabolism in the prostate changes such that 5α reductase production of dihydroxytestosterone (or DHT) decreases, and production of estradiol increases. This causes an increase in the estrogen-to-androgen ratio in the prostate gland. This hormonal change, along with increases in insulin-like growth factor, genetic vulnerability, and environmental influences such as high-fat diet and vasectomy, combine to cause increases in toxic oxygen radicals, DNA mutation, and uncontrolled cellular growth. Cancer begins within the prostatic capsule but can progress with local extension into lymphatic and blood vessels, with subsequent metastasis to bone, lung, liver, adrenal glands, and serosa such as the pleura and peritoneum. often asymptomatic in its early stages, and metastasis to bone with resultant bone pain is a common reason for individuals to first seek care. If clinical manifestations develop, they may be caused by obstruction of the urethra. Decreased force of stream, Hesitancy, frequency, nocturia, Urinary retention, Constipation; may result from extension of the cancer into the rectum. Symptoms of advanced disease: Bone pain, Lower extremity edema, Enlarged lymph nodes, Hepatomegaly

What causes impaired spermatogenesis?

Defects in testicular response to the gonadotropins result in decreased secretion of testosterone and inhibin B and occur as a result of normal feedback mechanisms and high levels of circulating gonadotropins. In the absence of adequate testosterone levels, spermatogenesis is impaired. can be caused by testicular trauma, infection, atrophy of the testes, systemic illness involving high fever, ingestion of various drugs, exposure to environmental toxins, and cryptorchidism

Describe the clinical manifestations of premenstrual syndrome.

Depressive symptoms Irritability, anger Fatigue

A nurse recalls the _____ is lined with columnar epithelial cells.

Endocervical canal

The area of the penis with the most nerve endings

Glans

What are the risk factors for cancer of the penis?

HPV infection, smoking, low socioeconomic status, poor personal hygiene, and psoriasis (possibly autoimmune diseases linked to the lack of clearance of HPV)

What are the risk factors for male breast cancer?

Klinefelter syndrome is the strongest risk factor, Other risk factors include germline mutation in BRCA1 or BRCA2, but familial cases usually have BRCA2, Obesity increases the risk, Testicular disorders, including cryptorchidism, mumps, orchitis, and orchiectomy, are related

Which cells produce testosterone?

Leydig cells

Discuss the new hypothesis for pathogenesis of ovarian cancer.

Newer evidence suggest that tumors arise from three ovarian components: (1) from the fimbriae of fallopian tubes and from deposits of endometriosis; (2) from germ cells, which are pluripotent and migrate to the ovary from the yolk sac; and (3) from stromal cells, including the sex cords, which precede endocrine changes of the postnatal ovary a newer hypothesis is that the cysts arise from implantation of detached fallopian tube epithelium at sites where ovulation has disrupted the surface of the ovary.

Identify the basic features of polycystic ovary syndrome.

Oligo-ovulation or anovulation Elevated levels of androgens and clinical signs of hyperandrogenism Polycystic ovaries

Discuss the role of the microenvironment or stromal tissue on breast cancer development.

One hypothesis is that the stromal-rich environment in MBD may have an abundance of growth factors that could stimulate the epithelium in a noninvoluted breast, thereby increasing the risk of malignant transformation. Leptin secreted by adipocytes and fibroblasts in the microenvironment act on breast cancer cells in a paracrine fashion. the biology of specific subtypes reflects contributions from the microenvironment Multiple stromal cell types create a succession of tumor microenvironments that change as tumors invade normal tissue, eventually seeding and colonizing distant tissues. The organization, numbers, and phenotypic characteristics of the stromal cell types and the extracellular matrix (hatched background) evolve during progression and enable primary, invasive, and metastatic growth

Cells of the _____ have receptors for gonadotropins.

Ovary

Why is prompt treatment of pelvic inflammatory disease (PID) critical to reproductive health?

The acute complications of PID include peritonitis and bacteremia, which can increase the risk for endocarditis, meningitis, and infectious arthritis. The chronic consequences of PID include infertility and tubal obstruction, ectopic pregnancy, pelvic pain of varying degrees, and intestinal obstruction from adhesions between the bowel and pelvic organs

Name three functions of the uterus.

anchors and protects a fertilized ovum, provides an optimal environment while the ovum develops, and pushes the fetus out at birth. In addition, the uterus plays an important role in sexual response and conception

Why is cervical cancer considered a sexually transmitted infection?

because it is caused by HPV

Why do anovulatory cycles lead to dysfunctional uterine bleeding?

because of a lack of progesterone and, in some cases, an excess of estrogen. This results in excessive and irregular endometrial thickness and subsequent excessive and irregular bleeding

The glands of the Montgomery are located in the:

breasts

Why do all forms of precocious puberty require evaluation?

can be lethal central nervous system tumors or cause long bones to stop growing before the child has reached normal height.

What are the long-term health consequences for MSM who acquire syphilis?

can lead to visual impairment and stroke.114 Syphilis infection raises the risk of acquiring and transmitting HIV infection.

