What is the two cell stage of fetilization?
First three days of development in the fallopian tube
What is the morula and when does it arrive in the uterine cavity?
1. Solid Mass of Blastomere Cells-MORULA
2. Day 4- Arrives in the uterine cavity
1. What happens in Day 5?
2. What is the outter layer of this called?
3. Inner layer?
1. Blastocyst stage
2. Outer layer = Trophoblast= Placenta&Fetal Membranes
3. Inner layer = Cell Mass to become Embryo and Fluid
What day is "Hatching"?
Wat structures are involved? 5
What happens on day 6-7?
Implantation-Trophoblast Invades Endometrium
1. In response to 17-OH progesterone from the corpus luteum, the endometrium glands are filled with what? 3
2. Implantation of the ________ takes several days.
3. The conceptus is genetically different from the mother. How many of the chromosomes are from mother?
4. Genetically foreign cells usually rejected by the immune system. This does not occur during normal pregnancy— why?
-mucus and a
-rich blood supply. (The secretory endometrium.)
3. Only half
4. due to modifications of the mother’s immune system
What are the stem cells of the placenta?
PROGENITOR CYTOTROPHOBLAST CELL
1. Placenta: Which cells are “Invasive” into decidua and myometrium (not too dissimilar to metastasizing cancer cells)?
2. “Invasive” into the ___________ which are remodeled into wide uteroplacental arteries (which anastomose with ______________ to form a lacunar system of low resistance).
3. Form core of villi (covered by what?)
1. Extravillous Cytotrophoblast (inner)
2. spiral arteries, endometrial veins
Differentiation of Progenitor Villous Trophoblast Cells
1. These are able to become what?
2. Forms the placental villi with base of what with overlying syncytiotrophoblast on surface?
3. What does the Progenitor Villous Trophoblast Cells form?
4. What is its function? 3
5. Also, forms ____ umbilical arteries and ____ vein
2. cytotrophoblast cells (Langhans layer)
3. Specialized epithelium without distinct cell boundaries covering villous tree:
-transport of gases,
-nutrient and wastes as well as
-synthesis of peptide and steroid hormones that influence placental, fetal and maternal systems
5. two, one
Influenced by 1.____________ and later with invasion of trophoblasts (implantation), the 2.________ cells of the secretory endometrium become 3.__________ CELLS
Decidual cells directly under implantation site form what? 2
1. the basal plate of the PLACENTA (decidua basalis) and
2. a factor limiting myometrial invasion (placenta accreta, increta and percreta)
What always separate the embryonic circulation from maternal blood and decidua?
A layer of trophoblast cells
1. What is Nitabuch's layer?
2. Possible role in preventing what?
3. Allows separation of what?
1. A layer of fibrin between the boundary zone of compact endometrium and the cytotrophoblastic shell in the placenta
2. host/graft rejection
3. placenta after delivery
Functions of the Placenta? 6
1. The interface between mother and fetus
2. Prevents rejection of fetal allograft
3. Enables respiratory gas exchange
4. Transports nutrients
5. Eliminates fetal waste products
6. Secretes peptide and steroid hormones
Metabolic Functions of the Placenta
1. Glycogen synthesis –uptake of glucose from maternal circulation; glycogen as an energy reserve
2. Cholesterol synthesis – as a precursor for production of progesterone and estrogen
3. Removal of Lactate-a waste product of placental metabolism is transferred to maternal circulation
4. Protein metabolism
Placental Peptide Hormones
1. Human chorionic gonadotropin(hCG)
2 . Human placental lactogen (hPL)
3. Placental corticotropin-releasing hormone (CRH)
4. Insulin-like growth factors (IGF)-regulate fetal growth
5. Vascular endothelial growth factor (VEGF)
6. Placental growth factor
Describe the following functions of each of the hormones?
1. Human chorionic gonadotropin(hCG)?
2 . Human placental lactogen (hPL)?
