Hypothalamic-Pituitary- Gonadal Axis

Physiology

What is the process of this? Write it out

KNOW

1. Age and health, enviroment and stress causes

2. Extrahypothalmic central nervous system

3. Hypothalmus

4. Gonadotropin-releasing hormone (GnRH)

5. Anterior pituitary

6. Gonadotropins: follicle-stimulating hormone (FSH) and lutenizing hormone (LH)

7. Sex hormones inhibit Activin Follistatin

And feedback mechanisms return back to the Hypothalamus and Anterior pituitary

Ovary

Physiology

How many ova are present at birth?

How many are present at puberty?

How many mature ones are relased with each cycle?

How many matures over the reproductive years?

-At birth 2 million ova within immature ovarian follicles

- At puberty: 300,000 to 500,000

-Once every mentrual cylcle one (only one) follicle matures and releases an ovum (ovulation)

-400-500 ovarian follicles mature in reproductive years

Follicle Development

Physiology

What do the Gonadotropins do?

-Ovarian Cycle

          -Follicular maturation (Primordial follicle, Primary follicle, Secondary follicle, Grafian follicle)

          -Ovulation

          -Corpus luteum development

          -Corpus luteum degeneration

-Gonadotropins (FSH, LH) and hormones (estrogen and progesterone) regulate ovarian function; abnormal pituitary or thyroid function or reception by target cells can cause dysfunction and infertility ( any problem here and can have problem in any of these areas, pituitary problem can have problems can cause a infertility problem) 

Female Sex Hormones

Physiology and Receptors

1. What secretes female sex hormones?

2. What do they have receptors for?

1. Cells of the stroma, ovarian follicle (granulosa and theca), corpus luteum (CL) secrete female hormones; 2. cells contain receptors for LH and FSH and sex hormones (important for both negative and positve feedback)

Female Sex Hormones

What is the Estrogen Effect, What does estreogen do?

Maturation of reproductive organs, secondary sex characteristics, closure of long bones at puberty, regulation of menstrual cycle, endometrial regeneration after menstruation. ( when think estrogen think endometrium regeneration after menstration)

Female Sex Hormones

Synthesized from cholesterol; steroid

What is the physiology of the developing a follicle?

Estrogen is a streoid. * produces estrogen thorough androgens

1. GnRH stimulates FSH, LH which stimulate ovarian production of estrogens

2. LH also stimulates theca cell production of androstenedione and subsequently converts them to estrogens (E1 & E2); also FSH induces aromatization of androgens and estrogens

3. FSH and estrogen increased FSH receptors in follicle in process of developing dominant follicle

4. Estrone: Androgens converted to estrone (E1) in ovarian and peripheral adipose tissues

How Hormones Are Made in the Body

Start with Cholesterol

Different PATHWAYS See slide 10

1. Cholesterol->Pregnenolone->17, OH, Progesterone-> DHEA->Androstenedfone (can go right to Estrone)->Testosterone->Estradiol(E2)->Estrone (E1)

OR

1Cholesterol->Pregenolone->

Female Sex Hormones

Progesterone

What hormone stimulates ovulation?

What are the progesterone effects?

-LH stimulates ovulation (LH surge occurs when estrogen is at peak level) and secretion of progesterone (via granulosa of dominant follicle)

-Small amounts also secreted by adrenal cortex

-Progesterone Effects: thickens endometrium; secreted from CL/ hormone of pregnancy; maintains thickened endometrium, relax smooth muscle of myometrium, thickens myometrium, prevention of lactation, prevention of maturation of ova by suppressing FSH and LH and thus menstrual cycle (NEGATIVE FEEDBACK)

Female Sex Hormone

Androgens

What is there main control over?