What is the name of the cells in which cervical cancer is most likely to grow?

columnar epithelial cells and squamous epithelial cells. The point where the two types of cells meet is called the transformation zone, or squamous-columnar junction. The transformation zone is vulnerable to the human papillomavirus, which can lead to cervical dysplasia or carcinoma in situ. Cells of the transformation zone are removed for examination during a Papanicolaou (Pap test) smear.

What are the serious long-term health consequences of STDs for young women?

ectopic pregnancy and infertility, other complications of STDs include pelvic inflammatory disease (PID), chronic pelvic pain, neonatal morbidity and mortality, genital cancer, and epidemiologic synergy with HIV transmission

Endometrial thickening during the proliferative phase is stimulated by increased levels of:

estrogen

Why are reproductive factors, such as early menarche and late menopause, important for the pathogenesis of breast cancer?

lifetime exposure to estrogen

How does andropause affect muscle mass?

loss of muscle mass

Which term is used to describe the thick middle layer of the uterine wall?

myometrium

What types of fibrocystic breast changes increase the risk of breast cancer?

proliferative without atypia (Epithelial hyperplasia, Sclerosing adenosis, Complex sclerosing lesion, Papillomas, fibroadenomas) proliferative with atypia (Atypical hyperplasia, atypical ductal hyperplasia, atypical lobular hyperplasia)

Which paired glands lie posterior to the urinary bladder in the male?

seminal vesicles

Spermatogenesis occurs in the

seminiferous tubules

Why is a genetic predisposition suggested for testicular cancer?

the incidence is higher among brothers, identical twins, and other close male relatives.

Which body structure contains the openings to the vagina and urinary meatus?

vestibule

What factors increase the incidence of STDs?

young people and gay and bisexual men are at greatest risk

Describe the clinical features of common disorders of the scrotum and testes, including testicular cancer.

varicocele: A dilation of the testicular vein in the scrotum, usually on the left side; In older men may result from inferior vena cava obstruction by a tumor or thrombus, which reduces blood flow through the testes, causes pooling of venous blood, and ultimately interferes with spermatogenesis and causes infertility; hydrocele: Most common cause of testicular swelling; especially common in newborns; Results from collection of fluid in the tunica vaginalis and is most often idiopathic, although secondary hydrocele can result from trauma, infection, or tumors of the testes or epididymis; In older men decreased resorption of fluid also a cause of chronic hydrocele; In infants may regress spontaneously, although surgical ligation is indicated if there is compression of the testicular blood supply spermatocele (epididymal cyst): A diverticulum (a bulging sac) of the epididymis that fills with sperm and can cause a distinct nodular mass in the scrotum; Lies outside the tunica vaginalis so it is freely mobile and easy to separate from the testes Usually asymptomatic and requires a scrotal support only if discomfort persists cryptorchidism - one or both testes fail to descend from the abdomen into the scrotum. The testicle may remain in the abdomen or arrest in the inguinal canal. Cryptorchidism is most often the result of developmental, hormonal, or structural abnormalities such as adhesions or a narrowed inguinal canal. Of greatest concern with cryptorchidism is that the testicle that remains in the abdomen may not be capable of producing sperm and is at a markedly increased risk for developing testicular cancer. Torsion of testes: Rotation of the testes that twists blood vessels of the spermatic cord Occurs most commonly in newborns and adolescents and results in the obstruction of the vascular supply to the testes with acute pain and swelling of the scrotum orchitis: Orchitis is an acute inflammation of the testicles that results from systemic infection with viruses such as mumps or may be an extension of epididymitis. In the case of mumps infection, parotitis is followed by acute pain, edema, and swelling of the scrotum with high fever and leukocytosis. Urinary symptoms are absent. epididymitis: Epididymitis generally occurs in sexually active young males (younger than 35 years) and is rare before puberty. It is acute inflammation of the epididymis, which is a densely packed coiled duct that lies within the scrotum posterior to the testicle. Bacterial infection, especially with sexually transmitted organisms such as Neisseria gonorrhoeae and Chlamydia, result in inflammation of the epididymis with pain and swelling of the scrotum and urethral discharge. Less common causes of epididymitis include other bacterial and mycobacterial infection and reflux of urine into the ejaculatory ducts. Testicular cancer: most common solid tumor of young men and majority are curable with surgery and chemotherapy. Germ cell tumors of the testes are the most common type and include': Seminoma, Embryonal carcinoma, Teratomas, Choriosarcomas; Other types of testicular carcinoma are called Leydig cell, Sertoli cell, granulosa cell, and theca cell tumors. Testicular neoplasms are usually asymptomatic and present as unilateral enlargement of the testes. They may cause a nondescript dull ache in the lower abdomen or testicular heaviness. Pain may develop if epididymitis, hemorrhage, or a hydrocele complicates tumor formation.

What event is associated with the luteal/secretory phase of the menstrual cycle?

Ovulation is the release of an ovum from a mature follicle and marks the beginning of the luteal/secretory phase

Why does puberty occur too late or too early in some individuals?