3. Placental corticotropin-releasing hormone (CRH)? 2
1. Human chorionic gonadotropin(hCG)-maintains corpus luteum production of progesterone until placenta takes over at 6-8 weeks; regulates placental steroid production
2. Human placental lactogen (hPL)-antagonizes maternal secretion of insulin to increase fetal glucose supply
3. Placental corticotropin-releasing hormone (CRH) -
-stimulates fetal ACTH resulting in fetal adrenal making DHEA-S as precursor to placental estrogen
-in latter gestation, fetal cortisol stimulates CRH release which stimulates fetal ACTH that acts as an endocrine mediator of onset of labor
What are the placental Steriod hormones?
3. Enzymes to degreade maternal glucocorticoids
Describe the following functions of these hormones:
3. Enzymes to degreade maternal glucocorticoids?
1. Progesterone – maintains a non-contractile uterus; also anti-inflammatory and immunosuppressive to protect fetus
2. Estrogens – stimulated by placental HCG; also maternal & fetal blood supply DHEAS (dehydroepiandrosterone sulfate) as substrate for additional estrogens (mostly from fetal adrenal)
3. Enzymes to DEGRADE maternal Glucocorticoids – placenta regulates exposure of fetus to glucocorticoids. This has an important role in regulating fetal organ development and maturation
1. PLacental transfer/transport occurs where?
2. What are the kinds of transport across the placenta? 6
1. Occurs at the SYNCYTIOTROPHOBLAST LAYER
-CO2 and O2 exchange
-Amino acid: fetus dependent on these for protein synthesis
-Fatty acids from breakdown of maternal triglycerides
-Immunoglobulin G (Maternal antibodies)
-Drugs (high MW least likely)
1. Enlargement of the uterus
2. Breast enlargement and growth of ductal structure
3. Enlargement of the external genitalia
4. Relaxation of pelvic ligaments
5. Affects many aspects of fetal development
Maternal Physiology-Progesterone functions
1. Induces endometrial secretory cells to decidual cells
2. Contributes to development of the conceptus before implantation, affects cell cleavage in the developing embryo
3. Inhibits myometrial contractions
4. May be involved with immune tolerance of fetus
5. Influences breasts for lactation
6. Helps develop thick mucus plug of the cervix
7. Along with estrogen changes cervix, vagina, and vulva to allow for sufficient stretching to allow delivery
What hormone rises in early pregnancy?
What hormones rise in late pregnancy? 2
Opathalamic changes in pregnancy? 5
1. Cornea thickens – may cause problems for contact lens wearers; may cause blurred vision. Pregnancy is contraindication for refractive surgery****
2. Decrease in intraocular pressure
3. Visual field changes or double vision are abnormal
4. Diabetic retinopathy may worsen dramatically during pregnancy
5. With toxemia of pregnancy, choroidal vascular insufficiency causes secondary retinal detachments
Dental Changes in Pregnancy?
1. Gingivitis of pregnancy
2. Epulis of pregnancy
Describe what the following are:
1. Gingivitis of pregnancy?
2. Epulis of pregnancy?
1. Gingivitis of pregnancy - Hormonal changes soften the tissues in mouth contributing to bleeding or inflammation.
2. Epulis of pregnancy- a hyperplastic, granulomatous lesion. Composed mainly of capillary vessels and endothelial proliferation. Referred to as "pregnancy tumor”. (Similar lesions are also seen in non-pregnant individuals with dilantin therapy.)
