Review for the Final Exam

Biol E-163

1/8/06

Conditions/Diseases of the Reproductive System

MALE FEMALE

From: Vander’s Human Physiology, 10th edition, E Widmaier, H Raff, and K Strang

The Menstrual Cycle

• From Human Reproduction at a Glance, L.J. Heffner

Erectile Dysfunction

• 1/3 phsychological, 1/3 physical, 1/3 combination

• Causes: Neurologic problems, circulatory problems, low testosterone levels, diabetes mellitus (neuropathy and circulatory problems)

• Treatment– Viagra= stimulates release of NO dilates blood

vessels erection– Inflatable prosthetic devices implanted in penis

Female Sexual Dysfunction

• Low levels of testosterone decrease sex drive– Treatment = testosterone patches

• Impaired blood flow to genital area– Treatment = prostaglandin E1

Spinal Cord Injury• Male

– Erection (parasympathetic NS) and ejaculation (sympathetic NS) require intact spinal cord

• Most men with spinal cord injuries are impotent

– Can harvest sperm from testes

• Female– ~50% of women with spinal cord injury

retain sexual responsiveness, particularly if sacral region is intact

– Injury to T11-L2 region, involved with innervation to the genitals, is associated with loss of sexual function

From: http://www.sci-info-pages.com/levels.html

Precocious Puberty

• Definition = signs of puberty before age 8 in girls or before age 9 in boys

• Causes:– GnRH secreting tumors– Topical exposure to repro hormones– Hormones in meats, estrogen analogs in plastics, pesticides, etc.– Overweight, especially low birth weight rapid weight gain in

infancy/childhood• Consequences

– Shorter than expected adult height– Overweight PCOS and ↑ cancer risk– Social issues

• Treatment – Lupron (mimics GnRH) = constant administration suppresses

hypothalamic/anterior pituitary access, i.e. suppresses FSH & LH release, thereby reducing estrogen production

Late Puberty

• Definition = initial signs of puberty after age 13 in girls or after age 14 in boys

• Causes:– Insufficient GnRH or abnormal patterns of release– Insufficient % body fat or low weight, leptin (produced

by adipose tissue) seems to be important for timing– Excessive exercise

• Consequences– Impaired fertility (reversible)– Bone loss in young women

Infertility• Definition = a couple is unable to conceive after 1 year of

unprotected intercourse• In developed countries, 10-15% of couples are sub-fertile• Types:

– Primary infertility = infertility in the absence of prior pregnancy– Secondary infertility = infertility after previous pregancy

• Male and female factors– ~30% involve just the man– ~50% involve just the woman– ~20% involve both partners

• Infertility rates have risen– More women in late reproductive years as the population ages– More women delay childbearing– More couples seek fertility treatments

• Success rates– ~half of infertile couples will eventually conceive– Assisted reproductive technologies (ART) have increased

pregnancy rates

Male Factors in Infertility (1)1. Inability to ejaculate

• Caused by neural injury or disease (such as spinal cord injury, diabetic neuropathy, multiple sclerosis)

• Treatment -adrenergic agonists = facilitate ejaculation by ↑ peristalsis and

closure of bladder• Sperm can be retrieved for IVF or artificial insemination

2. Blockage of epididymis• Congenital or result of infection• Treatment

• Sperm can be retrieved for IVF or artificial insemination

3. Retrograde ejaculation• Some or all of ejaculate enters the bladder• Treatment

-adrenergic agonists = facilitate ejaculation by ↑ peristalsis and closure of bladder

Recover sperm from bladder for IVF or artificial insemination

Male Factors in Infertility (2)

4. Immunologic infertility• Presence of anti-sperm antibodies• Can be side-effect of vasectomy

• Immune system is not usually exposed to sperm due to Sertoli-cell barrier

• During procedure, some sperm can leak out of seminiferous tubules and trigger immune response

• Treatment • High doses of corticosteroids = inhibit immune system

5. Hypogonadotrophic hypogonadism • Low levels of FSH and LH• Causes low sperm count (~100-700 million sperm/ejaculation

are necessary for normal fertility)• Treatment

• FSH and LH• GnRH

Male Factors in Infertility (3)

