Wagner-Physiology Of Pregnancy

Front 1

describe the transformation of the trophoblast in the development of the placenta

Back 1

chorion-formed when the cytotrophoblastic layer is 2 cells thick; the blastocystic pole is covered by the chorion frondosum which is covered by the decidua capsularis
Further embryonic development makes the frondosum poorly vascularized, appears smooth(chorion laeve); decidua capsularis and parietalis merge to form the decidua vera, which lays contiguous with the chorion laeve as the fetal membrane
placental (chorionic) villi-cytotrophoblast proliferation is greater here, and this part of the chorion is >2 cells thick
Cytotrophoblastic cells project into the syncytium, forming a network of chorionic villi; these cells serve to anchor the fetal portion of the placenta to the decidua or to tap into the maternal blood supply

Front 2

describe the role of the chorionic villi in anchoring the fetal placenta to the decidua

Back 2

cytotrophoblasts express an array of cell adhesion molecules that enable them to anchor to the decidual extracellular matrix:
1. E-cadherin-involved w/ the trophoblast adherence and attachment during blastocyst implantation
2. Integrin-helps mediate cytotrophoblast adhesion to the decidual extracellular matrix
3. Oncofetal fibronectin (trophouteronectin and trophoblast glue)-glycoprotein expressed by the cytotrophoblasts that plays a role in the cytotrophoblast migration and attachment to the maternal decidua

Front 3

describe the role of the synctium in establishing uteroplacental circulation

Back 3

Fetal development depends on the efficient exchange of maternal and fetal blood across the placenta by tapping into the maternal blood supply, and by developing fetal capillaries within the chorionic villi
role of the syncytium-syncytium has the capacity to secrete proteases and anticoagulants that allow for early access to the maternal blood supply; combined actions of the cytotrophoblasts and the syncytium enable maternal blood to sweep over and bathe the syncytium; the blood is collected by lacunae that funnel it to the underlying cytotrophoblasts

Front 4

describe the role of the chorionic villi in establishing uteroplacental circulation

Back 4

the dual capacity of the cytotrophoblasts to attach, breakdown, and advance, enables the endometrial invasion to be aggressive, yet controlled; proteases and anticoagulants also enable the cytotrophoblasts to invade decidual blood vessels, and thereby tap into the maternal blood supply
Superficial endometrial capillaries and veins are invaded 1st, followed by the arterioles and then the uterine spiral arteries; as this proceeds the arterial wall undergoes degeneration as the cytotrophoblasts migrate into the arterial lumen; midway through the 2nd trimester, most of the spiral arteries are invaded in this manner

Front 5

describe the maturation of the chorionic villi during the establishment of uteroplacental circulation

Back 5

12 days after fertilization, the chorionic villi appear as a solid column of cytotrophoblastic cells (primary villi); mesenchymal infiltration of the primary villi transform them into secondary villi; angiogenesis taking place in the mesenchymal core results in tertiary villi
17 days after fertilization, fetal-placental circulation is first established; continued maturation of the chorionic villi leads to repeated branching, resulting in a placental cotyledon (lobe); each placental lobe is supplied w/ a branch of both the chorionic artery and vein

Front 6

describe circulation in the mature placenta

Back 6

5 weeks after implantation, the uteroplacental circulation is well-established; the fetal heart pumpdes blood into the chorionic villi and fetal tissues
Fetal blood is transported to and from the placenta via the umbilical artery and vein in the umbilical cord; deoxygenated fetal blood flows into the placenta via the umbilical arteries, and oxygenated blood returns from the placenta via the umbilical vein
Umbilical vessels branch to form the chorion artery and vein, which run between the chorion laeve and amnion; the chorionic vessels send branches to individual placental lobes
Maternal blood from the spiral arteries enters into the intervillous spaces; the in-coming arterial blood displaces venous blood into the endometrial veins

Front 7

Describe gestational trophoblastic disease (GTD)

Back 7

involves complete and partial hydatiform moles (molar pregnancies) and other neoplasms (choriocarcinoma, placental-site trophoblastic tumors)
Complete molar pregnancies are most common, and occur w/ the highest incidence in women of southeast asian descent; individuals present w/ uterine bleeding, intense nausea and vomiting (due to hypersecretion of hCG), electrolyte imbalances, decidual edema, trophoblast hyperplasia and chorionic swelling
Complete molar pregnancies are devoid of fetal tissue; partial molar pregnancy may contain a fetus w/ congenital malformations

