Exam III FGT & Breast Flashcards
The Female Genital Tract (FGT) Definitions
Fundamental reproductive unit = Single ovarian follicle:
- Composed of one germ cell (oocyte)
- Surrounded by endocrine cells
Menarche: Beginning of menstrual cycles
-Avg 11-13 yrs
Female Monthly Sexual Cycle:
-Menstrual cycle controlled by gonadotropins
–Only single ovum is released from ovaries/month
–the uterine endometrium is prepared in for implantation of the fertilized ovum
Ovarian cycle:
- Follicular phase: avg 15 days
- Ovulatory phase: ends with ovulation
- Luteal phase: 13 days
Female Hormonal system
Three Hierarchies of hormones:
-A hypothalamus hormone:
–gonadotropin-releasing hormone (GnRH)
-The anterior pituitary sex hormones:
–follicle-stimulating hormone (FSH)
–Luteinizing hormone
-The ovarian hormones:
–Estrogen and progesterone
Normal Female Sexual Cycle
Plasma concentrations of the hormones:
FSH:
-early follicular maturation
FSH + LH + estrogen:
-late follicular maturation
LF:
-ovulation causes granulosa and theca cells to produce mainly progesterone-> luteal phase
Menarche
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Ovarian & Uterine cycle review
Estrogen-associated clinical Disorders
Endometriosis
A chronic, estrogen-dependent, inflammatory disease
Characterized by: the presence and growth of endometrial tissue outside the uterine cavity
Frequently associated with:
- Moderate to severe back pain
- dysmenorrhea, low back pain, and infertility
The most common anatomic sites: in decreased order of frequency, are the ovaries, anterior and posterior cul-de-sac, broad ligaments
Pathogenesis of Endometriosis
The Pathogenesis is multifactorial:
- Ectopic endometrial tissue
- Inflammation
- Imbalanced cell proliferation and apoptosis
- Angiogenesis
- Genetic factors
Sampson’s theory of retrograde menstruation: endometrial cells flow backward through the fallopian tubes and into the peritoneal cavity during menses
Pre-menarcheal endometriosis: undifferentiated cells of mullerian origin in the peritoneal cavity can differentiate to endometrial tissue
Pathogenesis of Inflammatory Pain in Endometriosis
The Three main players involved in the pathogenesis of endometriotic pain:
- (A) endometriotic lesions
- (B) the innate immune system
- (C) the peripheral nervous system
Mediators released from endometrial lesions directly stimulate sensory nerve endings to generate the nociceptive signal
Activation of the innate immune system releases pro-inflammatory and pro-nociceptive mediators, such as nerve growth factor (NGF) to stimulate sensory nerve endings
Uterine Leiomyomas (Fibroids)
Benign tumors arising from the smooth muscle cells of the myometrium , the most common pelvic tumor in women
Clinical significance: effect the function and structure of the endometrium causing the pathogenesis of excessive bleeding in uterus
Leiomyoma formation:
- transformation of normal myocytes into abnormal myocytes
- growth of abnormal myocytes into clinically apparent tumors
Uterine Leiomyomas Pathogenesis
Genetics:
-multiple different genetic pathways
Steroid hormones: estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli
Stem Cells: play a key role in fibroid pathogenesis
Vascular abnormalities: increased numbers of arterioles and venules, as well as venular dilation
Fibrotic factors:
- an increase in ECM components and collagen
- fibrotic growth factors are also abnormal in leiomyomas
Polycystic Ovarian Syndrome (PCOS)
Fundamentally a disorder of intraovarian androgen excess, closely associated with an insulin resistance
Heterogeneous presentation:
- hirsutism due to the function of hypersecretion of ovarian androgens
- menstrual irregularity and infertility caused by infrequent or absent ovulation
PCOS Etiology
Arises as a congenitally programmed predisposition, first hit that becomes manifest in the presence of a provocative factor, second hit
The congenital factors:
- Hereditary
- Acquired (eg, maternal drugs or nutritional disorders affecting the fetus)
The postnatal provocative factor: usually insulin-resistant hyperinsulinism
Unified Minimal Model of PCOS Pathophysiology
Funtional Ovarian hyperandrogenism (FOH)
Account for the essential clinical features of PCOS
- Hirsutism
- Oligo-anovulation
- Polycystic ovaries
Hyperinsulinism and obesity:
in the ovary, hyperinsulinism upregulates androgen production in theca cells by sensitizing them to LH, and also prematurely lutenizes granulosa cells
LH excess:
The hyperandrogenemia causes secondary LH elevation by interfering with female hormone negative feedback
In the presence of insulin excess, this LH excess aggravates the ovarian dysfunction
Premenstrual Syndrome (PMS) & Premenstrual Dysphoric Disorder (PMDD)
Physical and/or behavioral symptoms in the second half of the menstrual cycle
Physical manifestations:
- abdominal bloating
- breast tenderness
- HA
Risk factors:
- genetic factors
- environmental influences
Pathogenesis:
-Ovarian steroids
–an abnormal neurotransmitter response to normal hormonal changes
-Neurotransmitters:
–the evidence is most supportive for a major role of serotonin in the etiology of PMS
Pathophysiology of Menopause
Processes contribute to the development of menopause:
- hypothalamic and ovarian aging
- environmental, genetic and lifestyle factors
- systemic diseases
Hypothalamic aging leads to desynchronized GnRH production and an abnormal surge of LH.