Gastrointestinal Changes in Pregnancy
1. Relaxation of esophageal sphincter – increased incidence of GERD
2. Decreased peptic ulcer disease-due to increased mucus and decreased gastric secretion
3. Gallbladder empties incompletely in response to meals during pregnancy
4. Delayed gastric emptying , slowed small bowel transit and decreased large bowel peristalsis – constipation, fecal impaction (related to high progesterone)
5. Increased portal venous pressure (but not central venous pressure)
6. Nausea & vomiting (morning sickness)(nausea gravidarum) – 4 to 16 weeks
7. Hyperemesis gravidarum - persistent and severe N&V = weight loss, dehydration and electrolyte imbalances;caused by rapidly rising serum levels of hCG and estrogen
1. Hyperemesis Gravidarum is more common in what pts? 2
2. What Rx may be required in this?
3. How can you treat Nausea & vomiting (morning sickness)(nausea gravidarum) – 4 to 16 weeks?
1. More common in a multiple pregnancy or hydatidiform mole
2. IV fluids, antiemetics and rarely TPN may be required.
3. Vitamin B6 (Pyridoxine) 50-100 mg daily
Renal and Urinary Changes in Pregnancy
1. Progesterone relaxes bladder wall and reduces ureteral tone and peristalsis; effect may persist 12-16 wk postpartum
2. Physiological hydroureter of pregnancy – can hold 200-300 ml of urine; enlarging uterus can compress ureter at pelvic brim (R>L)
3. Hydronephrosis is common (R>L)
4. Changes predispose pregnant women to UTIs and pyelonephritis
Urinary Bladder in Pregnancy
1. Enlarging uterus displaces and flattens bladder decreasing capacity; associated with what?
2. Common complaints are what? 2
-increased frequency and
-nocturia. Be vigilant about evaluating for UTI
Urinary Bladder in Pregnancy
1. What complication is associated with 2-7% of pregnant women?
2. What is it associated with? 3
3. ANY pregnant woman with what MUST be admitted to the hospital?
1. ASYMPTOMATIC BACTERURIA
2. associated with
-preterm labor and
Treatment prevents 80% of cases of pyelonephritis and reduces the risk of preterm delivery
Renal Function in Pregnancy
1. Both kidneys increase in size by how much?
2. Renal blood flow and glomerular filtration _________ 40-50% by mid trimester
3. Creatinine drops ____mg/dl; BUN ___% drop and uric acid ___% drop
4. _______________ of pregnancy causes respiratory alkalosis which is compensated by renal excretion of bicarbonate.
5. Extracellular volume _______?
1. 1-1.5 cm
3. 0.3, 50, 33
4. Hyperventilation (low PaCO2)
5. increases, (total body water increases 6-8 L; two-thirds of this in extravascular space)
Cardiovascular Changes in Pregnancy
7 (two important ones)
Stroke volume – increases 10-30%
1. Heart rate – increases 12-18 beats/min
2. Cardiac output increases 40% by 20-24 wk
3. Systolic vascular resistance – decreases 5% - 10 mmHg
4. Systolic BP – decreases 4-6 mmHg***
5. Diastolic BP – decreases 8-15 mmHg ****
6. Mean BP – decreases 6-10 mmHg
7. Oxygen consumption for any given level of exercise– increases 20%
Peripheral Cardiovascular Changes in Pregnancy
1. Uterine blood flow – appx ____ ml/min
2. Maternal blood flow to placental site – ____ ml/min
3. Muscle mass of heart ______?
4. Heart is shifted to the____?
5. Apical pulse moves where?
6. ________ heart sounds?
