OB Shelf - anatomy and physiology of pregnancy

• blood supply: external and internal pudendal arteries
• lymph: Medial group of superficial inguinal nodes
• nerve: 
•  - anterior → ilioinguinal nerves, genital branch of genitofemoral nerves; 
•  - posterior → perineal nerves and posterior cutaneous nerve of the thigh

• Blood supply:
• -Vaginal branch of uterin artery (primary)
• -Middle rectal and inferior vaginal branches of hypogastric artery (internal iliac)

• Nerve:
• -Hypogastric plexus (sympathetic)
• -Pelvic nerve (parasympathetic)

• Fundus: uppermost region of uterus
• Corpus: body
• Cornu: part that joins the fallopian tubes
• Cervix: inferior part of cervix that connects vagina via cervical canal
• Internal os: opening of the cervix on the uterine side
• External os: opening of the cervix on the vaginal side

• Mesometrium: visceral layer of peritoneum reflects against the uterus and forms this outmost layer
• Myometrium: smooth muscle layer of uterus
•      1. Outer longitudinal
•      2. Middle oblique
•      3. Inner longitudinal
• Endometrium: Mucosal layer, columnar epithelium

• Blood supply:
• -Uterine arteries (from internal iliacs)
• -Ovarian arteries

• Nerve supply:
• -Superior hypogastric plexus
• -Inferior hypogastric plexus
• -Common iliac nerves

• Connection: lateral pelvic wall to the uterus and adenexa
• Contains: fallopian tube, round ligament, uterine and ovarian blood vessels, lymph, utererovaginal nerves, ureters

• Connection: remains of gubernaculum; corpus of uterus down and laterally through the inguinal canal → labia majora
• Contains: nothing

• Connection: cervix and lateral vagina to the pelvic wall
• Function: supports the uterus

• Connection: extend from superior lateral uterus through superior fold of broad ligament to the ovaries
• Blood supply: uterine and ovarian arteries
• Nerve: Pelvic plexus (autonomic) and ovarian plexus)

• Lateral to medial:
• Infundibulum: the lateralmost part; free edge is connected to the fimbriae
• Ampula: widest section
• Isthmus: narrowest part
• Intramural part: pierces uterine wall

• Location: posterior aspect of broad ligament; attached to the broad ligament by the mesoovarium. NOT covered by peritoneum
• Blood supply: ovarian artery (from aorta at level L1); veins drain vena cava on the right, Left renal vein on the left
• Nerve supply: Aortic plexus
• Histology: covered by tunica albuginea (fibrous capsule); tunica albuginea is covered by germinal epithelium

• Last menstrual period (LMP)
• Ultrasound: progressively less accurate as GA increases. Should not be used past 20 weeks.

• Breast enlargement/tendernes (6 weeks GA)
• Areolar enlargement and increased pigmentation (after 6 weeks GA)
• Colostrum secretion (after 16 weeks GA)
• Nausea with or w/o vomiting (from missed period)
• Urinary frequency, nocturia, bladder irritability

Bluish discoloration of vagina and cervix, due to congestion of pelvic vasculature in pregnancy

• hCG (glycoprotein)
• Production: syncytiotrophoblast cell s in developing placenta shortly after implantation

Detection: 8-10 days after fertilization

• Also elevated in:
• -hydatidiform mole
• -choriocarcinoma
• -germ cell tumors
• -Ectopically producing breast cancers and large cell carcinoma of the lung

• Levels should double every 48 hours in early pregnancy
• 1 wk: 5-50mU/mL - assays detecting 25mU/mL recognize pregnancy with 95% sensitivity by 1 week post LMP
• 2 wks: 50-500mU/mL
• 3 wks: 100-10,000mU/mL
• 4 wks: 1,000-30,000mU/mL
• 5 wks: 3,500-115,000mU/mL
• 6-8 wks: 12,000-270,000mU/mL
• 8-12 wks: 15,000-220,000mU/mL
• 20-40 wks: 3,000-15,000mU/mL

• False positives:
• -proteinuria
• -Urinary tract infection

• False negatives:
• -too early
• -urine is dilute

• confirm urine hCG
• Diagnosing ectopic pregnancy
• Monitoring trophoblastic tumors
• Screening for fetal abnormalities

• 12 wks: barely palpable
• 15 wks: midpoint between pubic symphysis and umbilicus
• 20 wks: at the umbilicus
• 28 wks: 6 cm above the umbilicus
• 32 wks: 6 cm below the xyphoid process
• 36 wks: 2 cm below xyphoid process
• 40 wks: 4 cm below xyphoid process