Anatomy of the Breast
Two major structures:
- ducts
- lobules
Two types of epithelial cells:
- luminal
- Myoepithelial
Two types of stroma:
- interlobular
- intralobular
Breast Lifestyle Changes
Pre-puberty: Lactiferous ducts are formed at birth but lobules remain underdeveloped until puberty.
Puberty: Ovarian estrogen and progesterone induces branching of ductal system and development of lobules
Pregnancy:
- Progesterone and prolactin induce complete maturation of breast at the time of first full-term pregnancy
- Permanent increase in number and size of lobules
- Oxytocin induces myoepithelial proliferation and differentiation
- Following lactation total breast size decreases due to apoptosis of epithelium and lobule atrophy
Aging and menopause:
- Lobular and ductal atrophy occurs
- Interlobular stroma decreases in fibrous connective tissue and increases adipose tissue content
Anatomic Locations of Common Breast Lesions
Classification of Benign Breast Lesions
Non-proliferative:
-Not associated with an increased risk of breast cancer
-Simple breast cyst:
–Fluid-filled masses derived from the terminal duct lobular unit
Proliferative without atypia:
-fibroadenomas
-In certain circumstances: small increased risk of developing breast cancer
Atypical hyperplasia
-substantial increased risk of developing breast cancer (especially multifocal lesions)
–Atypical ductal hyperplasia
–Atypical lobular hyperplasia
Fibroadenoma
SImple fibroadenoma:
Benign solid tumors containing glandular as well as fibrous tissue
Etiology of fibroadenomas is not known
Hormonal relationship likely
For majority, there is no increased risk of developing breast cancer
Complex fibroadenomas:
Associated with a slightly increased risk of cancer with multicentric proliferative changes
Pathophys of Fibroadenoma
Hormonal:
Estrogen, progesterone, and lactation during pregnancy can stimulate fibroadenomas
Some have receptors on their surface and respond to human growth factor (EGH) and growth hormone
Genetics:
Mediator complex subunit 12 (MED12) gene
Estrogen
A Steroid Hormone, derived from the androgenic precursors and androstenedione and testosterone by aromatization
Naturally occurring estrogens are:
17 B-estradiol (E2): primarily produced by theca and granulosa cells of the ovary; it is the predominant form of estrogen found in premenopausal women
Estrone (E1): Is the predominant form of circulating estrogen after menopause
Estriol (E3): is the estrogen the placenta secretes during pregnancy
Estrogen Receptors (ERs)
ER-a is the predominant ER in the uterus, mammary gland
-Sustained estrogenic exposure and activation of ER-a may increase the risk and/or the progression of various cancers, such as breast and endometrium
ER-B is predominantly expressed in ovary and prostate
-In contrast to ER-a, and ER-B activates anti-proliferative and pro-apoptotic pathways in many cancer cells
GPER (G-protein coupled estrogen receptor): mediates rapid estrogen signaling, is expressed in normal ovary and it regulates follicle maturation.
