Hypothalamic hypophysial-gonadal axis

• hypothalamic hormone is GnRH(gonadotropin releasing hormone)
• anterior pituitary hormones are FSH and LH
• FSH stimulates gametogenesis and LH stimulates sex hormone synthesis and secretion

Spermatogenesis overview

• conversion of primitive germ cells(spermatogonia) lining the seminiferous tubules into spermatozoa (takes 64 days and several hundred million a day)
• spermatogonia divide into primary spermatocytes and then divide(meiosis to become secondary spermatocytes
• these become spermatids and then differentiate into spermatozoa
• mature in the epididymis and most stored in the vas deferens

Roles of sertoli cells and accessory glands

• provide protection, nutrition and mechanical support to developing sperm
• secrete fluid to bathe and transport sperm
• secrete androgen binding protein and inhibin(inhibits FSH secretion)
• prostate, bulbourethral glands, and seminal vesicles secrete fluids for suspension and survival of spermatozoa during ejaculation(pH=7.5)

Endocrine control of spermatogenesis

• FSH stimulates seminiferous tubules and sertoli cells(via cAMP) to drive spermatogenesis(play essential role
• LH(ICSH) acts on the interstitial eydig cells(via cAMP) to stimulate synthesis/secretion of androgens
• testosterone(androgen) is crucial to spermatogenesis(sterile with out it) 
• nutritional status and body temperature also influence

Androgens

• are the masculine sex steroid hromones, produced primarily by the interstitial(leydig) cells of the testes
• pergnolone(from cholesterol) is precursor for all steroid hormones
• androgens also made by the adrenal cortex, ovary and placenta
• testes(and adrenals) also produce minor amounts of estrogen by aromatase conversion of testosterone
• testosterone in plasma(98%) circulates bound primarily to testosterone binding protein(TBG)

Androgen Actions

• widespread physiological effecs on reproductive organs, secondary sexual characteristics, behavior (libido), as well as non repro effects(growth, protein anabolism)

Dihydrotestosterone(DHT)

• peripheral conversion of testosterone via 5alpha-reductase yields DHT
• DHT mediates many of the reproductive effects of androgens

Feedback regulation of 

Hypothalamic-hypophysial-testicular axis

• testosterone inhibits both the pituitary and hypothalmus from secreting more LH or GnRH
• FSH creates inhibin that then goes on to inhibit FSH secretion and GnRH(indirect)

Klinefelters syndrome

• decreased leydig cell function
• results in eunuchoidism(elevated FSH/LH)
• XXY genotype

Kallmans/Frohlichs syndrome

• hypogonadotropic eunuchoidism
• lack of GnRH, thus FSH/LH, testosterone, sexual development all absent
• Xlinked disorder

Testicular Feminization

• heriditary disorder
• absence of testosterone receptors
• results in male genotype, female phenotype(including geenitalia and female sexual development)

Hypergonadism

• usually very rare
• precocoius puberty: brain tumors alter normal gonadostat function, resulting in early sexual development; also can be of idipathic(unknown) cause
• Pseudoprecocious puberty: most common cause is form of congenital adrenal hyperplasia, which shunts adrenal steroid synthesis into androgen pathway(may also occur due to ectopic LH producing tumor)

Corpus Luteum

• second endocrine organ of the ovary(progesterone if ovum fertilized)
• CL differentiates from the collapsed wall of the ruptured follicle after ovulation(corpus hemmorhagium)
• formed by the granulosa and thecal cells, which proliferate and form a mass of yellowish luteal cells
• functional for about 11 days then degenerates to the corpus albicans
• if pregnancy occurs, cL remains functional for several months as an endocrine gland to maintain pregnancy(ceases menstrual cycle)

Aromatase

• converts either androstenedione to estrone or 
• testosterone to estradiol 
• these converted to estrogen
• testosterone made in theca cells than transfered to Granulosa where FSH helps drive it to estrogen where it either stays in the granulosa or goes off to make secondary sex characteristics

Ovarian Cycle

• estrogen spikes(LH surge) just before ovulation/leads to ovulation
• corpus luteum causes spike in progesterone (also allows for elevated estrogen levels)
• if no hCG becomes present(fertilization) then CL involutes (c albicans) and dies
• when estrogen and progesterone levels drop low menstruation happens
• LH surge is thought to be from increased sensitivity of gonadotrophs to GnRH