• Earliest: 8 weeks GA
• Worrisome: not auscultated by 11 weeks' GA, should do an ultrasound

***

• Increased by ~8.5 L
• Composed of: fetal water, amniotic fluid, placental tissue, maternal tissue, edema, increased hydration of connective tissue, generalized swelling

• Increased gradually from 10 weeks to 36 weeks by 50 to 100 kcal/day
• Final 4 weeks, requirement increased by 300 kcal/day

• Ideal: 25 to 35 lbs during pregnancy
• T1: 1.5 to 3 lbs
• T2 and T3: 0.8 lbs/wk
• Obese: should gain less that 25 lbs

• Overal increases in the second half of pregnancy
• Carbohydrates: placenta is freely permeable to glucose
• Insulin: increased in first half; insulin resistance in second half
• Amino acids: plasma concentration of aa fall during pregnancy (hemodilution)
• Lipids: all raised (most increase in triglycerides); cross the placenta
• Fat: deposits in early pregnancy; primary source of energy in mid pregnancy
• Cholesterol: increase turnover, all increased during pregnancy; raised in postpartum
• Drugs: phenytoin falls during pregnancy; caffeine half-life is doubled; antibiotics are cleared more rapidly

• Screen at 26 to 28 weeks' GA
• increased insulin in first half; insulin resistance in second half (physiologic)

• Syncope:
• -venous pooling in lower extremities
• -dehydration
• -hypoglycemia
• -postprandial shunting of blood flow to the stomach
• -overexertion during exercise

• Psychiatric sx:
• -Hormonal changes of pregnancy
• -Progesterone → tiredness, dyspnea, depression
• -Euphoria secondary to endogenous corticosteroids

Fetal P_CO2 > maternal PCO2... must reset maternal respiratory center. Mechanism:

• 1. Progesterone reduces the CO2 threshold at which respiratory center is stimulated and increases respiratory center sensitivity
• →hyperventilation of pregnancy

2. Tidal volume (TV) increases by 200ml

3. Vital capacity (VC) increases by 100 to 200ml

• CO increases by 40% by week 10
• -10% increase in stroke volume
• -10 to 15% increase in pulse rate
• -enlargement of heart and left ventricles
• -heart is displaced anterolaterally secondary to rise in diaphragm (ECG changes can mimic ischemia)

• Venous system: venous dilation
• -relaxation of vascular smooth muscle
• -pressure of enlarging uterus on IVC and iliac veins

• After midpregnancy: 90% have S₃
• Systolic ejection murmurs: 96% of pregnant patients
• Diastolic murmurs: never normal
• During labor: CO increases by 30% during each contraction (increase in stroke volume, not heart rate)

• Reflux esophagitis
• -increased intragastric pressure
• -progesterone causes a relative relaxation of esophageal sphincter

Constipation: secondary to progesterone, which relaxes intestinal smooth muscle and slows peristalsis

• Gallbladder:
• -increased size
• -empties slower
• -Cholestasis, hormonal effects (?); also seen in some users of OCPs and hormone replacement therapy

• Liver:
• -hepatic function increases
• -Plasma globulin and fibrinogen concentrations increase
• -synthetic rate of albumin increases
• -Velocity of blood flow in hepatic veins decreases
• -Serum alkaline phosphatase increases largely due to placental production

• Urinary stasis: decreased peristalsis, mechanical compression
• Asymptomatic bacteruria: 5 to 8% of pregnant women
• Urinary frequency increases: bladder compression by uterus, fetal head descent
• Nocturia: physiologic after T1 (up to 4 times per night)
• Stress incontinence: relaxation of bladder supports

• Bladder tone decreases
• bladder capacity increases

• Progressive dilatation and kinking in > 90% of women at >6 weeks
• -Decreased urine flow rate
• -dilatation is secondary to physical obstruction
• -extends up to calyces → enlarged kidneys

• RPF increases from T1: 30 to 50% above non-pregnant levels by 20 weeks; remains elevated until 30 weeks, then slowly declines
• GFR: increases; 60% above nonpregnant levels by 16 weeks, remains elevated

• Tubules lose some of their resorptive capacity: amino acids, uric acids, glucose are not as completely reabsorbed
• Iincrease protein loss of up to 300mg/24hr