-Androstenedione precursor of female sex hormones

-Contributes to skeletal growth spurt, pubic hair, axillary hair, activates sebaceous glands, role in libido

EXTERNAL STRUCTURE AND FUNCTIONS

Menstrual Cycle

PHASES

MENSTRUATION (MENSES)

Phase 1

functional layer of endometrium disintegrates

(blood mucous, desquamated endometrial tissue)

Estrone

Androgen converted to estrone (E1) in ovarian and peripheral adipose tissue (outside of the ovary)

Most potent; via ovarian follicle and CL (corpus luteum); 95% of circulating E2 via ovary; via estrone and androgens

the dominant follicle in the presence of FSH

Menstrual Cycle

PHASES

Follicular/proliferative phase

PHASE 2

-Number of follicles stimulated to mature

- Anterior pituitary pulsatile secretion of FSH; recruits a dominat ovarian follicle

-FSH responsible for aromatization of androgen to estrogen

-Estrogen and FSH increase FSH receptors on granulosa cells (more sensitive to FSH) and induce LH receptors on granulosa cells (where estrogen is produced)

-LH and FSH together cause more rapid secretion of follicular estrogen (all positive feedback so far)

-As estrogen increases, FSH levels drop resulting in decreased growth of less developed follicles (negative feedback)

-Estrogen causes proliferation of endometrium

-LH causes final follicular growth and ovulation; LH surge results in progesterone production with decreased rate of estrogen secretion

-Final maturation of follicle; increase in stromal tissue in the late phase associated with rise in androgen levels.

Mentrual Cycle PHASES
Luteal/secretory phase

PHASE 3

(know where estrogen and progesterone play a role in all phases)

Luteal = LH secretion-> progesterone secretion from corpus Luteum

-Ovulation marks start of this phase

-Ovarian follicle transforms to CL

-Pulsatile secretion of LH results in progesterone secretion from CL

-In response to progegesterone, glands and blood vessels develop in functional layer and glands secrete thin glycogen containing fluid (secreting)

-With conception: endometrium ready for implantation; without conception: CL disintegrates and ceases production of estrogen and progesterone leading to ischemic portion of the menstral phase (tissue dies, disintegrates and sloughes off)

Menstral Cycle

What does GnRH do?

Menstrual Cycle

What happens during the early follicular phase?

Menstrual Cycle

What happens during the late follicular phase?

Menstrual Cycle

What does LH cause?

mentrual cylcle

What does CL cause?

menstrual cycle

As estrogen and progesterone decline (related to the disintegration of CL) what happens to LH and FSH levels?

Ovary

What are granulosa Cells involved in producing?

Female Sex Hormones

What are the three types of Estrogens and where do they come from?

1. Estrone: Androgens converted to estrone (E1) in ovarian and peripheral adipose tissue.

2. Estradiol: (E2) most potent; via ovarian follicle and CL; 95% of circulating E2 via ovary; via estrone and androgens

3. Estriol:  Peripheral metabolite of estrone and E2 (both)

Hormonal Control of Menstrual Cycle

What does "Activin" do?

-Stimulates the secretion of FSH and increases the pituitary response to GnRH

-Increases FSH binding in granulosa cells of the dominant follicle

Hormonal Control of Menstrual Cycle

What does "Inhibin" do?

It is stimulated by FSH and it, in turn, supressess FSH synthesis (cycle would never happen without it)

Hormonal Control of Menstrual Cycle

What does "Follistatin" do?

-Produced in the pituitary gland and found in the follicles

-Suppressess FSH activity by binding to activin (suppresses activin and boosts inhibin)

Structure and Function of the Breast

What is the breast made up of?

-Modified sebaceous glands

-15-20 pyramid shaped lobes seperated and supported by Cooper ligaments; each lobe with 20-40 lobules subdivided into glandular alveoli; alveoli composed of secretory acini that synthesize milk; alveoli empty into lactiferous ducts

Structure and Funciton of the Breast

What happens to the breast during the follicular/proliferation phase of mentration?

Progesterone levels influence growth of the alveoli and increase and contribute to actions of estrogen

Structure and Funciton of the Breast

What happens to the breast during the luteal/ secretory phase of menstruation

-Progesterone levels influence growth of the alveoli and increase and contribute to the actions of estrogen.