Feedback regulation by 

E2 and Progesterone

• normally progesterone inhibits hypothalamus and estradiol inhibits anterior pituitary
• this is called tonic negative feedback
• in late follicular phase: switch to positive feed back where high E2 stimulates hypothalamus and ant pituitary to promote LH surge

Estrogen Reproductive Effects

• oviducts: increase in cilia formation and acitivty in lining and increased muscular wall contractility
• uterus: increased endom proliferation, myometrium growth and watery secretion from cervical glands
• Vagina: increased epithelial proliferationa nd glycogen deposition

Progesterone

• oviducts: increase in lining secretion and decrease in contractility
• uterus: increase in differentiationa nd secretion of endometrium, decrease in myometrium contractility and cervical glands release dense, viscous secretion
• Vagina: increase in differentiation and decrease in proliferation

Relaxin

• secreted by corpus luteum during pregnancy
• softens(ripens) the cervix and pelvic ligaments prior to birth
• aids in fetal expulsion

Menopause in the Female

• age 45-50 years the menstrual cycle becomes irregular and eventually ceases
• apparent cause is depletion of the ovarian follicle pool. ovulation and menses ceases first, followed by the gradual decline of estrogen 
• affects estrogen dependent targets and negative feedback loops
• physiological changes: uterus structure/function; increased body temperature, decreased bone density and psychological stress
• estrogen replacement therapy is effective but may increase risk fo endometrial and breast cancers and have vascular or gallbladder diseases

Infertility

• about 1 out of every 6-8 couples infertile(60% female)
• failure to ovulate: may arise form a hyposecretory defect or an abnormality of the ovary
• endometriosis: abnormal growth of tissue outside of the uterus which often leads abnormal uterine contractions and fibrosis(both inhibit implant)
• salpingitis: inflamation of fallopian tubes leading to fibrosis and blockagee
• abnormal cervical mucous: thickened mucous inhibits sperm transport

Primary Amenorrhea

• ovarian hypofunction
• failure of menstrual cycle development
• relatively uncommon(developmental abnormality in the ovary)
• common symptoms of ! ammenorhea are absence of estrogen excretion and secondary sexual characteristics(elevated FSH/LH)
• another common cause is a deficit in gonadotropin secretion(kallmans syndrome) or panhypopituitarism

Secondary Amenorrhea

• ovarian hypofunction
• loss of normal menstrual cycle in previously cycling women(much more common then primary)
• most common cause is prolactin-secreting adenoma in the adenohypophysis(inhibits FSH/LH). although many other causes exist
• this and primary can cause female eunuchoid characteristics(icnreased height, small genitalia, and lack of 2ndary charc

Ovarian Hyperfunction

• farily rare since elevated levels of estrogen will feedback supress GnRh and LH/FSH secretion
• before puberty, early development of sec sex charc may occur with or without menstrual cycling and cause
• true precocious puberty: early release of GnRH results in early maturation(usually idiopathic, unk)
• pseudoprecocious puberty: increased ovarian steroid production in absence of gonadotropin release or ovulations
• after puberty, hypergonadism in the adult usually arises from an estrogen secreting tumor(ovarian granulosa tumor)

Sperm Transport and Capacitation

• transport from uterus to the fallopian tubes is promoted by estrogen
• beating cilia-fluid currets in cervix and ampulla of uterus
• production of clear, watery cervical mucus
• contraction of uterine smooth muscle(cervix and ampulla)
• swimming action of sperm(not estrogen dependent
• female reproduct tract plays critical role in allowing sperm to fertilize ovum(capacitation)

Steps in Fertilization of Ovum

• sperm penetration-enzymes in sperm head facilitate penetration
• fusion of plasma membranes-sperm enters cytoplasm
• ovum completes meiosis and excludes second polar body
• fusion of nuclei-first mitotic division of new embryo
• fertilized ovum(zygote) travels 3-4 days prior to implantation; if the ovum is not fertilized, it disintegrates and is phagocytized
• rarely, a zygote may remain in the fallopian tube(tubal pregnancy) or more rarely; zygote may be expelled into abdominal cavity(ectopic pregnancy); both corrected by surgery 

Implantation of blastocyst

• digestion of endometrium and migration into decidua
• vili development and vascularization
• decidua provides nourishment for first 8 wks
• progesterone plays a role in uterine relaxation
• hCG levels detectable 3-4 days after implantation