6. Defects in spermatogenesis• Can cause abnormal/ slow moving/ or dead sperm

7. Lifestyle factors• Anabolic steroids = negative feedback inhibition on GnRH• Hot tubs/ tight briefs = ↑ temp of testes• Bicycle riding = injury to testes

Female Factors in Infertility (1)1. Tubal obstruction

• Accounts for ~36% of fertility disorders• Diagnosed by injecting dye through cervix and monitoring

movement through uterine tubes• Usually occurs secondarily to tubal infection and fibrosis

2. Disorders of ovulation• Accounts for ~33% of fertility disorders1. Hyperprolactinemia

• caused by pituitary tumors or stress• If stress-induced, treat with bromocriptine (a dopamine agonsist)

because dopamine released from hypothalamus inhibits prolactin release

2. 1o hypothalamic failure• GnRH deficiency low FSH & LH low estrogen failusre to

ovulate• Treatment with pulsatile administration of GnRH

Female Factors in Infertility (2)

2. Disorders of ovulation continued…3. Hypothalamic-pituitary failure

• FSH & LH secretion is insufficient• Treatment with Clomid administered on days 5-9 of cycle

• Antiestrogenic effect on hypothalamus reduces negative feedback of estrogen during early follicular phase increased release of FSH & LH

• Also ↑ ovarian sensitivity to gonadotropins• ~80% will ovulate after treatment, ~50% become pregnant,

~5-10% of resulting pregnancies will be multiple births

• Treatment with Pergonal during follicular phase to stimulate follicular maturation• Contains FSH & LH• Also administer human chorionic gonadotropin (hCG)

midcycle to stimulate ovulation• ~15-3% of resulting pregnancies will be multiple births

Female Factors in Infertility (3)2. Disorders of ovulation continued…

4. Polycystic ovary syndrome (PCOS)• Associated with failure to ovulate• Characterized by irregular menstrual periods, androgen

excess, obesity, and insulin resistance• Underlying problem is excess of LH stimulates

androgen production by theca cells of ovary– Some androgens converted to estrogens by granulosa cells

maintains constant level of estrogen instead of cyclic

– Estrogen levels are at levels found in early/mid follicular phase triggers GnRH release follicles develop but no late-follicular rise in estrogen or LH surge ovulation does not occur

• Ovaries develop cysts in response to stimulated follicles

Female Factors in Infertility (4)3. Endometriosis

• Accounts for ~6% of fertility disorders• Appearance of endometrial tissue outside of uterus that

responds to reproductive hormones in the same way that the uterine lining does (thickening and shedding)

• Not malignant• Cause unknown, but has genetic tendency• Fertility rates are ~half those of women without disease

• Severity not correlated with likelihood of infertility• Scarring of ovaries or fallopian tubes may occur, but women

without scarring may still be infertile• Alterations to immune milieu in pelvic area, may interfere with

ovulation, fertilization, or implantation• Some evidence of ovulatory dysfunction

• Pain management with birth control pills, GnRH analogs (Lupron), or surgery

• May also help to preserve fertility

4. ~40% of infertile women show no obvious cause

Assisted Reproductive Technologies (ARTs)

• Involve retrieving eggs from ovaries, fertilizing, and reimplanting them– Ovulation is chemically induced by fertility drugs and

eggs are harvested

• Success rates– For IVF, delivery rates are ~22.5% / procedure– Success is lower for older women

• Risks– Mainly from multiple births (~37%)

Spontaneous Abortion

• Miscarriage of a fetus prior to age of viability (defined as 20 weeks from last period)

• Rate of miscarriage is difficult to calculate since many conceptions fail before pregnancy is recognized

• ~75% of miscarriages occur in the first 12 weeks• Causes

– ~half due to chromosomal abnormalities of the fetus– Weak cervical muscles, ectopic implantation, hemolytic

disorders, etc.– Environmental factors may also increase likelihood (exposure to

X-rays, certain viruses, toxins, alcohol, cigarette smoke)

• Even after 2 miscarriages, there is a 70% chance of having a successful pregnancy

Testicular Cancer

• Occurs more frequently in younger men, most common cancer in men between ages 15-34