-Specific effects of estrogen and progesterone: dilation of ducts, conversion of alveolar cells to secretory cells; fluid secretion, mitotic activity, DNA production in non gladular tissue and  glandular epithelium.

Structure and Function of the Breast

What occurs in the surrounding tissue?

-Lymphatic drainage primarily through axillary nodes.

- Extensive capillary network surrounds alveoli supplied by internal mammary artery

- Receive Sensory innervation from branches of the 2-6 intercostal nerves; acocunts for referral of breast pain to chest, back, scapula, medial arm and neck.

2-8 years before, erratic and high levels of estrogen (symptoms), mentrual cycles shorten/irregular; anovulation

(estrogen low, FSH high) levels of sex hormones decreases; reproductive organs atrophy, vaginal epithelium thins, glandular secretions diminsh; elevated FSH and LH. 

Male Reproducitve System

External Genitalia

Testes

-Essential organs for reproduction

-Produce gaetes

-Produce Sex hormones (androgens and testosterone)

-Suspended outside the pelvic cavity (sperm production requires an enviroment that is 1 percent or 2 percent C cooler than body temperature

Male Reproducitve System

External Genitalia

Epididymis

-When sperm enter, not mature, motile or able to fertilize

-Takes 12 days to travel the length of the epididymis, receive nutrients and testosterone to enhance maturity and ability to fertilize

-Continuous with vas deferans; muscular and peristatic action to transport sperm towards urethra

Male Reproducitve System

External Genitalia

Scrotum

Houses the testes, epidiymis, spermatic chord

Penis

Male Reproductive System

Internal genitalia

SEMINAL VESICLES

-provide fructose as an energy source and secrete prostaglandins that promote smooth muscle contraction to assist in transport

-Then goes to Ejaculatory duct

Male Reproductive System

Internal genitalia

PROSTATE GLAND

-After going through ejaculatory duct it goes to Prostate gland

- this contracts rythmically and secretes prostatic fluid; alkaline pH helps sperm survive in acidic environment of female tract; clotting enzymes and fibrinolysin helps mobilize sperm

Male Reproductive System

Internal genitalia

Bulbourethral glands

Secretes mucus into urethra

1. Spermatogonia (mitosis)

2. Primary spermatocytes (Meiosis I)

3. Secondary spermatocytes (Meiosis II)

4. Spermatids (differentiate into spermatozoa)

5. Sertoli cells ( nutrients and hormonal signals for support of spermatids)

(not motile or serilize,  have to mature in the epididimysis) (Unlike the female, they complete meiosis II before being released, In the ovary the ova is released from the ovary before completing meiosis II)

Male Sex Hormones

Androgens---> Testosterone

-Primary androgens is testosterone

-Produced mainly in Leydig cells of the testes; some from the adrenals

-Testosterone: fetal differentiation; Urogenital system development; Sex organ growth and secondary sex characteristics; Nervous and skeletal tissue development; sex drive.

Male Sex Hormones

Where are hormones secreted?

At the level od the hypothalamic-pituitary -testicular (H-P-T) axis

- At the testes, pituitary and hypothalamus.

Male Sex Hormones

How do they control and coordinate testicular function?

Male Sex Hormones

Positive- Negative Feedback system of the H-P-T- Axis

1. NT regulates Gn RH synthesis and release (NE stimulates; SE and DA inhibit)

2. GnRH stimulates LH and FSH acts on Leydig cells to regulate testosterone secretion; FSH acts on seminiferous tubules to promote spermatogenesis.

3. Inhibin inhibits pituitary FSH and thus proliferation of spermatogonia BUT fascilitates LH stimulation of androgens biosynthesis in Leydig cells

4. Sex steroids inhibit hypothalamic GnRH secretion and pituitary LH responsiveness to GnRH

5. Any disruption along the H-P-T axis may lead to hypogonadism or infertility

* 98% of testosterone bound to sex hormone binding globulin

*Testes secrete 25 % estrogen with the majority converted to estrogen from testosterone and androstenione.