5% of cases are caused by the disruption of the hypothalamic-pituitary-gonadal axis or by the outcomes of a systemic disease

When do sex hormones first exhibit an effect on sexual development?

5th week of gestation

Define the normal age range for the onset of puberty

8-13 in girls, about 14 in boys

prostate carcinogenesis hypothesis

(1) androgens act as strong tumor promoters through androgen receptor-mediated mechanisms to enhance the carcinogenic activity of strong endogenous DNA toxic carcinogens, including reactive estrogen metabolites and estrogen, and prostate-generated reactive oxygen species; (2) reciprocal interactions between tumor cells and the stromal microenvironment promote prostate cancer pathogenesis; and (3) possibly unknown environmental-lifestyle carcinogens may contribute to prostate cancer. All of these factors are modulated by diet and genetic determinants, such as hereditary susceptibility genes and polymorphic genes, which encode receptors and enzymes involved in the metabolism and action of steroid hormones.

Where are the Bartholin glands located? What is their function?

(greater vestibular or vulvovaginal glands) open on either side of the introitus. In response to sexual stimulation, Bartholin glands secrete mucus that lubricates the inner labial surfaces, as well as enhances the viability and motility of sperm

What happens to estradiol levels in perimenopausal women?

increases

What hormones does the ovary produce?

androgens, progesterone, estrogen, activin and inhibin

Why are sex hormones necessary for reproduction?

A positive feedback loop is created with gonadotropins stimulating the gonads to produce more sex hormones. The most important hormonal effects occur in the gonads. In males, the testes begin to produce mature sperm that are capable of fertilizing an ovum. Male puberty is complete with the first ejaculation that contains mature sperm. In females, the ovaries begin to release mature ova.

What is the role of hormones and growth factors in the pathophysiology of breast cancer?

A vast majority of breast cancers are initially hormone dependent (estrogen positive [ER+] and/or progesterone positive [PR+]), with estrogens playing a crucial role in their development.127 Estrogens control processes critical for cellular functions by regulating activities and expression of key signaling molecules. These processes include regulation of receptor activity and receptor interaction with other intracellular proteins and DNA.127 Estrogens thus play prominent roles in cellular proliferation, differentiation, and apoptosis.127 Estrogens affect microtubules that are essential for establishing cell shape and cell polarity, processes necessary for epithelial gland organization. two main mechanisms of carcinogenicity of estrogens involve (1) a receptor-mediated hormonal activity shown to stimulate cellular proliferation, resulting in increased opportunities for accumulation of genetic damage; and (2) oxidative catabolism of estrogens mediated by various cytochrome complexes (P450 [CYP] system) that eventually activate and generate reactive oxygen species (ROS) that can cause oxidative stress and genomic damage directly. Oxidative metabolites of estrogens can develop ultimate carcinogens that react with DNA to cause mutations leading to carcinogenesis. Thus, imbalances in estrogen metabolites in breast tissue correlate with the development of tumors and suggest possible biomarkers related to the risk of developing breast cancer. Insulin-like growth factors (IGFs) regulate cellular functions involving cell proliferation, migration, differentiation, and apoptosis. Insulin-like growth factor 1 (IGF-1) is a protein hormone with a structure similar to that of insulin. IGF-1 is a potent mitogen, and after binding to the IGF-1R (receptor) triggers a signaling cascade leading to proliferation and anti-apoptosis. higher circulating prolactin level was associated with increased risk of in situ breast cancer.]

Why does puberty occur too late or too early in some individuals?

Delayed- 95% normal, disruption of the hypothalamic-pituitary-gonadal axis, Hypogonadotropic Hypogonadism (Decreased LH, Depressed FSH), Eugonadism; systemic disease Chronic disease, Adrenal disorders, Abnormalities of sex chromosomes, Bilateral gonadal failure, Congenital defects, Illegal drug use, Severe obesity, Strenuous exercise, weight loss/anorexia, Pituitary adenoma precocious - obesity, an increase in protein consumption, and endocrine disruptors in common household products, pesticides, plasticizers, and pharmaceuticals as well as lethal central nervous system tumors

Discuss the primary etiologic factors for sexual dysfunction and impaired fertility.

Disorders of desire -Inhibited sexual desire, decreased libido; Depression, alcohol or substance abuse; Testosterone deficiency, prolactinoma, beta-blockers Vaginismus - An involuntary muscle spasm in response to attempted penetration; Previous sexual trauma or fear Anorgasmia - Inability to achieve orgasm; Diabetes, neurologic or hormonal disturbances, pelvic disorders; narcotics, tranquilizers, antidepressants, antihypertensives dyspareunia - Painful intercourse; Inadequate lubrication caused by drugs such as antihistamines, tranquilizers, marijuana; Inadequate lubrication secondary to diabetes, vaginal infections, estrogen deficiency; Irritation and infections in the vaginal or pelvic area Infertility - Female infertility results from dysfunction of the normal reproductive process: menses and ovulation, fallopian tube function (transport of the egg to the uterus and as a site of fertilization), and implantation of the fertilized egg into a receptive endometrium. Ovarian dysfunction includes defective ovulation because of hormonal effects (e.g., PCOS, depressed hypothalamic activity, secondary physical or emotional stress), diminished ovarian reserve (lack of immature eggs secondary to congenital, medical, or unexplained factors), or premature ovarian insufficiency (failure of ovarian function before the age of 40). Fallopian tube dysfunction may result from acute pelvic infections with chlamydia or gonorrhea. Adhesions from pelvic infection, abdominal surgery, or endometriosis may cause blockage of one or both fallopian tubes, preventing access of the sperm to the ovum. The fertilized ovum must implant on a receptive endometrium.88 Receptivity may be greatly diminished by fibroids or inadequate molecular or cellular preparation of the implantation site.