Front 8

describe how O2 and CO2 exchange works in the placenta

Back 8

The cell membrane of the cytotrophoblast is the site of transfer between the intravillous spaces; fetal capillaries are a site of exchange from the intravillous space into the fetal blood
O2 transfer-depends on the rate of blood flow; the fetal cardiovascular system compensates for the low PO2 of fetal blood by having a higher CO per unit body weight, higher Hb concentration, and a higher O2-carrying capacity of fetal Hb
CO2 transfer-accomplished by simple diffusion; the driving force favors the movement of CO2 from the fetal to the maternal circulation, due to greater affinity of maternal blood for CO2, and a slight elevation in respiratory activity in the pregnant female

Front 9

describe how nutrients, drugs, and microorganisms are exchanged in the placenta

Back 9

nutrients-accomplished via simple diffusion, facilitated diffusion or active transport
drugs-thalidomide, heroin, cocaine, nicotine, aspirin, and alcohol can traverse the placenta and reach the fetus
viruses/microorganisms-rubella, varicella, cytomegalovirus, and HIV can cross the placenta and infect the fetus; bacteria (treponemes and tb), and protozoa (toxoplasma and plasmodium) can cause fetal infection

Front 10

describe how immunocompatability is maintained b/t maternal in fetal tissue

Back 10

1. trophoblast expression of HLA-G: HLA-G is expressed by cytotrophoblasts; it's recognized as “self” by suppressor T cells, so it does not evoke an immune response
2. Fas/Fas ligand interactions-placental surface expresses the Fas ligand that binds to the Fas receptor of T lymphocytes to trigger lymphocyte apoptosis
3. uterine large granular lymphocytes (LGLs)-from the natural killer (NK) cell lineage, they peak at implantation
Activated LGLs persist in the decidua during early stages of pregnancy, and secrete large granulocyte/macrophage-colony stimulating factor (GM-CSF) that helps regulate trophoblast invasion
4. placental indoleamine 2,3-dioxygenase (IDO)-is expressed by the fetal portion of the placenta, and catalyzes the conversion of tryptophan to kynurenine, lowering placental tryptophan concentrations; this suppresses maternal T cell-mediated immune activity directed against the developing fetus (minimizes possibility of fetal rejection)

Front 11

describe the function of human chorionic gonadotropin (hCG) in pregnancy

Back 11

Secreted by the syncytium early in pregnancy; early indicator of pregnancy; blood levels peak midway through the 1st trimester
Maintains the corpus luteum to ensure continued output of estrogen and progesterone necessary for the maintenance of pregnancy; the corpus luteum persists for 10 weeks until the placenta begins to synthesize and secrete these hormones
hCG stimulates testosterone secretion from the fetal testes during sexual differentiation

Front 12

describe the function of estrogen (estradiol) in pregnancy

Back 12

fetoplacental unit-the placental synthesis and secretion of estrogen requires interaction b/t the placenta and fetus; he fetal adrenal cortex produces dehydroepiandrosterone (DHEA); some DHEA is 16a-hydroxylated by the fetal liver; 16a-Hydroxy-DHEA is aromatized in the syncytium to form estriol
functions-estrogen stimulates the myometrial growth in preparation for the uterine contractions during parturition, and promotes duct development in the mammary gland in preparation for lactation; levels rise gradually throughout gestation

Front 13

describe the function of progesterone in pregnancy

Back 13

Placental progesterone is synthesized from cholesterol at a rate dependent on the number of LDL receptors on the syncytium membrane; levels increase gradually throughout the gestational period
functions-progesterone suppresses myometrial excitability, and maintains the cervical mucus plug; helps prepare the breast for lactation by stimulating the development of the secretory milk glands

Front 14

describe the function of human chorionic somatomammotropin (hCS; placental lactogen) in pregancy

Back 14

The syncytium secretes this hormone; concentrations of hCS rise steadily until near term, but the hCS mRNA levels per unit placental weight remain fairly constant
functions-hCS helps promote the function of the mammary glands for impending lactation; decreases maternal glucose utilization and increases lipolysis to divert greater quantities of glucose and free fatty acids to the fetus

Front 15

describe the function of parathyroid hormone-related peptide (PTHrp) in pregnancy

Back 15

PTHrp is expressed in the placenta (especially abundant in the reproductive system); placental expression is regulated by circulating Ca2+ concentrations
functions-increases maternal Ca2+ levels in plasma by causing dissolution of maternal bone, thereby providing a source for the calcification of fetal bones

Front 16

describe the function of relaxin in pregancy

Back 16

Relaxin is expressed in the corpus luteum, the decidua, and the placenta
Relaxin is composed of 2 polypeptide chains derived from the same preprorelaxin precursor molecule (H1 and H2); most tissues express both isoforms (corpus luteum expresses only H2)
functions-acts in concert w/ progesterone to inhibit uterine myometrial contractility; near term, relaxin works w/ PGs to cause the dissociation of cervical collagen fibers to increase cervical pliability, and loosens the CT in b/t the pelvic bones in preparation for parturition