FEMALE
Hormonal and Menstrual Alterations

PRIMARY DYSMENNORRHEA

Mechanism of Action and Clinical Manifestations

-50-90% of young women

-Painful menstruation associated with prostaglandin (PAIN) release in ovulatory cycles; NOT with pelvic disease

- Related to duration and amount of menstrual flow

FEMALE
Hormonal and Menstrual Alterations

PRIMARY DYSMENNORRHEA

pathophysiology

-Effects of excess endometrial prostaglandin production enhanced by progesterone; secretory endometrium; first 48 hours of menstruation

-10x as much prostaglandin F (PGFalpha2)- potent myometrial stimulant and vasoconstrictor

-Those that are annovulatory (on birth control) do not have dysmenorhhea--> if you don't ovulate, you don't produce a corpus luteum (don't have progesterone that produces prostaglandins)

FEMALE
Hormonal and Menstrual Alterations

SECONDARY DYSMENNORRHEA

clinical manifestations, patho and mech of action

-Painful menstruation RELATED to pelvic pathology (endometriosis, pelvic adhesions, inflammation, uterine fibroids, polyps, tumors, cysts, IUDs)

-Can occur at any time in the menstrual cycle (quesitons can weed out when did it happen)

Female

Hormonal and Menstrual Alterations

Primary Amenorrhea

pathophysiology

4 Levels

1. Hypothamamic Disorders: no synthesis of GnRH and thus no production of LH and FSH; no signals to ovary for ovarian and endometrial changes; ovarian hormones absent and estrogen-dependent sex characteristics absent; may be congenital or acquired.

2. Anterior pituitary disorders: congenital or acquired; hydrocephalus or other space occupying lesions; if lesions develop before conclusion of pubery may have some secondary sex characteristics.

3. Ovarian disorders: Gonadal dysgenesis (Turner's Syndrome 45, X; no homologous X or Y chromosome), ovaries lack gametes and ovarian failure is complete; no follicular development or estrogen production; no secondary sex characteristics; high levels of FSH, LH. Androgen insensitivity syndrome (testiclar feminizing syndrome) male genetically an female morphologically; gonads in the abdomen that produce androgens and estrogens; no androgen receptors but have estrogen receptors; have female external genitalia but no internal genitalia; have female sex characteristics.

4. Anatomic disorders of the outflow tract: congenital absense of a vagina and uterus, congenital uterine hypoplasia (immature type of organ); can have normal ovarian funciton with normal skeletal growth and secondary sex characteristics; no menstruation.

Female

Hormonal and Menstrual Alterations

Primary Amenorrhea

Mechinism of Action

Failure of menarche and the absence of menstruation by age 14 years without the development of secondary sex characteristics OR by age 16 years regardless of the presence of secondary sex characteristics.

Female

Hormonal and Menstrual Alterations

Secondary amenorrhea

Mechanism of Action

Absense of menstruation for a time equivalent to three or more cycles or 6 months in women who have previously menstruated

-Causes: Disease (most often hypothyroidism, hyperprolactinemia, PCOS, HPO interruption secondary to excessive exercise, stress, weight loss)

-Common during early adolescence, perimenopause, pregnancy and lactation

Female

Hormonal and Menstrual Alterations

Secondary amenorrhea

Pathophysiology

-Structural abnormalities (removal of the uterus)

-Elevated ovarian steroid hormone levels which inhibits ovulation (anovulation)

-Depressed ovarian steriod levels

-Increased prolactin, decreased gonadotropins (LH and FSH), irregular secretion of gonadotropins, low CNS NT (dopamine)- anything that alters the feedback mechanisms that ovarian hormones have on the hypothalamus and pituitary