Discuss the pathophysiology, assessment, and management of dysmenorrhea and amenorrhea.

Dysmenorrhea- Primary dysmenorrhea begins with the onset of ovulatory cycles, and its prevalence is highest during adolescence. The incidence steadily rises, peaks in women in the late teens and early twenties, and decreases slowly thereafter. Secondary dysmenorrhea is related to pelvic pathology conditions, manifests later in the reproductive years, and may occur any time in the menstrual cycle.Primary dysmenorrhea is the result of excessive prostaglandin F2 alpha levels in the myometrium and endometrium, resulting in excessive uterine contractions and endometrial shedding. The elevated prostaglandin levels can also have systemic effects, including headache, nausea, abdominal cramping, and diarrhea. Begins at the onset of menses, Is related to length and amount of menstrual flow, Is usually crampy in nature, May be felt in both the pelvic region and low back and radiate to the groin. Symptoms usually resolve gradually over the next 2 days. Evaluation requires a pelvic examination to rule out secondary causes. Management with nonsteroidal anti-inflammatory drugs (which block prostaglandin production) is usually successful and must be started at, or even before, the onset of menses. Other treatments include oral contraceptives, exercise, local heat, massage, and relaxation techniques. Amenorrhea - The potential causes of primary amenorrhea are varied and include genetic and congenital disorders that affect gonadotropin production, maturation of the ovaries or uterus, or the CNS. Individuals with primary amenorrhea require thorough physical examination and laboratory and radiographic evaluation followed by surgical or hormonal correction if possible. Secondary amenorrhea is the absence of menstruation for a time equivalent to three or more cycles or 6 months in women who have previously menstruated. The most common causes of secondary amenorrhea are menopause and pregnancy. Other causes include extreme weight loss, eating disorders, ovarian or uterine disease, chemotherapy, toxins, pituitary tumors (prolactinoma), thyroid disorders, and CNS trauma. Depending on the underlying cause of the amenorrhea, infertility, vasomotor flushes, vaginal atrophy, acne, osteopenia, and hirsutism (abnormal hairiness) may be present. Management is specific for the underlying condition but often includes hormone therapy or corrective surgery.

Discuss the pathophysiology and clinical manifestations of benign and malignant cervical, vaginal, vulvar, endometrial, and ovarian tumors.

Endometrial polyps and leiomyomas are benign growths of the uterine lining (endometrium) or muscle (myometrium) that can cause dysfunctional uterine bleeding. Endometrial polyps consist of an accumulation of the following: Endometrial glands Stroma, Blood vessels that arise from the uterine fundus or upper endocervix. The polyps can be described as hyperplastic, atrophic, or functional. Most are asymptomatic but can cause dysfunctional uterine bleeding. Leiomyomas are benign growths that arise from the myometrial smooth muscle and are commonly called uterine fibroids. They are classified by their location: subserous, submucous, or intramural. Leiomyomas often occur as multiple small tumors, and most remain asymptomatic, although cramping, abdominal pressure, and dysfunctional uterine bleeding can occur. Their size is related to hormonal fluctuations. Pressure on surrounding structures such as bladder and rectosigmoid can also cause symptoms. cervical cancer - Cervical cancer is commonly asymptomatic and is usually detected by Pap smear. When present, manifestations may include the following: Change in vaginal discharge, Vaginal bleeding, especially after intercourse vaginal cancer - progresses from cervical intraepithelial neoplasia to carcinoma in situ to invasive carcinoma. Vaginal cancer is usually asymptomatic but may also be associated with abnormal vaginal bleeding or discharge not related to menstrual periods, pain during intercourse, pain in the pelvic area, pain when urinating, and constipation. Vulvar cancer - rare and typically occurs as squamous cell carcinoma. Urinary symptoms and discharge rarely, Hard, ulcerated area of the vulva, Large lesions of vulva endometrial cancer- Abnormal vaginal bleeding, Pain, Weight loss ovarian cancers - arise from the surface epithelium of the ovary and spread intra-abdominally over the surface of the peritoneum. Loss of tumor suppressor gene ARID1A function is associated with ovarian carcinomas. usually asymptomatic, and when symptoms occur, the disease has spread beyond the ovaries. One of the most common and ominous symptoms is painless ascites and bloating sensation resulting from widespread seeding of the peritoneum. Other symptoms include the following: Abdominal, back, or pelvic pain; Anorexia and early satiety; Constipation; Vaginal discharge or bleeding; Hypercoagulability with venous and arterial clot formation; Urinary urgency or frequency; Dyspareunia and pelvis pressure

What is the difference between a follicular cyst and a corpus luteum cyst?