7. Wide split S1 and S2 heart sounds by ___ trimester
5. to the 4th intercostal space at midclavicular line
1. What is supine hypotensive syndrome?
2. Causing what? 2
1. VENOUS COMPRESSION of inferior vena cava
Physiologic Anemia of Pregnancy
1. Plasma volume changes how?
2. Red cell mass changes how? why?
3. Total blood volume does what?
4. Anemia is common in normal pregnant women and perhaps is beneficial. Why?
5. Anemia defined as what? 2
1. increases 50%
2. increases 20-35% - hemodilution and a decrease in hemoglobin concentration
3. increases 40-50%
4. decrease in viscosity may help with perfusion
5. Hg less than 11 (or less than 10.5 in 2nd tri) or Hct less than 33
Iron Requirement in Pregnancy
1. Average iron stores in normal men - ___ mg
2. Average iron stores in normal women - ____ mg
3. Total iron requirements during pregnancy – _____ mg
4. _____ mg of iron absorbed/day from food – 270-540 mg
Iron deficit – 256-480 mg
5. The amount of iron absorbed from diet plus stored iron is insuffient for what?
5. to meet the requirements for pregnancy
Should take what? 3
1. Women of reproductive age should take folic acid 4-8 mg (400-800 mcg) daily
2. Begin oral iron 6 months before conception to offset iron lost with menses
3. If vitamin preparation contains magnesium (all prenatal vitamins contain magnesium) take the vitamin preparation and the iron tablets at different times of the day – magnesium interferes with iron absorption
--Iron tablets must be kept out of reach of small children – iron tablets can be lethal in small children
When is neural tube closure complete?
NEURAL TUBE CLOSURE COMPLETE BY 28 DAYS POST-CONCEPTION = 6 wks from LMP
Coagulation Changes in Pregnancy
1. Increase of what? 2
2. Decrease in protein__levels and inhibition of________?
3. What does this result in?
4. These physiological changes may be important for minimizing what?
5. there is a prothrombotic state with an increased risk of what during pregnancy and the post-partum period (6-8 weeks to baseline)?
-procoagulant fibrinogen and
-clotting factors II, VII, VIII, X, IX, XII and XIII
2. S, fibrinolysis
3. =Hypercoagulable state
4. intrapartum blood loss
Respiratory Tract Changes
1. Increased nasopharyngeal blood flow
2. Upper respiratory tract: increased phagocytic activity
3. Residual lung capacity decreases 20% due to enlarging uterus
What increased nasophyarngeal blood flow cause?
1. nose bleeds (epistaxis)
2. nasal congestion
3. polyp (specific to pregnancy)
Respiratory Tract Changes: Progesterone Effects
1. Stimulates respiratory drive centrally
2. Minute ventilation increases 50%without a change of respiratory rate
3. Tidal volume increase
4. Oxygen consumption increases 20% to meet the demands of the placenta, fetus, and maternal organs
5. PaO2 ranges from 100-110 mmHg
6. PaCO2 decreases to 27-32 mmHg
Musculoskeletal Changes in Pregnancy
1. 25-35 lb weight gain on average during pregnancy
2. Joint laxity in anterior and posterior ligaments of the lumbar spine
3. Separation and stretching of abdominal muscles put more strain on paraspinal muscles
4. SI joints and pubic symphysis widen and have increased mobility
5. Pelvis tilted more anteriorly, increasing use of hip extensors, abductor muscles and stance is widened
1. MSK changes in pregnancy: Joint laxity in anterior and posterior ligaments of the lumbar spine manifests how?
2. Widening of Pubic symphysis by 10-12 weeks due to _________ (made by CL, decidua, placenta)
1. Exaggerated lumbar lordosis and forward flexion of the neck
Musculoskeletal Changes in Pregnancy
1. Carpal tunnel syndrome in pregnancy happens why? 3
2. Sciatic nerve pain in pregnancy happens how?
3. When does this go away?
4. What may they need?
1. Pregnancy causes
-fluid retention and
-swelling in general
2. – common - extra weight and pressure caused by pregnancy can cause compression of the sciatic nerve.
3. The symptoms will usually go away after childbirth.
4. May require use of a cane, walker, or even crutches
Endocrine Adaptations in Pregnancy
1. Interactions of the fetal-placental-maternal unit
6. Adrenal glands
Hypothalamic Hormones in Pregnancy
How are the following affected:
1. Gonadotropin- releasing hormone (GnRH)?
2. Corticotropin-releasing hormone (CRH)?
1. Gonadotropin-releasing hormone (GnRH) – levels increase during pregnancy, main source is placental GnRH
2. Corticotropin-releasing hormone (CRH) – placental HPA axis is stimulated by maternal cortisol to release CRH from the decidua-trophoblast-membranes
1. placental CRH drives what?