• Plasma volume: increased by 50% (hemodilution)
• RBC: increases progressively during pregnancy (Ret count increases by >2%); MCV ususally increases
• Hemoglobin: HbF concentration increases 1 to 2% during pregnancy
• Erythrocyte Sedimentation Rate: rises in early pregnancy due to increase in fibrinogen
• WBC: neutrophils increases in T1, rise until 30 weeks (number and activity/function); lymphocyte counts remains unchanged (function is suppressed)
• Platelets: reactivity increased in T2 and T3, returns to normal post partum

• hCG (luteotropic): Co-regulates and stimulates adrenal and placental steroidogenesis; stimulates fetal tissue to secrete testosterone. Possesses thyrotrophic activity
• hPL (human placental lactogen): anti-insulin and growth hormone-like effects (impaired maternal glucose and FFA release)

• Increases in weight and sensitivity
• Prolactin: increases within a few days postconception; 10- to 20-fold higher at term
• FSH: blunted response to GnRH; progressive decreased response
• LH: response to GnRH diminishes and finally disappears

• Plasma cortisol/other corticosteroids increase progressively from 12 weeks to term; 3-5 times the normal levels
• Half-life of plasma cortisol increases, clearance is reduced

• Thought to be due to excess estrogen in pregnancy:
• -Increases in size
• -T3/T4 and Thyroxine-binding globulin increase (mother should remain euthyroid)

• PTH increases → increases maternal calcium absortpion (offset maternal loss to fetus)
• At term, PTH levels are higher in the mother, but calcitonin is higher in the fetus

• Plasma protein concentrations fall by 20 weeks, mostly due to a fall in serum albumin
• Reduced colloid osmotic pressure in plasma → edema in pregnancy

• Size of islets of Langerhans increases
• Number of beta cells increases
• Number of insulin receptor sites increases
• Insulin: rises in pregnancy, but insulin resistance increases as well
• Glucagon: levels are slightly raised in pregnancy, not as much as insulin levels

• Pruritic urticarial papules and plaques of pregnancy (PUPPP) **
• Papular eruptions (prurigo gestationis and papular dermatitis)
• Pruritis gravidarum**
• Impetigo herpetiformis
• Herpes gestationis

• pruritic urticarial papules and plaques of pregnancy
• Onset: T2-T3
• Severely pruritic
• LEsions: erythematous urticarial papules and plaques
• Distribution: abdomen, thighs, buttocks, occasionally arms and legs
• Incidence: common (.25-1%)
• No increased fetal morbidity/mortality
• Intervention: topical steroids, antipruritic drugs

• Increased in pregnancy causes:
• Linea nigra: black line of the abdomen that runs from above the umbilicus to the pubis
• Darkening of nipple and areola
• Facial cholasma/melasma: brown hyperpigmentation in exposed areas such as face
• Suntan acquired in pregnancy lasts longer than usual

• Spider nevi are common (branched growth of dilated capillaries on the skin)
• Palmar erythema

Striae on the abdomen, breasts, etc.

Grow more rapidly during pregnancy

• Shed rate is reduced
• Excess retained hair is often lost in the puerperium, secondary to maternal emotional stress

• Vaginal epithelum hypertrophies
• Increased quantity of glycogen-containing cells shed into vagina
• Connective tissue decreases in collagen content; increase in water content
• Vaginal becomes more acidic (pH = 4 to 5); hinders growth of most pathogens, favors growth of yeast

• Hypertrophy and hyperplasia of myometrial smooth muscle, secondary to:
• -steroid hormones
• -Uterine distension and wall thinning
• Term uterus weighs 1,100g with 20-fold increase in mass

• Increased length, muscular content, diameter
• In pregnancy, may contract spontaneously, or in response to uterine movement
• In labor: contractions of ligaments pulls the uterus forward

• Nonpregnant: uterine artery
• Pregnant: ovarian arteries contribute 20 to 30% of blood supply
• Uterine arteries dilate to 1.5 times their diameter

• Softening: accumulation of glycosaminoglycans and increased water content and vasculatiry
• "cervical ripening": takes place over last few weeks of gestation
• Antibacterial mucous plug of the cervix: within endocervical canal

• uterine isthmus: small region of uterus that lies between the uterine corpus and the cervix
• At 12 weeks: isthmus enlarges and thins
• Labor: isthmus expands and is termed the lower uterine segment

• ovum leaves the ovary, carried into the fallopian tube
• surrounded by its zona pellucida
• Oocyte has completed its first meiotic division and carries its first polar body