Follicular cysts (also called ovarian or functional cysts) are filled with fluid and can be caused by a transient condition in which the dominant follicle fails to rupture or one or more of the nondominant follicles fails to regress. A corpus luteum cyst may normally form by the granulosa cells left behind after ovulation. Corpus luteum cysts are less common than follicular cysts, but luteal cysts typically cause more symptoms, particularly if they rupture.

Why is complete breast involution important for reducing risk of breast cancer?

Having a combination of dense breasts and no lobular involution was associated with higher breast cancer risk than having nondense or fatty breasts and complete involution. Women with dense breasts occupying more than 60% to 75% of the breast have a fourfold to sixfold increased risk of breast cancer compared with those with little or no density. Dense area percentage is a stronger breast cancer risk factor than absolute dense area. Mammographic dense tissue has been thought to represent both epithelial and stromal components.

Why does menstruation occur?

If conception and implantation do not occur, the corpus luteum degenerates and ceases its production of progesterone and estrogen. Without progesterone or estrogen to maintain it, the endometrium enters the ischemic ("blood-starved") phase and disintegrates

How does breast development differ between adult men and women?

In the absence of sufficiently high levels of estrogen and progesterone, and with antagonistic effects of androgens, the male breast does not develop any further after puberty; consists mostly of fat with a small, underdeveloped nipple and a few ductlike structures in the subareolar area. The male breast may appear enlarged in obese men because of accumulation of fatty tissue.

Discuss insulin resistance, hyperinsulinemia, anovulation, and androgen production in PCOS.

Insulin resistance and resultant compensatory hyperinsulinemia overstimulates androgen secretion by the ovarian stroma and reduces hepatic secretion of serum sex hormone-binding globulin (SHBG). The net effect is an increase in free testosterone levels. Excessive androgens affect follicular growth, and insulin affects follicular decline by suppressing apoptosis and enabling the survival of follicles that would normally disintegrate. Further, there seems to be a genetic ovarian defect in PCOS that makes the ovary either more susceptible to or more sensitive to insulin's stimulation of androgen production in the ovary. Inappropriate gonadotropin secretion triggers the beginning of a vicious cycle that perpetuates anovulation. Typically, levels of follicle-stimulating hormone (FSH) are low or below normal, and the luteinizing hormone (LH) level is elevated. Persistent LH level elevation causes an increase in the concentration of androgens (dehydroepiandrosterone sulfate [DHEAS] from the adrenal glands and testosterone, androstenedione, and dehydroepiandrosterone [DHEA] from the ovary). Androgens are converted to estrogen in peripheral tissues, and increased testosterone levels cause a significant reduction (approximately 50%) in SHBG level, which, in turn, causes increased levels of free estradiol. Elevated estrogen levels trigger a positive feedback response in LH and a negative feedback response in FSH. Because FSH levels are not totally depressed, new follicular growth is continuously stimulated, but not to full maturation and ovulation

Identify the common sexually transmitted infections.

Many bacterial STIs are asymptomatic or cause genital discharge as the primary manifestation. The following are clinical manifestations specific to certain infections: Chancroid: inflamed genital ulcer in men; asymptomatic in women; Lymphogranuloma venereum (LGV): genital skin lesions that spread to lymphatics; Syphilis: hard chancre, low-grade fever, sore throat, malaise, hoarseness, anorexia, headache, joint pain, and rashes; left untreated, leads to neurologic impairment and life-threatening hypersensitivities; Typically, bacterial infections that are not treated with antibiotics lead to infertility. In females, pelvic inflammatory disease is the primary manifestation. protozoan STI is trichomoniasis. In males this infection usually resides in the urethra and is asymptomatic. In females this infection produces a copious frothy vaginal discharge that may have a fishy odor, pain during intercourse, dysuria, and internal pruritis. The infection is completely curable with antibiotics. Phthirus pubis (crabs) and Sarcoptes scabiei (scabies) are the most common parasitic STIs. Both of these infections cause intense itching that may lead to skin conditions secondary to scratching. Treatments include creams, shampoos, and lotions. The most common source of viral STI in the United States is human papillomavirus (HPV). Other sources of infection include genital herpes (HSV1 or HSV2); hepatitis A, B, and C; and human immunodeficiency virus (HIV). As previously mentioned, viral STIs are currently incurable. There are, however, vaccinations for hepatitis A and B and the most common types of HPV. In addition, there are drugs to lessen the symptoms of herpes and hepatitis. The following clinical manifestations are typically seen with viral STIs: HPV: genital warts; cervical, vulvar, or penile cancer; Genital herpes: genital ulceration; Hepatitis: liver disease or cancer, jaundice, low-grade fever, initially flulike symptoms HIV: progression to AIDS

Compare and contrast the pathophysiology and clinical manifestations of pelvic inflammatory disease, vaginitis, cervicitis, vulvitis, and bartholinitis.