-Hypothyroidism: increased TRH from hypothalamus; TRH binds not only to anterior pituitary thyrotropes but also lactotrophs which increase PRL secretion

-Hyperprolactinemia: evelate PRL increase dopaimine (DA) which decreases GnRH secretion and thus LH and FSH (gonadotropins)

Female

Hormonal and Menstrual Alterations

Secondary amenorrhea

Clinical Manifestations

Infertility, vasomotor flushes, vaginal atrophy, acne, osteopenia, hirsutism

Hormonal and Menstrual Alterations

Abnormal Uterine Bleeding

Menstrual irregularity/abnormal bleeding patterns:

-polymenorrhea, oligomenorrhea, metrorrhagia, hypermenorrhea, menorrhea, menorrhagia, menometrorrhagia (page 823, definitions)

-anovulatory cycles (failure to ovulate) most common cause of cycle irregularity

-Other causes are tumors, polyps cysts

- Common causes of age group (trauma, PID, oral and IUD contraceptives, PCOS, malignancy, endometriosis, thyroid disease, liver disease, DM, obesity, HTN)

Hormonal and Menstrual Alterations

Abnormal Uterine Bleeding

Dysfunctional Uterine Bleeding

Definition: heavy or irregular bleeding without disease; diagnosed once other causes excluded

-Perimenopausal women most affected; progesterone secretion is absent but estrogen still continues to be secreted (levels high and erratic); in the absense of growth limiting progesterone and periodic desquamation, endometrium hypervascular and hyperglandular but without support matrix; flow irregular and excessive or both from random breakdown of tissue; unopposed estrogen causes proliferation, hyperplasia, and can lead to atypia and carcinoma

Hormonal and Menstrual Alterations

Polycystic Ovary Syndrome

A woman must have two of these to have it, what are the three?

1.  Oligo-ovulation or annovulation

2. Elevated levels of androgens or clinical signs of hyperandrogenism

3. Polycystic ovaries.

Hormonal and Menstrual Alterations

Polycystic Ovary Syndrome

Mechanism of Aciton

-Leading cause of infertility in the US; most common endocrine disturbances

-Genetic basis (mutations in genes for the following functions: steroid biosynthesis, androgen biosynthesis, insulin receptors in the ovary)

-Hyperandrogenic state, glucose intolerance/IR/hyperinsullinemia

-Obesity add/worsens (signals increase cholesterol level, BP, decrease skeletal muscle ability to take up glucose, etc.)

-Characterized by excessive production of both androgens and estrogen

Hormonal and Menstrual Alterations

Polycystic Ovary Syndrome

Clinical Manifestations

anovulation, infertility, dysfunctional bleeding or amenorrhea, hirsuitism, acne, obesity; with late manifestations of dyslipidemia, T2DM, CVD, endometrial hyperplasia and carcinoma; at rish for gestational diabetes, pregnancy induced HTN, preterm birth and perinatal mortality

Hormonal and Menstrual Alterations

Polycystic Ovary Syndrome

Pathophysiology

-Hyperinsulinism and IR-ovary more susceptible to insulin; insulin stimulates androgen secretion which decreases SHBP resulting in increased testosterone levels

-Dysfunction of follicle development via insulin and androgens; inappropriate pulsitile LH (elevated) and FSH (low) triggers a cycle that perpetuates oligo-annovulation

         : FSH not totally depressed so continue to stimulate follicle growth but not to maturation

         :LH increased through increased GnRH, results in increased androgens (adrenal and ovaries), androgens converted to estrogen, testosterone decreases SHBG which increases estrogen which positively feeds back to LH and negatively to FSH

         :Testosterone produces premature follicular failure and annovulation

Hormonal and Menstrual Alterations

Premenstrual Syndrome (PMS) and Premenstrual dysphoric disorder (PMDD)

-Cyclic physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usualy activities

-Occurs in the luteal (postovulatory) phase

-Abnormal nervous, immunologic, vascular, and GI tissue response to the normal menstrual cycle (>200 symptoms); symptoms triggered by preovulatory estrogen peak or post ovulatory progesterone or both

-GABA and noradrenaline may be modulatorys and are known to interact with estrogen and progesterone; also have mood and behavior effects (negative mood, irritability, aggresion, impulse control)

-Sex steroids interact with RAAS (Renin-angiotensin system) explaining water retention, bloating and weight gain.