Front 17

describe the function of corticotropin-releasing hormone (CRH) in pregnancy

Back 17

CRH is expressed in the syncytium, chorion laeve, amnion and decidua; the concentration in maternal plasma increases as pregnancy pregresses (15X higher by the 3rd trimester)
During the last 5-6 weeks of gestation, CRH increases sharply
functions-serves as a “placental clock” that ticks out the gestational length of time until parturition

Front 18

describe the function of prostaglandins (PGs) and leukotrienes in pregnancy

Back 18

locally produced in the endometrium, myometrium, decidua and placenta by enzymatic conversion of arachidonic acid via cyclooxygenase (PGs) and lipoxygenase (leukotrienes
Both PGs and leukotrienes induce the formation of the decidua from the endometrium to facilitate implantation; they cause myometrial smooth muscle contraction and cervical ripening

Front 19

describe uterine and breast changes during pregnancy

Back 19

The uterus increases in weight 20X, due to myometrial hypertrophy, accumulation of collagen fibrils and increased elastic tissue; uterine vascularization and innervation are increased
Breast enlargement after the 2nd month of gestation is associated w/ increased vascularization and pigmentation of the nipples; the breasts begin to develop the capacity to produce colostrum; elevated, hypertrophied sebacious glands (glands of Montgomery) are scattered along the areolar surface

Front 20

describe the changes in blood volume in pregnancy

Back 20

Maternal blood volume increases 30-45% to help the mother meet the increased demands of the growing placental and fetal masses, and to counteract impaired venous return; It safeguards against blood loss that may occur w/ parturition
The hypervolemia is due to increases in both plasma volume and RBC count; hematocrit and Hb concentrations decrease slightly during pregnancy
Activation of the coagulation system causes a 50% increase in plasma fibrinogen concentrations

Front 21

describe the cardiovascular changes that occur in pregnancy

Back 21

Cardiac output increases 50%; the 1st half of pregnancy has increased stroke volume, while the latter half has an elevated heart rate; impaired venous return in late pregnancy can decrease CO due to periodic occlusion of the IVC by the gravid uterus; leads to episodes of dizziness, lightheadedness or syncope referred (IVC syndrome)
Progesterone causes vasodilation that leads to decreased peripheral vascular resistance; blood pressure is decreased for the 1st 6 months of pregnancy, but returns to normal by term; elevated BP may indicate preeclampsia
Preeclampsia occurs in the 2nd half of pregnancy; is precipitated by ingestion of a high-fat diet; patients present w/ peripheral edema and exhibit proteinuria; decreased production of PGs E1 & E2 precede the onset of the HTN

Front 22

describe the renal changes that occur in pregnancy

Back 22

renal plasma flow increases 75%, and GFR increases 50%), causing increasing urinary output
Progesterone induces smooth muscle relaxation that causes dilation of the collecting system and decreases bladder tone
Creatine clearance is increased, and Na is presented to the kidneys at a greater rate; this reduces the plasma concentrations of creatinine and Na, and decreases plasma osmolarity; this is compensated for by increased levels of aldosterone, and the renin-angiotensin system; in pregnancies associated w/ a preexisting HTN, these elevations may cause complications
The elevated GFR also increases the glucose load, and leads to increased glucose excretion

Front 23

describe gastrointestinal changes during pregnanct

Back 23

In the 1st 2 months of pregnancy there is an increased incidence of nausea and vomiting (morning sickness) due to elevated levels of hCG, progesterone, and relaxation of gastric smooth muscle
Symptoms of morning sickness persisting into the 2nd trimester (weight loss, ketonemia, or reductions in circulating levels of electrolytes) are indicative of hyperemesis gravidarum; this correlates w/ elevated hCG, estradiol, and prolactin concentrations and hyperthyroidism
Many women experience strong, unusual dietary cravings called pica
Pregnancy decreases GI motility due to progesterone-induced relaxation of GI smooth muscle, and increases transit time through the stomach and small intestine 15-30% by the 2nd trimester; heartburn is often experienced due to gastric reflux associated w/ reductions in both rate of gastric emptying and lower esophageal sphincter tone
Constipation is due to reduced transit and increased H2O absorption; the rate of gallbladder emptying is also reduced, which increases the incidence of gallstones
Changes in liver function are increased cholesterol, alkaline phosphatase, fibrinogen and steroid hormone binding proteins, and decreased albumin in the plasma

Front 24

describe respiratory changes in during pregnancy

Back 24

Net respiratory activity is increased during pregnancy to meet the demand for increased O2 consumption; maternal respiratory rate is unaffected, but increases in tidal volume, minute ventilatory volume and minute O2 uptake are occur; the residual volume is decreased, airway conductance is increased, and total pulmonary resistance decreased
The pregnancy-induced increase in tidal volume results in a slight decrease in the Pco2 of maternal blood