PID - PID can occasionally be caused by organisms that migrate from other sources of infection, such as the vagina or colon. It can also be caused by immune suppression with associated overgrowth of the normal vaginal flora. Although PID can be initiated by gonorrhea or chlamydial infection, most cases are caused by mixed nongonococcal/nonchlamydial bacteria sudden severe abdominal pain with fever to no symptoms at all. The first sign of the ascending infection may be the onset of low bilateral abdominal pain, dull and steady with a gradual onset. Symptoms develop during or immediately after menstruation, and pain worsens with walking or jumping. Dyspareunia, dysuria, and irregular bleeding vaginitis - Vaginitis can be caused by infection with sexually transmitted organisms or by the disruption of the normal defense mechanisms with overgrowth of normal flora. Cervicitis - Cervicitis is most commonly caused by STIs, especially trichomonal and chlamydial infections and gonorrhea. Cervical discharge becomes purulent and foul smelling, and pelvic pain, vaginal bleeding, or dyspareunia are common. vulvitis - inflammation of the vulva and/or vaginal vestibule, Most commonly the result of irritation of the skin caused by soaps, detergents, lotions, shaving, feminine hygiene products, excessive sweating, or menstrual pads, Can also be caused by infectious organisms such as Candida albicans and by trichomoniasis. May be present secondary to an autoimmune reaction Bartholinitis - Inflammation of Bartholin ducts; can be complicated by duct obstruction, stasis of glandular secretions, and abscess formation in the glands themselves. Most commonly results from infection by streptococci, staphylococci, and sexually transmitted pathogens; affected area is red and painful

What is the current understanding of hormones in the pathophysiology of prostate cancer?

Prostate cancer develops in an androgen-dependent epithelium and is usually androgen sensitive. Androgens are synthesized not only in the testis, accounting for 50% to 60% of the total testosterone in the prostate, but also in the prostate gland itself. Androgens also are metabolized to estrogens (see Figure 34-14, B) through the action of the enzyme aromatase, and a growing body of evidence implicates estrogens in the etiology of prostate disease Prostate cancer is considered a hormone-dependent disease; cell growth and survival of early stage prostate cancer can respond to androgens and this is the background evidence for androgen-deprivation therapy (ADT). stromal androgen receptor was essential for prostate cancer progression, malignant transformation, and metastasis. DHT is the most potent intraprostatic androgen. estrogens participate in the pathogenesis and development of benign prostatic hyperplasia and prostate cancer by activating estrogen receptor α (ER-α). ER-α leads to abnormal proliferation, inflammation, and the development of premalignant lesions. Increased expression of ER-α has been found to be associated with prostate cancer progression, metastasis, and the so-called castration-resistant (medical treatment that suppresses androgens) phenotype (1) androgens are clearly involved in the progression of prostate cancer; (2) it is only with the addition of estrogen to testosterone in rats that cancer can be reliably induced; (3) in vivo and in vitro studies have identified multiple mechanisms 871involving hormonal involvement with genotoxicity, epigenetic toxicity, hyperprolactinemia, chronic inflammation, and estrogen receptor-mediated changes.

Describe what is meant by prostate cancer cell and stromal interactions for carcinogenesis.

Reciprocal interactions between tumor cells and stromal components influence the metastatic, dormancy-related, and stem cell-like potential of tumor cells.92 The stromal compartment of the tumor is complex and includes inflammatory/immune cells, vascular endothelial cells, pericytes, fibroblasts, adipocytes, and components of the extracellular matrix.91,93 Tumor-infiltrating inflammatory cells release a host of growth factors, chemokines, cytokines, and proinvasive matrix-degrading enzymes to promote tumor growth and progression.91 Angiogenesis occurs in response to factors secreted from tumor cells, resulting in continued growth and progression. Adipocytes in the tumor microenvironment produce adipokines, which are important for tumor growth.91 Fibroblasts in the tumor microenvironment provide the structural framework of the stroma; they remain quiet or dormant, but proliferate during wound healing, inflammation, and cancer.91 Tumor cells release paracrine factors that activate fibroblasts to become "cancer-associated fibroblasts" (CAFs). CAFs secrete factors that modulate tumor growth and modify the stroma to enhance metastasis and dampen responses to anticancer therapies

Discuss the risk factors, pathophysiology, clinical manifestations, evaluation, and treatment of breast cancer.