• Occurs within 24hrs after ovulation in the ampulla (third of the tube adjacent the ovary
• Fertilization: signals the ovum to complete meiosis II and to discharge an additional polar body

• Ovum remains in the ampulla for 80 hours, travels through isthmus of fallopian tube for 10 hours
• Egg → multicellular blastomere
• Blastomere passes into the uterine cavity
• blastomere → blastocyst, floats in endometrial cavity for 90 to 150 hours

• Day 5 to 6 of development: blastocyst adhere to the endometrium
• After attachment, endometrium proliferates around the blastocyst

• During week 2, cells in outer cell mass differentiate into trophoblasts
• Trophoblastic shell forms initial boundary between embryo and the endometrium
• Trophoblasts near the myometrium form placental disk; others form chorionic membranes

• Endometrium or lining of uterus during pregnancy is termed decidua
• Maternal RBCs may be seen in the trophoblastic lacunae in the second week postconception

• Embryo development
• wk 1: Early morula; no organ differentiation
• wk 3: Double heart recognized
• wk 4: initial organogenesis
• wk 6: Genetic sex determined
• wk 8: Sensory organ development and nondifferentiated gonadal development
• Fetal development
• wk 12: Brain configuration roughly complete, sex now specific, blood forming in marrow, external genitalia forming, uterus no longer bicornuate
• wk 16: Fetus is active, sex determined by visual inspection, myelination of nerves, heart muscle well developed, vagina and anus open, ischium ossified
• wk 20: Sternum ossifies
• wk 24: Primitive respiratory movements
• wk 28: Nails appear and testes at or below internal inguinal ring
• wk 36: Earlobe soft with little cartilage, scrotum small with few rugae
• wk 40: Earlobes stiffen by thick cartilage, scrotum well developed

• 4: blastula
• 7-12: implantation
• 13: Primitive streak
• 16: Neural plate
• 19-21: First somite
• 23-25: Closure of anterior neuropore
• 25-27: Arms bud, closure of posterior neuropore
• 28: Legs bud
• 44: sexual differentiation

• adapts over T2 and T3; primary producer of steroid hormones after 7 weeks' GA
• Blood supply: arcuate and radial arteries during normal pregnancy is high with low resistance (resistance falls after 20 weeks)

• Division of embryos before differentiation of trophoblasts (< day 2 or 3): 2 chorions, 2 amnions
• Division of embryos after trophoblast differentiation and before amnion formation (days 3 to 8): 1 placenta, 1 chorion, 2 amnions)
• Division of embryos after amnion formation (day 8 to 13): 1 placenta, 1 chorion, 1 amnion

• Source: placenta
• Function: Maintains the corpus luteum; stimulates adrenal and placental steroidogenesis

• Source: Trophoblasts
• Function: Stimulates an increase in circulating maternal free cortisol

• Source: trophoblasts
• Function: Antagonizes insulin; maternal glucose intolerance, lipolysis, proteolysis

• Source: placental tissue and decidua
• Function: Stimulates placental ACTH release and participates in the surge of fetal glucocorticoids associated with late T3 fetal maturation

• Source: Decidualized endometrium
• Function: Regulates fluid and electrolyte flux through the fetal membranes

• Source: Yould sac, fetal GI tract, fetal liver
• Function: regulates fetal intravascular volume (osmoregulator)
• -MSAFT peaks between 10 and 13 weeks' GA, then declines
• -Detectable as early as 7 weeks' GA
• MSAFP is decreased in  pregnancies with Down's syndrome
• Amniotic fluid AFP and maternal serum (MSAFP) are elevated in association with neural tube defects and low in trisomy 21

• Function: estrogens affect uterine vasculature
• Estradiol: maternal ovaries (wks 1 through 6); placenta after T1. during T3, low estradiol levels are associated with poor outcomes
• Estrone: maternal ovaries, adrenals, and peripheral conversion for first 4 to 6 weeks; placenta therafter
• Estriol: placenta (need living fetus)

• Source: corpus luteum before 6 weeks, placenta therafter (from LDL)
• Function: affects tubal motility, endometrium, uterine vasculatur, parturition; inhibits T lymphocyte-mediated tissue rejection
• *abortion will occur in 80% of women with progetserone levels under 10ng/mL

• Source: Decidual tissue
• Function: Suppresses the maternal immune rejection response of the implanted coceptus

• Source: fetal adrenal gland
• Function: regulatory precursor of corpus luteum progesterone production; lipoprotein utilized in fetal adrenal steroidogenesis