Front 25

describe the metabolic changes that occur during pregnancy

Back 25

Significant H2O retention is observed that decreases plasma osmolality; at term, the mother carries additional H2O and protein
Carbohydrate metabolism is characterized by mild fasting hypoglycemia, postprandial hyperglycemia, and hyperinsulinemia; the sustained postprandial increase in glucose levels is attributed to a peripheral resistance to insulin; the compromised effectiveness of insulin are due to the diabetogenic actions of hCS; these pregnancy-induced alterations in carbohydrate metabolism allow for a continual supply of glucose for fetal consumption
Plasma concentrations of LDLs and HDLs peak during the 2nd trimester due to rising concentrations of progesterone (LDL) and estrogen (HDL)
The maternal demand for Fe often outweighs that available from the normal diet; if Fe is not supplemented during the 2nd half of pregnancy, then blood levels decline
Ca and Mg concentrations in plasma are reduced due to decreased levels of plasma binding proteins, enabling more of these cations to go into the fetal circulation; plasma Ca levels are tightly regulated due to the effects of PTHrp

Front 26

describe the dilation of the cervical canal in parturition

Back 26

As parturition approaches, the cervix begins to soften, which allows it dilate in response to the head of the fetus pushing against it
Relaxin softens the cervix and pelvis, acting synergistically w/ PGs that induce the release of proteolytic enzymes and degrade the cervical collagen matrix

Front 27

describe uterine myometrial contractions

Back 27

During the 3rd trimester, the progressive increase in uterine myometrial excitability leads to Braxton-Hicks contractions; at the onset of labor, rhythmic and coordinated contractions are experienced; as these increase in strength and frequency, they push the fetus against the cervix to cause cervical dilation; as the cervical opening widens, the myometrial contractions force the fetus through the cervical canal

Front 28

describe the role of estrogen in uterine myometrial contractions

Back 28

Estrogen promotes myometrial growth and contractility by promoting the synthesis of connexins and the formation of gap jxns b/t myometrial smooth muscle cells; this enables the myometrium to function as a syncytium
Estrogen also increases the density of myometrial oxytocin receptors

Front 29

describe the role of CRH in uterine myometrial contractions

Back 29

Placental CRH stimulates the secretion of ACTH from the fetal anterior pituitary; ACTH then stimulates the production of DHEA and cortisol from the adrenal cortex; increased DHEA levels help drive the placental production of estrogen during late pregnancy, which then sensitizes the uterine myometrium in preparation for parturition
The cortisol produced by the fetal adrenal gland stimulates surfactant production, which enables lung expansion and allows the developing fetal lung to work more efficiently
Activation of the maternal stress axis helps the expectant mother cope w/ stress of pregnancy and impending parturition

Front 30

describe the role of oxytocin in uterine myometrial contractions

Back 30

Oxytocin increases PG secretion that potentiates the oxytocin-induced contractions; the near-term myometrial responsiveness to oxytocin is 100X greater than in the non-pregnant myometrium due to the estrogen-induced upregulation of myometrial oxytocin receptors
During labor, stimulation of receptors in the cervix and vagina causes an increase in oxytocin secretion; myometrial contractions progressively increase in strength, frequency, and duration over the course of labor until the fetus is expelled

Front 31

describe the stages of labor

Back 31

cervical dilation-the amnionic membrane ruptures (water breaking); cervix dilates up to 10cm, wide enough to accommodate the baby’s head; this is the longest stage (few hours to over 24 hours)
delivery of the baby-begins once cervical dilation is sufficient to allow fetal passage through the cervix and vagina; vaginal stretch receptors trigger a neural reflex that elicits contraction of the abdominal muscles, which enchances delivery once the pregnant mother can voluntarily control them; this stage lasts 30-90 min
delivery of the placenta (afterbirth)-a 2nd wave of uterine contractions causes placental detachment from the myometrium; the delivery of the afterbirth constitutes the final stage of labor, and occurs in 15-30 minutes after the delivery of the baby

Front 32

describe involution

Back 32

The gradual restoration of pre-gestational uterine size is called involution; due to the postpartum reduction in estrogen and progesterone levels; the vestigial endometrial remnants produce a vaginal discharge called lochia; it takes 4-6 weeks for this process to be completed

Front 33

describe postpartum depression

Back 33

Altered activity of the stress axis is implicated in clinical depression; a CRH withdrawal syndrome results from the decline in CRH concentrations following parturition
During late pregnancy the elevated CRH concentrations increase maternal concentrations of ACTH and cortisol that cause inhibition of the stress axis via cortisol-induced negative feedback; as a result, depression occurs during this latency to recovery of the normal function of the stress axis