Female

Infection and Inflammation

PELVIC INFLAMMATORY DISEASE (PID)

Mechanism Of Action

-Acute inflammation caused by infection

-May involve any organ of reproductive tract: uterus, fallopian tubes, ovaries and sometimes entire peritoneal cavity: Salpingitis (fallopian tubes) Oophoritis (ovaries)

-Sexually transmitted disease migrate from the vagina to the upper genital tract

Female

Infection and Inflammation

PELVIC INFLAMMATORY DISEASE (PID)

pathophysiology

-Polymicrobial infection; gonorrhea, chamydia contribute but 80% mixed nongonococcal/nonchlamydial

-Microbes ascend from infected cervix to enfometrial tissue; infect uterus and adnexae; INFLAMMATORY RESPONSE leasing to tubonecorsis (tissue death) with repeated infections

-After one episode, 15-25% developing long term sequelae (infertility, ectopic pregnancy, chronic pelvic pain, dyspareunia, pelvic adhesions, perihepatitis, tubo-ovarian abscess)

Female

Infection and Inflammation

PELVIC INFLAMMATORY DISEASE (PID)

Clinical Manifestations

sudden severe pain with fever to no symptoms; asymptomatic cervicitis may be present for some time before PID develops; low bilateral abdominal pain (dull gradual onset) with pain worsening with activity/ sex; difficult or painful urination and irregular bleeding

Female

Infection and Inflammation

Vaginitis

-Infection of the vagina

-Sexually transmitted pathogens and Candida albicans

-Acidic nature of vagina provides some protection: maintained by cervical secretions, normal flora; altered pH caused by douching, spermacides, sprays, deodorants, tampons. Altered glycogen (pregnancy or diabetes, increased glucose)

-discharge: malodorous, copious, irritating

Female

Infection and Inflammation

Cervicitis

-inflammation or infection of the cervix

-Mucopurulen cervicitis (MPC), caused by sexually transmitted disease

-Detect with Pap smear

Female

Infection and Inflammation

Bartholinitis

-Inflammation of one or both ducts that lead from the vaginal opening to Bartholin glands

-Caused by microorganisms that infect the lower female reproductive tract.

-Inflammation narrow the distal portion of the ducts

-Leads to obstruction and stasis of glandular secretions

Female

Infection and Inflammation

Vulvitis

-inflammation of the female external genitalia

-difficult to evaluate and treat (mechnisms poorly understood): contact with soaps, detergents, lotions, hygienic sprays, shaving, menstrual pads, perfumed toilet paper, or nonabsorbing or tight fitting clothing

-Abnormalities in vestibular mucosa, pelvic floor musculature, CNS pain regulatory pathways

-May be caused by vaginal infections that spread to the labia

-May result from other skin disease that can involve the vulva. (excema) hard to treat

Benign growths and Proliferative Conditions

Leiomyomas

What are they commonly called?

What are they?

How may women do they affect?

What is the pathology?

Clinical menifestations

-Commonly called uterine fibroids

-Benign tumors of smooth muscle cells

-Affect 70-80% of women; most small, benign, asymptomatic and insignificant; prevelance increases with age. The bigger/increased amount more of a problem

-Unknown pathology; may be related to estrogen and progesterone, growth factors, angiogenesis and apoptosis; estrogen and progesterone sensitive

-Cause abnormal uterine bleeding, pain and symptoms related to pressure on nearby structures.