• Incidence is rising• Cause unknown• Risk factors

– Testicular dysgenesis syndrome (TDS) = congenital malformation of the testes

– Exposure to natural estrogen or endocrine disruptors in utero or during childhood

• Treatment– Removal of affected testes

Prostate Cancer

• Most common cancer in men• Incidence is rising, but may be due to screening

by PSA test• Most cases diagnosed in men >65, but

diagnosis at younger ages is associated with more aggressive disease

• Potential risk factors: fat consumption, obesity, STDs

• Treatment– Surgery– Radiation– Hormonal therapy to suppress testosterone levels

Breast Cancer (1)• Most common reproductive cancer in women• Incidence rose in 1980’s, but rate of increase

has slowed since then• Odds of ever developing breast cancer in

lifetime is 1 in 8 women• More common in industrialized countries• Can occur in men (accounts for ~1% of breast

cancers)• Signs and symptoms

– Usually detectable by mammography before symptoms appear

– Breast lump, thickening, swelling, distortion, tenderness, changes in nipple shape/texture

Breast Cancer (2)• Estrogen related risk factors

– Nulliparity or late first pregnancy– Early menarche & late menopause– Prolonged estrogen therapy– Use of older forms of birth control pills– Obesity after menopause– Alcohol use– Xenoestrogens (“foreign estrogens) in environmental agents

• ‘bad’ xenoestrogens = DDT, plastics, pharmacologic agents, and other compounds that act as estrogen agonists in breast tissue

• ‘good’ xenoestrogens = found in certain foods that act as estrogen antagonists in breast tissue

• Lifestyle factors – Vigorous physical activity associated with lower risk

• Genetic risk factors– Responsible for 5-10% of all breast cancers– Most commonly studied are BRCA1 and BRCA2

• Also associated with ovarian cancer• Tumor suppressor genes

Breast Cancer (3)• Treatment

– Surgery– Radiation– Chemotherapy– Hormone therapy

• ex: tamoxifen = estrogen antagonist in breast tissue, but acts as estrogen agonist in endometrial tissue

• 5 year survival rates– 98% for localized disease– 81% for regional spread– 26% for distant metastases

Cervical Cancer• Incidence has decreased with widespread screening by

Pap smear• Signs and symptoms

– Abnormal vaginal bleeding or discharge– Pain

• Pap smears aid in early detection of dysplasia before cells become cancerous

• Risk factors– HPV infection with certain high-risk strains– Early age of first sexual encounter and multiple partners– Cigarette smoking

• Treatment– Pre-invasive lesions: cryotherapy, electrocoagulation, laser

ablation, local surgery– Invasive cancers: surgery and/or radiation

• 5 year survival rates– Pre-invasive: nearly 100%– Localized cancer: 92%– All stages: 70%

Endometrial Cancer (1)

• Most common gynecologic cancer in the U.S.• 1-3% of women will be diagnosed with endometrial

cancer before age 75• Signs and symptoms

– Abnormal uterine bleeding– Pain

• Estrogen related risk factors– Nulliparity or late first pregnancy– Early menarche & late menopause– Post-menopausal hormone therapy– History of ovulatory failure– Estrogen-secreting tumors and PCOS– Prior treatment of breast cancer with tamoxifen– Use of older forms of birth control pills– Obesity– Alcohol use

Endometrial Cancer (2)

• Genetic factors– Likelihood of endometrial cancer does not appear to

be strongly linked with genetics– Women with a history of breast or ovarian cancer are

at higher risk

• Treatment– Surgery, followed by radiation and chemotherapy

• 5 year survival rates– 96% for localized disease– 63% for regional spread– 26% for distant metastases

Ovarian Cancer (1)

• Occurs in 1-2% of women in developed countries

• Tends to develop later in life• Causes more deaths than any other cancers of

the female repro tract• Signs and symptoms

– Very difficult to detect! – Enlargement of abdomen– Digestive disturbances

Ovarian Cancer (2)• Elevated risk associated with prolonged exposure to

high levels of gonadotropins (FSH & LH)– Nulliparity increases risk = pregnancy sharply reduces

gonadotropin secretion– Birth control pills reduce risk = further suppress FSH and LH

release– Depletion of oocytes increase risk = less inhibin and estrogen

in circulation to suppress gonadotropin release• May explain elevated risk with increasing age