2. High CRH levels in who?
1. Placental CRH drives the maternal and fetal pituitary
2. High CRH levels in maternal circulation
Anterior Pituitary Gland in Pregnancy
1. Decline in circulating gonatotropins due to what?
2. What declines, replaced by placental-derived GH?
3. ________ in ACTH – What kind of state does this make?
4. _____________ mildly reduce in 1st trimester and modestly elevated at term
5. Serum prolactin levels ______________ throughout pregnancy
1. high estradiol and progesterone levels
2. Growth hormone (GH)
3. Increase, pregnancy state hypercortisolism
4. Thyrotropin (TSH)
Intermediate Lobe of the Pituitary in Pregnancy
1, Increases in volume
2. Melanocyte-stimulating hormone (MSH) elevated
-Melasma /cholasma ( mask of pregnancy)
3. Fetus is a source of alpha-melanotropin (skin changes) – stimulates fetal growth
Posterior Pituitary in Pregnancy
1. Antidiuretic hormone (ADH) - pregnant women are less sensitive to the action of ADH because of what?
2. ADH has major role in controlling what?
3. Therefore, slight decrease in plasma sodium of ____ mEq/L?
1. an inactivating enzyme from placenta for ADH
2. osmolality of plasma (largely sodium concentration).
Posterior Pituitary in Pregnancy
1. Maternal plasma levels ________ throughout pregnancy?
2. Involved in onset of what?
3. Involved in what with nipple stimulation triggering release of oxytocin?
3. milk “let down” during lactation
Parathyroid Glands in Pregnancy
1. PTH levels change how?
2. Maternal Ca+ homeostasis adapts to meet the calcium needs of the fetus. What are these needs?
3. PTH facilitates transfer of _______ across placenta to fetus?
4. PTH mobilizes calcium from what?
5. Maternal calcium intake requirement changes how?
1. PTH levels increase
2. – 200 mg/day in the third trimester and 30 grams total
4. maternal skeleton
Thyroid Glands in Pregnancy
1. Increased what due to estrogen?
2. Which thyroid hormones are increased and which stay normal?2 and 2
1. Increased thyroxine-binding globulin (TBG) due to estrogen
-free T4 and
Thyroid glands in pregnancy
1. Increased TSH stimulated by _____ (they share the same alpha unit)?
2. Increased maternal ______ needs (Investigate any goiter)
Adrenal Glands in Pregnancy
1. Cortisol is also affected by placental____?
2. Renin-angiotensin-aldosterone system is stimulated in pregnancy by what?
3. Regulates aldosterone secretion which stimulates what? 2
4. Aldosterone levels ___ throughout pregnancy?
5. Why does the uterine artery demonstrates refractoriness to vasoconstriction by infused angiotensin II?
2. high levels of estrogen and progesterone
3. absorption of Na+ and excretion of K+
5. Decreased vascular responsiveness to angiotensin II
Glucose Metabolism in Pregnancy
1. Insulin-resistant state develops in the mother sparing glucose for the what?
2. Diabetogenic hormones? 4
3. Maternal what have detrimental effects on the developing embryo at several stages of development - birth defects?
4. Hyperplasia of what?
5. Increased _____ secretion
1. pregnant uterus
-chorionic somatomammotropin (human placental lactogen) and
3. hyperglycemia and diabetes
4. pancreatic beta cells
Glucose Metabolism in Pregnancy
1. Fasting glucose - levels _________ by a median of 3 mg/dL in the first trimester
2. Relative insulin resistance and hypoglycemia with increased what?
3. Mother preferentially uses fat for fuel preserving what for the fetus? 2
4. Minimizes _______ catabolism
5. Placenta readily tansfers glucose, amino acids, and ketone bodies but is impermeable to what?
3. glucose and amino acids
5. large lipids
Lipid Metabolism in Pregnancy
1. Which lipid levels rise during pregnancy? 2
2. High TG concentrations provide what?
3. Elevated LDL cholesterol aids placental what?
4. 2nd trimester: What kind of accumulation?