Human Chorionic Gonadotropin

• maintains early pregnancy and the CL
• hGC stimulates male fetus to secrete testosterone for male sex organ development

Progesterone during pregnancy

• ovarian progesterone predominates early in pregnancy, placental progesterone secretion increases during the 2nd and 3rd trimesters
• progesterone acts locally on endometrium/myometrium and systemically on the breasts(to prepare for lactation)

Estrogen and Pregnancy

• placenta secretes secretes estrogen during the latter half of pregnancy to promote enlargement of uterus, breasts, external genatalia and to relax pelvic ligaments
• placenta lacks the enzymes to convert pregnolone to DHEA and thus, cannot synthesize estrogen directly
• placenta depends on the fetal zone of the fetal adrenal gland to convert pregnalone to DHEA
• DHEA travels to the placenta for syn of estriol (feto-placental unit)

Human Placental Lactogen

(hPL)

• produced by the placenta at about the 5th wk of pregnancy
• functions still not clear but may be:
• breast development and lactation
• generalized growth effects(possibly synergistically with GH)
• glucose sparing effect for fetus(at moms expense) via decrease in maternal insulin sensitivity

Regulation of Parturition

• human pregnancy averages 270 days
• factors that trigger parturition are not completely understode but hromones from fetus, placenta, and mother play key roles
• initiation of labor: number or sens of myometrial progesterone rec, increase in the estrogen:progesterone ration, oxytocin released by posterior pituitary in response to myometrial stretch

Stages of labor

• dilation of cervix: longest period(6-24 hr with first pregnancy, usually less with subsequent ones)
• delivery of fetus: a neural reflex triggers contraction of abdominal and uterine muscles, expelling fetus
• expulsion of the placenta: continued uterine contractions separate the placenta from the uterine wall and deliver it

Mammogenesis

• breast development
• estrogen and prog(primary) stimulate marked growth of the breast tissue during puberty(proliferation of gland issue and adipose deposits)
• insulin, cortisol, and thyroid hromones play permissive roles
• during pregnancy, further breast development is stimulated by ovarian steroids, prolactin and hPL. these are needed for full development of ductal and alveolar structures

Lactogenesis

• initiation of milk production
• prolactin is the single most important hormone regulating milk production
• lactogenesis and secretion of milk do not occur until after parturition since estrogen and progesterone supress prolactin(E and P drop immediatly after birth)

Lactopoiesis

• maintenance of milk production
• continued production of milk depends upon continued prolactin secretion, which depends upon frequent nursing (physical stimulation)
• adequae nutrition, water, and mineral balance(calcium) necessary, along with the metabolic hormones

Milk ejection or Letdown

• regulated by a neuroendocrine reflex arc
• higher brain centers can influence this reflex arc(stress inhibits, auditory, visual cues stimulate)
• lactation suppresses ovarian functino(can cause amenorrhea), which may function to inhibit ovulation (not full proof)

Definition of shock

• Shock results from inadequate perfusion of the body's cells with oxygenated blood
• the definition of shock does not involve low blood pressure, rapid pulse or cool clammy skin-these are merely the signs

Causes of hypovolemic shock

• Hypovolemic shock refers to a medical or surgical condition in which rapid fluid loss results in multiple organ failure due to inadequate perfusion
• hemorrhage : body responds by activating and involving nearly every physiological system: hematologic, cardiovascular, renal, neural (ADH, renin), endocrine(ADH, R-A-A), pulmonary(hyperventilation), GI(water reabs and less secretion)
• burns, diarrhea, vomiting, peritonitis

Hypovolemic Shock: Hematologic System

• activating the coagulation cascade and contracting the bleeding vessels(via local thromboxane A2 release)
• Platelets are activated which form an immature clot on the bleeding source
• damaged vessel exposes collagen, which subsequently causes fibrin deposition and stabilization of the clot

Hypovolemic Shock: Cardiovascular System

• increases the heart rate, increasing myocardial contractility, and constricting peripheral blood vessels
• this response occurs secondary to an increase in release of norepinephrine and a decrease in baseline vagal tone(regulated by the baroreceptors in the carotid arch, aortic arch, left atrium and pulmonary vessels)
• cardiovascular system also responds by redistributing blood to the brain, heart, and kidneys and away from skin, muscle, and GI tract 
• pale appearance from tremendous cutaneous vasoconstriction