Risk factors: Positive family hx, environmental including Radiation, diet, exercise, alcohol patho: Genetic vulnerability interacts with environmental carcinogens and exposure to growth factors such as estrogen and progesterone to cause progressive mutations in the cellular DNA of the glandular breast tissue. Multiple molecular genetic pathways affect progression of normal breast epithelial cells to transform these cells to invade, resist apoptosis, and disseminate. Sporadic clonal evolution model: Any breast epithelial cell could be the target of mutation (genetic or epigenetic) over time. Cancer stem cell model: Only progenitor stem cells within a tumor are targets for neoplastic cell replication. Breast cancer cells that retain their normal estrogen and progesterone receptors (ER and PR positive) are less anaplastic and more responsive to pharmacologic blockade of estrogen and progesterone growth factors. If the cancer cells have lost their estrogen and progesterone receptors (ER and PR negative), they are able to sustain their own accelerated cell division through autocrine production of insulin-like growth factor, transforming growth factor, and epidermal growth factor. The final steps in carcinogenesis of breast cells involve further mutations that allow the tumor to extend locally into surrounding tissues (e.g., production of matrix proteases) and then metastasize to bone, lung, brain, and other organs. SX: Breast cancer is commonly found on screening breast self-examination and mammography and other than a painless lump is usually asymptomatic. advanced tumors include the following: Pain in the breast, Dimpling of the skin, Nipple retraction or discharge, Edema of the arm, Enlargement of the axillary lymph nodes, Symptoms such as bone pain, dyspnea, or neurologic deficits are indicative of metastasis TX: combination of surgical removal of the primary tumor followed by hormonal therapy and/or chemotherapy, depending on the stage of the tumor. Other management techniques include administration of bisphosphonates to treat bone metastases and psychological intervention to improve quality of life and immune function.

What are the risk factors and pathogenesis for endometrial cancer?

The primary risk factor is unopposed estrogen exposure (without progesterone). Exposure to unopposed estrogen includes estrogen-only hormone replacement therapy, tamoxifen, early menarche, late menopause, never having children, and a failure to ovulate (i.e., PCOS and anovulatory cycles typical of the late reproductive years). Less is known about the association with other types of hormone therapy. Chronic hyperinsulinemia, hyperglycemia, body fatness and adult weight gain, chronic inflammation, and lack of physical activity confer an increased risk of endometrial cancer use of long-cycle estrogen and progestin hormone replacement therapy (HRT), gallbladder disease and hypertension, although being overweight may be a mediating factor for these risks. A family history of colon, endometrial, or ovarian cancer could signal hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome

Describe the common manifestations of pelvic relaxation disorders.

Urinary: Sensation of incomplete emptying of bladder Urinary incontinence Urinary frequency/urgency Bladder "splinting" to accomplish voiding Bowel: Constipation or feeling of rectal fullness or blockage Difficult defecation Stool or flatus incontinence Urgency Manual "splinting" of posterior vaginal wall to accomplish defecation Pain and Bulging Vaginal, bladder, rectum: Pelvic pressure, bulging, pain Lower back pain Sexual: Dyspareunia Decreased sensation, lubrication, arousal

What is the purpose of prostatic secretion?

a thin, milky substance with an alkaline pH that helps sperm to survive in the acidic environment of the female reproductive tract ans help to mobilize sperm after ejaculation

What are the physical changes associated with menopausal decreases in estrogen level?

breasts are reduced in size and firmness, ovaries shrink; the uterus atrophies; and the vagina shortens, narrows, and loses some elasticity. Lubrication of the vagina diminishes and vaginal pH increases, cervix atrophies; the cervical os shrinks; vaginal epithelium atrophies; labia major and minora become less prominent; some pubic hair is lost; urethral tone declines along with muscle tone throughout the pelvic area; urinary frequency or urgency, urinary tract infections, and incontinence may occur, Bone mass is lost, leading to increased brittleness and porosity and possibly osteoporosis particularly in the lumbar spine and femoral neck , Vasomotor flushes

What is the cause of male gynecomastia?

hormonal alterations, which may be idiopathic or caused by systemic disorders, drugs, or neoplasms.

What factors reduce the risk of ovarian cancer?

factors that suppress ovulation (pregnancy, breast-feeding, and combined hormonal contraceptive use)

Describe the common causes of abnormal uterine bleeding.

failure to ovulate secondary to age, stress, endocrinopathy, malignancy, or abnormal bleeding pattern. The majority of DUB is caused by anovulatory cycles when progesterone is absent and estrogen continues to be secreted unopposed. Unopposed estrogen causes irregular endometrial thickening and increases vascularity. As a result, menstrual flow is irregular, excessive, or both

Why do benign ovarian cysts develop in women who ovulate?

follicular cysts and corpus luteum cysts. These cysts are called functional cysts because they are caused by variations of normal physiologic events. a follicle or a number of follicles are stimulated but no dominant follicle develops and completes the maturation process.

Why does amenorrhea occur?

hypothalamic dysfunction, polycystic ovarian syndrome, hyperprolactinemia, and ovarian failure Compartment I disorders are anatomic defects, including absence of the vagina and uterus. Compartment II disorders involve the ovary, primarily genetic disorders and androgen insensitivity syndrome (AIS). The target organs in AIS are completely resistant to the action of androgens, resulting in a lack of estrogen. Compartment III disorders are of the anterior pituitary gland, including tumors, and result in failure of signaling to the ovaries through follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Compartment IV disorders include central nervous system (CNS) disorders and primarily involve hypothalamic defects that prevent secretion of gonadotropin-releasing hormone (GnRH); thus, there is no signaling to the pituitary to release FSH and LH. Secondary amenorrhea is common (normal) during early adolescence, pregnancy, lactation, and the perimenopausal period, primarily because of anovulation. The most common causes (after pregnancy) are thyroid disorders (e.g., hypothyroidism); hyperprolactinemia; hypothalamic-pituitary-ovarian (HPO) interruption secondary to excessive exercise, stress, or weight loss; and polycystic ovary syndrome (PCOS). stress, extreme exercise, large dietary changes, eating disorders, or sleep abnormalities. Hypothyroidism