5. 3rd trimester maternal __________ of stored fat
6. What is Leptin?
-Serum triglycerides (300%) and
2. maternal fuel
4. fat accumulation
6. - a hormone secreted by adipose tissue and the placenta plays a key role in fat metabolism
Average daily allowance for protein in pregnant women?
Other Metabolic Changes
1. Water – average increase is _______ –
2. evident as ______________ – a normal finding in many pregnant women
1. 3 liters
2. ankle and leg edema
Changes of Reproductive Organs in Pregnancy
1. Uterine enlargement from _________ gm
2. At term, ____% of cardiac output is to the uterus
3. Cervix, vagina and vulva – __________ blood supply causing cyanotic changes.
4. Also, cervix softens (due to relaxin) allowing what?
5. Vulvar varicosities – disappear when?
6. Vulvar condylomata – grow how during pregnancy? Diappear when?
1. 70 gm to 1000gm
4. dilation and passage of baby.
5. after delivery
6. rapidly during pregnancy. Usually disappear after delivery (probably a result of immunological changes).
Hair, nail, Skin changes in pregnancy? 6
2. Rosacea worsens and clears after delivery
3. Increase or decreased growth rate
4. Many have some degree of hirsutism on face, limbs and back
5. Delivery may initiate a shedding cycle
6. Nails grow faster, but may be more brittle, may have transverse grooves and onycholysis
Vascular Changes in Pregnancy
1. Spider telangiectasias
2. Palmar erythema
3. Saphenous, vulvar, hemorrhoidal varicosities in 40% of women
1. What is the most common pregnancy related dermatosis (1 in 130-300 Pregnancies)?
2. Associated with what symptoms? 2
3. Develops in what trimester?
4. First appears when?
5. Common in what kind of pregnancies? 2
6. Treatment? 2
1. Pruritic Urticarial Papules and Plaques of Pregnancy
2. PUPP-associated rash with intense pruritis
3. Develops in the 3rd trimester
4. First appears on the abdomen
5. Common in first pregnancies and multiple gestations
6. Treatment – antihistamines and topical corticosteroids
Immunologic Changes in Pregnancy
Promote maintenance of the antigenic fetus in the maternal environment
1. Suppression of what?
2. Levels of most cytokines are ___________ particularly during the initial 20 weeks of pregnancy, which is an important phase to sustain the fetus.
Whether this suppressed immune system translates into an increased risk of infections during pregnancy is still not clear with the available data
1. T-cell-mediated immunity
Breast Changes in Pregnancy
1. Stimulated by what? 2
2. What kind of increase in size?
3. How do nipples and areola change?
4. _____________ in late pregnancy and after delivery
1. Stimulated by both estrogen and progesterone
2. 25-50% increase in size
3. Nipples and areola increase in size and pigmentation
4. Colostrum secretion
Breast Changes in Early Pregnancy
1. Influenced by what?
2. Symptoms? 4
1. Influenced by chorionic gonadotropin
-Increase in size
-Breasts may tingle with temperature change
-Secretory glands begin to develop
Breast Changes in Late Pregnancy
1. Proliferation of new acini is reduced
2. Lumen of units already formed become distended with secretory material (colostrum)
3. Parturition – new wave of mitotic activity and further growth and differentiation with milk secretion
Describe Stage I and II of lactogensis?
1. Secretory initiation – Stage I
2nd half of pregnancy – during late pregnancy many women are able to express colostrum
2. Secretory activation – Stage II
copious milk production after delivery – triggered by rapid decline in progesterone and elevated levels of prolactin, cortisol, and insulin