Benign Growth and Proliferative Conditions

Endometriosis

-Functioning endometrial tissue or implants ouside the uterus (pelvic and abdominal cavities) CHRONIC

-Responds to hormone fluctuations of the menstrual cycle; extopic endometrium proliferates, breaks down and bleeds

- Possible causes: Retrograde menstruation (menstrual fluids move through fallopian tubes into the pelvic cavity, The tissue responds to hormones just as it would if it were inside the uterus à sloughing off can then occur in abdominal cavity, bladder, etc. (wherever the tissue is present) (RETROGRADE MENSTRUATION)

); Spread through vascular and lymphatic systems; Stimulation of multipotential epithelial cells on reproductive organs

-Depressed Tc and NK cells tolerate ectopic tissue

-Macrophages stimulate endometrial cell proliferation outside the uterus

-Autoimmune response ( Develop an immune response against self)

-bleeding causes inflammation, triggering a cascade of cellular inflammatory mediators (cytokines, chemokines, GF); inflammation leads to fibrosis, scarring and adhesions

Disorders of the Scrotum

VARICOCELE

What will a patient present with?

What causes it?

What can it result in if not treated?

-Inflammation/dilation of veins in spermatic cord; "bag of worms"; painful; primarily the left side

-Causes: inadequate or absent valves in the spermatic veins; permits blood to pool in veins rather than into venous system; decreses blood flow into testes and decreases spermatogenesis; infertility

-Can ligate spermatic vein or occlude vein to repaid; scrotal support may be sufficient

-Sudden development is a late sign of a renal tumor.

Disorders of the Scrotum

HYDROCELE

What is it the most common cause of?

-Scrotal swelling due to collection of fluid within the tunica vaginalis

-Most common cause of scrotal swelling

-6% in male newborns and are congenital

-In adults, imbalance between fluid secretion and resorption of tunica vaginalis

-Compression of testicular blood flow may lead to atrophy

-Can be idiopathic; can also result from trauma, infection or tumor.

-Remove hydroveal and prevent recurrence by sclerosing or exercing the tunica vaginalis

-PAINLESS; extratesticular and transilluminated

Disorders of the Scrotum

SPERMATOCELE

-Painless divertiuculum of the epididymis located between the head of the epididymis and the testes; efferent ducts of the epididymis with cystic dilation but does not communicate with the epididymis.

-Contains milky fluid that contains sperm and does not cover the entire anterior scrotal surface (compared with hydrocele; clear yellow fluid affects the entire scrotum)

-Freely mobile mass distinct from the testes and may be transiluminated

Disorders of the Testis

TORSION OF THE TESTIS

-Rotation of the testis

-The rotation causes the twisting of the blood vessels in the permatic cord; reducing or stopping blood flow to the testes

-PAINFUL and swollen testis

-Condition may be spontaneous or follow physical trauma

-Surgical emergency within 6 hours

- Negative phren sign

Disorders of the Testis

ORCHITIS

What is the most common cause?

What may be a result of this?

-Acute inflammation of the testis

-Complication of a systemic disease related to epididymitis; mumps most common infectious cause

-Sudden onset with fever, edema, and tenderness; acute hydrocoele may develop

-Atrophy with irreversible damage to spermatogenesis may result; may cause infertility.

Disorders of the Testis

Cancer of the Testis

What age group is this most common in?

- Among the most curable of cancers

-Common in men between ages 15 and 35

-Causes painless testicular enlargement

-Pathogenesis:

:Germ cell tumors arising from male gametes; comstitute 90%

:Two types: seminomas (most common, least aggresive) and nonseminomas (rare, most addressive)

:tumor named for cellular origin; Leydig cell, Sertoli Cell, granulosa cell, theca cell

:Genetic predisposition

Disorders of the Epididymis

EPIDIDYMITIS

what is it?

What can it be a result of?