Why is the worldwide variation of prostate cancer incidence important?

incidence rates vary by more than 25-fold worldwide, with the highest rates recorded mostly in developed countries, such as Oceania, Europe, and North America, largely because of wide use or overuse of PSA testing. Screening with PSA can amplify the incidence of prostate cancer by allowing detection of prostate lesions that, although meeting the pathologic criteria for malignancy, may have low potential (e.g., latent, indolent, preclinical) for growth and metastasis.

What are the current theories of pathophysiology for PMS/PMDD?

increased vulnerability to fluctuations in ovarian-derived hormones, and hypothalamic-pituitary-adrenal (HPA) axis changes. Poorly understood are the neuroendocrine mechanisms of the hormonal environment of the menopausal transition that might trigger depression. Erratic ovarian hormone fluctuation may be a mediator of risk for both vasomotor symptoms (hot flashes) and perimenopausal depression. Under investigation are the effects of changes in estradiol concentrations and the altered anti-inflammatory and neuroprotective consequences and modulation of limbic processing and memory. Neurotransmitters, such as serotonin, gamma-aminobutyric acid (GABA), and norepinephrine, have demonstrated interactions with estrogen and progesterone and have established mood and behavior effects, including negative mood, irritability, aggression, and impulse control. Additionally, neurotransmitters may have mediating or moderating roles on symptom manifestation. Sex steroids also interact with the renin-angiotensin-aldosterone system (RAAS), which could explain some PMS/PMDD signs and symptoms (e.g., water retention, bloating, weight gain). Levels of inflammatory mediators may be elevated with menstrual symptom severity and PMS. A predisposition to PMS occurs in families, perhaps because of genetics or shared environment. A woman's menstrual experience is often similar to her mother's or her sister's experience. Evidence supports a relationship between severity and frequency of PMS/PMDD and reports of low well-being, major affective disorder, and personal characteristics, such as increased stress, poor nutrition, lack of exercise, low self-esteem, perfectionism, history of sexual abuse, and family conflict. In turn, when PMS/PMDD is distressing, the quality of interpersonal relationships and self-image are negatively affected.

Why is epididymitis rare in prepubescent males?

it generally occurs in sexually active young males and the usual cause is a sexually transmitted microorganism, such as N. gonorrhoeae or C. trachomatis

Why is testicular torsion considered a urologic emergency?

it reduces and stops circulation to the testis and surgery must be performed within 6 hours after the onset of symptoms to preserve normal testicular function.

Why is the ovary the most essential female reproductive organ?

ovaries are the site of (1) ovum maturation and release and (2) production of female sex hormones

Why are priapism and severe paraphimosis considered urologic emergencies?

paraphimosis - prevent necrosis of the glans caused by constricted blood vessels priapism - prevent impotence

Compare and contrast the pathophysiology and clinical manifestations of phimosis, Peyronie disease, priapism, balanitis, and penile cancer.

phimosis: Phimosis is the condition in which the foreskin cannot be retracted over the glans (see A in the image on this screen), and paraphimosis is the condition in which the foreskin is retracted and cannot be reduced over the glans patho-scarring and resultant adhesions resulting from poor hygiene and infection. sx- Edema of the glans with tenderness of the prepuce; Inflammation of the glans or prepuce along with purulent discharge; Increased risk of penile cancer Peyronie: (bent nail syndrome) is a chronic condition patho- idiopathic vasculitis and inflammation cause a gradual fibrosis of the fascia in the erectile tissue of the corpora cavernosa, causing curvature of the penis during erection. It results from fibrosis of the fascia on the lateral side of the penis, resulting in curvature of the penis. sx - Dyspareunia, Impotence, Painful erection priapism: prolonged, painful penile erection patho- usually idiopathic and not associated with sexual arousal and can be associated with intracavernous injection therapy for impotence, spinal cord disease, sickle cell disease, trauma, and pelvic tumors. Priapism is considered a medical emergency; left untreated it is associated with long-term erectile dysfunction. balanitis: inflammation of the glans patho- most often caused by phimosis or poor hygiene with resultant accumulation of glandular secretions under the foreskin (smegma) and infection with Mycobacterium smegmatis., associated with candidiasis and poorly controlled diabetes. penile cancer: patho-Precancerous lesions such as leukoplakia and condylomas progress to carcinoma in situ and finally squamous cell carcinoma that begins as a small ulcerative lesion but can progress to involve the entire shaft of the penis. sx - late stages -Pain, Swelling of the femoral and iliac nodes, Weight loss, Fatigue and malaise

Why do sperm take 12 days to travel the length of the epididymis?

when the sperm enters, they are not fully mature, so they receive nutrients and testosterone and their capacity for fertilization is enhanced