Hypovolemic Shock: Renal System

• the kidneys respond to hemmorhagic shock by stimulating an increase in renin secretion from the juxtaglomerular apparatus
• Angiotensin II has 2 main effects, vasoconstriction of arteriolar smooth muscle and stimulation of aldosterone secretion by the adrenal cortex

Hypovolemic Shock: Neuroendocrine System

• causes an increase in circulating antidiuretic hormone(ADH)
• ADH is released from the posterior pituitary gland in response to a decrease in blood pressure(as detected by baroreceptors) and a decrease in sodium concentration
• ADH indirectly leads to an increase in reabs of water and salt(NaCl) by the distal tubule, the collecting ducts and the loops of henle

Types of Vasogenic

• psychogenic
• septic (bacterial infection): hyperdynamic or hypodynamic
• neurogenic shock
• toxic shock

Psychogenic Shock

• type of vasogenic shock
• also known as fainting spells
• caused by sudden dilation of blood vessels which temporarily halts blood flow to the brain 

Neurogenic Shock

• type of vasogenic shock
• failure of the nervous system to control diameter of blood vessels
• causes pooling of blood and there is generally no actual blood loss
• classic signs of shock may not be present 

Septic Shock

vs

Systemic Inflammatory Response Syndrome

(SIRS)

• physiologic alternations and organ dysfunction seen with bacterial infections
• 2 or more changes in these 4 factors as follows: body temp, heart rate, respiratory function and peripheral leukocyte count
• Next is Sepsis: systemic host response to infection with SIRS plus a documented infection
• then Severe sepsis: sepsis plus end organ dysfunction or hypoperfusion
• last Septic Shock: sepsis with hypotension, despite fluid resuscitation with evidence of inadequate tissue perfusion

Septic Shock: Pathophysiology

• in septic shock due to bacterial infection, circ insuffic occurs when bacterial products interact with host cells and serum proteins to initiate a series of reacts that may ultimately lead to cell injury and death
• not only are these bacterial prod harmful themsevles, but widespread unregul host response to these also results in the elaboration or an extensive array of chemical mediators that lead to further cell damage
• septic shock develops in less than one half of patients with bacteremia. occurs in 40 % of patients with gram negative bacteremia and 20% of those patients with staphylococcus aureus bacteremia

Septic Shock: History

• fever (seperates septic from all other types of shock)
• chills
• sweating
• altered mental status: apprehension, anxiety, agitation

Septic Shock localizing symptoms

• head and neck infections-earache, sore thorat, sinus pain or congestion, nasal congestion or exudate, swollen lymph glands
• chest and pulmonary infections-cough(especially if productive), pleuritic chest pain, dyspnea
• abdominal and GI infections-abd pain, nausea, vomiting, diarrhea
• pelvic and genitourinary infections: pelvic or flank pain, vaginal or urethral discharge, dysuria, frequency, urgenic
• bone and soft tissue infections- focal pain or tenderness, focal erythema, edema

Causes of Cardiogenic Shock

• cardiomyopathy
• pulmonary embolism
• myocardial infarction
• heart disease
• arrhythmia
• aortic aneurysm
• cardiac tamponade
• cardiac contusion

Cardiogenic Shock

• cardiogenic shock is char by a decreased pumping ability of the heart causing a shock-like state with inadequate perfusion to the tissues
• it occurs most commonly in association with, and as a direct result of, acute ischemic damage to the myocardium

Septic Measurement Levels

• increased BP, heart rate, Cardiac output, cardiac contractility and body temperature
• Decrease in central veous pressure, pH, pCO2

Cardiogenic Measurement Levels

• decrease in BP, CO, Cardiac Contractility, pH, pCO2
• an increase in Left atrial pressure, and central venous pressure
• increase in heart rate initially and then a decrease

Hemorrhagic Measurement Levels

• Increase  in Heart rate and cardiac contractility 
• decrease in BP, CO, left atrial pressure, Central venous pressure pH, pCO2, and decrease in body temperature 

Treatment of Shock: Goal

• to restore normal tissue perfusion:
• blood pressure, pulse, respirations, skin appearance, sensorium, urine output(30-50cc per hour), hemoglobin 8-10 gm or hematocrit 24-30