-Inflammation of the epididymis

-The pathogenic microorganism reaches the epididymis by ascending the vas deferens from an already infected bladder or urethra

-Can result from reflux of sterile urine into ejactalotory ducts (chemical epididymitis) with heavy lifting or straining

Disorders of the Prostate Gland

Benign Prostatic Hyperplasia

Mechanism of Action

-Enlargement of the prostate gland; hyperplasia

-Symptoms associated with urethral compression

-Relationship to aging

Disorders of the Prostate Gland

Benign Prostatic Hyperplasia

Pathophysiology

-Aging and circulatory androgens disrpt the balance of GF signaling pathways and stromal/epithelial interactions to create a growth promoting and tissue remodeling environment

-Levels and ratios of endocrine factors (androgens, estrogens, gonadotropins and prolactin) and balance between growth stimulatory/inhibitory factors (IGF, EGF, NGF, IGF, binding protein, TGFbeta) lead to increased prostate volume; increased oxygen demand causes local hypoxia which induces angiogenesis

Disorders of the Prostate Gland

Benign Prostatic Hyperplasia

Clinical manifestations

-Early obstructive symptoms (weak prolonged voiding, straining, hesistancy, intermittance) and irrative symptoms (nocturia, urgency, incontinence, bladder pain and dysuria, dettussor muscle hypertrophies to force urine out of the bladder.

-Late: bladder unable to empty via detrissor muscle decompensation, urine retained in bladder, decreases urine stream, bladder distention

Disorders of the Prostate Gland

Benign Prostatic Hyperplasia

Medications

-alpha adrenergic blocjers (prazosin and tamisulosin; relax smooth muscles in prostate and urethra); anti androgens agents (finasteride: slectivly clock androgens at the prostate and cause prostate shrinkage)

Disorders of the Prostate Gland

Benign Prostatic Hyperplasia

Evlaluation

Digital Rectal exams, Prostate-specific antigen (PSA) monitoring

Disorders of the Prostate Gland

Prostatitis

- Inflammation of the prostate: some degree of inflammation present in 4-36% of men

-Normal protective barriers are not protective: Mechanical: Urethral length, micturition and ejeculation

Chemical: antimicrobial

-Similar Symptoms to BPH

Types: 1. Acute Bacterial: sudden onset, malaise, fever chills, dysuria; usually associated with acute bladder infection; 2. Chronic bacterial: often caused by prostatic calculi; source of bacterial persistence and relapsing infections. 3. Nonbacterial: inflammation without bacterial infection; most common.

Clinical Manifestations: Very painful, ill-appearing

Disorders of the Prostate Gland

Prostate Cancer

Mechanism of Action

-Most common male cancer

-95% of prostate neoplasma are adenocarcinomas and demonstrate peripheral zone growth

-Prostatic cancer is asymptomatic until its advanced stages

-Symptoms are similar to BPH through symptoms of obstruction are progressive and do not remit

Disorders of the Prostate Gland

Prostate Cancer

Risk Factors for Prostate Cancer

-Dietary factors: high fat may increase risk; diet with vegetables, soy, vitamin D, calcium, fiber, folic acid may reduce risk.

-Hormones: develops in an androgen dependent epithelium and is androgen sensitive; no clear patterns associated with circulating hormones with cancer risk

-Vasectomy

-Familial factors: strong familial predisposition may be responsible for 5-10% of cases; one first degree relative 2x the risk; 2 first degree relatives 5x the risk; also mutations in multiple tumor suppressor genes suspected (GST-P1, PTEN, RB, p16/INK4a, MLH1, MSH21, APC)

Disorders of the Prostate Gland

Prostate Cancer

General Hypothesis of Pathogenesis

-Androgens acts as tumor promotors through Androgen-recepor mediated mechanisms

-Enhanced carcinogenetic activity of strong endogenous DNA toxic carcinogen (reactive estrogen metabolites, estrogen and protatic generate ROS)

-Alterations in autocrine/paracrine growth, stimulating and growth inhibiting factors

-Unknown Enviromental/ Lifestyle carcinogens.

Prostate Cancer

What are th most common sites for distant metastasis?

-Lymph nodes

-Bones

-Liver

-Adrenals