– Use of fertility drugs increases risk = increases blood levels of FSH and LH

• Genetic factors– Not strongly genetic

• Treatment – Surgery, radiation, chemotherapy

• 5 year survivial rates– Localized cancer: 95%– All stages: 52%

Conditions/Diseases of the Gastrointestinal System

Gastroesophageal Reflux (1)

• The lower esophageal sphincter (LES) is located in the abdominal cavity and is controlled by smooth muscle

• If the LES stays open too long, gastric contents can enter the esophagus and cause heartburn– can happen as a result of a hiatal hernia

• LES is pushed into thoracic cavity (lower pressure than abdominal cavity)

• Risk factors– Infancy = sphincters are more poorly developed– Obesity = higher pressure in abdominal cavity– Pregnancy = “ “– Postural changes– Smoking– Certain foods (peppermint, coffee, alcohol)– Having SLE

Gastroesophageal Reflux (2)

• Consequences– Heartburn– Barrett’s esophagus = repeated exposure to stomach

acids changes nature of epithelial lining of esophagus ↑ risk of esophageal adenocarcinoma

– Damage to tooth enamel

• Treatment– Lifestyle changes (lose weight, smoking cessation,

change diet, etc.)– Drugs that inhibit acid secretion– Surgery to correct hiatal hernia

Peptic Ulcers and IBS

• Covered in TA session

Vomiting• Forceful emptying of stomach and intestinal contents

through the mouth– Reflex is controlled by the medulla

• Can cause:– Distention of stomach and duodenum– Pain– Dizziness– Nausea– Hypersalivation– Tachycardia – Sweating

• Consequenses:– Dehydration = due to loss of fluids– Metabolic alkalosis = due to loss of acidic fluids– Hypokalemia = aldosterone is released as a result of low blood

volume in kidney, causes increased Na+ reabsorption and increased K+ excretion

– Malnutrition = loss of calories in vomitus

Diarrhea (1)

• Definition = stool volumes of > 250 g / day (normal is 100 g/day)

• Leading cause of death worldwide – accounts for > 4 million deaths per year of children under age 5

• Can result in metabolic acidosis and hypokalemia since K+ and HCO3

- concentrations are higher in fluid in colon than serum

Types of Diarrhea1. Osmotic = caused by retention of unabsorbable

substances in the intestines, water follows by osmosis• Example: Lactose intolerance

2. Secretory = caused by excessive intestinal mucosal secretion of large volumes of fluid and electrolytes

– Usually caused by bacterial toxins or viruses– Example: cholera

Diarrhea (2)

3. Malabsorption = caused by the presence of unabsorbed material in the gut, water follows by osmosis

– Example: celiac disease• Intolerance to gluten or gluten byproducts • Autoimmune disease• Loss of intestinal epithelium also contributes to diarrhea by

decreasing surface area of gut, loss of intestinal epithelium enzymes, and loss of intestinal hormones

4. Hemorrhagic = infectious diarrhea associated with blood in stools

– Example: E. coli O157:H6 infection

5. Altered motility = transit through intestines is too fast for reabsorption of the ~9 L of fluid that enters intestines each day

– Example: dumping syndrome• Typically caused by gastric surgery for peptic ulcers or gastric

bypass surgery• Hypovolemia and hypoglycemia

Pancreatic Conditions• Acute pancreatitis = acute inflammation and destructive

autodigestion of the pancreas– Escape of activated proteolytic enzymes from the ducts– Most common causes in US: gallstones and alcohol– Results in pain, nausea and vomiting, fever, shock, ↑ amylase

and lopase in serum, jaundice, acidosis, hyperkalemia• Chronic pancreatitis = chronic inflammation of the

pancreas leading to fibrosis, calcification, and loss of exocrine function– Most common cause: alcoholism – Can result in pancreatic insufficiency = problems with fat

digestion• Results in steatorrhea (fat in stool) and diarrhea

• Pancreatic cancer– Extremely high mortality rate (95%)– Mostly asymptomatic until disease is advanced– Metastasizes quickly

Cirrhosis

• Covered in TA session

• Chris has posted a review sheet for you to fill in of important GI hormones/ enzymes.

• Good Luck!!