Functions of the Placenta (PDF)

Functions of the placenta 1- Diffusion of oxygen from the maternal blood to the fetal blood. Near the end of pregnancy, PO2 in the mother’s blood is 50 mmHg and in the fetal blood is 30 mmHg. Thus, the pressure gradient for diffusion of O 2 through the placenta is about 20 mmHg. This low PO2 can al...

Functions of the placenta 1- Diffusion of oxygen from the maternal blood to the fetal blood. Near the end of pregnancy, PO2 in the mother’s blood is 50 mmHg and in the fetal blood is 30 mmHg. Thus, the pressure gradient for diffusion of O 2 through the placenta is about 20 mmHg. This low PO2 can allow the fetal blood to transport as much O2 to the fetal tissue due to: a) Fetal HB can carry 20-50% more O2 than maternal HB can. b) HB concentration of fetal blood is about 50% greater than that of the mother. c) Bohr effect: the fetal blood entering the placenta carries larger amount of CO2. Loss of CO2 makes the fetal blood more alkaline with increasing combining capacity of its HB for O2. Whereas, the increased CO2 in the maternal blood makes it more acidic with decreased the combining capacity of its HB for O2. 2- Diffusion of carbon dioxide from fetal blood to maternal blood by simple diffusion. 3- Transport of nutrients - Glucose is transported by facilitated diffusion. - Amino acids are actively transported across the placenta. - Fats directly transported from mother to fetus in early pregnancy but synthesized in the fetus later in pregnancy. 4- Transport of electrolytes: Na+, K+, Cl- transported by simple diffusion. Ca+2, Ph, iron transported by active transport. 5- Excretion of waste products as urea, uric acid and creatinine from fetal to the maternal blood. 6- Protective function - Placenta acts as a barrier against the transfer of certain harmful materials into the fetus. Also, IgG and antitoxins cross the placenta and give a passive immunity to the fetus. - However, some drugs and viruses cross the placenta and may cause fetal malformation. Also, Rh agglutinin can pass through the placenta into the fetus. 7- Endocrine functions A) Human chorionic gonadotropin (hCG) - It is a glycoprotein secreted by trophoblast after fertilization, peak of secretion occurs about 8th week. - It can be measured in blood as early as 6 days, and in urine as early as 14 days after conception. - The presence of hCG in blood and urine samples is a reliable indicator of pregnancy. Functions 1- Maintenance of the function of corpus luteum (CL). It prevents degeneration of CL and stimulates it to secrete estrogen and progesterone which, in turn, stimulate continual growth of endometrium. 2- Promotes implantation and helps growth of trophoblasts and placental development 3- Stimulates leydig cells of male fetus to produce testosterone. So, help in development of male sex organs. 4- Suppress maternal immune function and reduces the possibility of fetus immune-rejection. B- Estrogen The placenta does not able to synthesize estrogen hormone. Estrogen hormone synthesis requires a complex interaction between the placenta and the fetus. Because both fetal and placental tissues participate in this biosynthetic pathway, estrogen is said to be produced by the fetoplacental unit. Fetoplacental unit - The placenta can convert the androgen hormone produced by the fetal adrenal cortex, dehydroepiandrosterone (DHEA) into estrogen. - The placenta extracts DHEA and 16 (OH) DHEA from the fetal blood and converts them into estrogen, which then secrets into the maternal blood. The primary estrogen synthesized by this unit is estriol, in contrast to the main estrogen produced by the ovaries, estradiol. Functions of estrogen during pregnancy 1- Enlargement of the mother’s uterus and external genitalia. 2- Promotes development of the ductal system within the mother’s breast. 3- Relax pelvic ligaments to facilitate labor. C- Progesterone In the case of progesterone, the placenta can synthesize this hormone soon after implantation. Functions of progesterone during pregnancy 1- Increase the secretion of fallopian tubes and the uterus to provide nutrition of the fertilized ovum before implantation. 2- Development of decidual cells in the uterine endometrium which help implantation and nutrition of early embryo. 3- Maintenance of pregnancy by inhibiting the contractility of the uterus to avoid abortion. 4- Promoting formation of mucous plug in the cervical canal to prevent vaginal contaminants from reaching uterus. 5- Development of the lobule-alveolar system of the breast to prepare breast for lactation. D- Relaxin It is a polypeptide hormone secreted by the corpus luteum and placenta. Functions 1- Relaxes the ligaments of pubic symphysis and other pelvic joints. 2- Softens and dilate the cervix during pregnancy. Thus, it facilitates delivery. 3- Inhibits uterine contractions. E- Human chorionic somatomammotropin (hCS)- Human placental lactogen (hPL) It is a protein hormone secreted by the placenta at 5th weeks of pregnancy. It is lactogenic; preparing the breast glands for lactation. hCS acts as a maternal growth hormone of pregnancy (it has a GH like actions) because: a) It stimulates protein deposition in the tissues. b) It causes retention of nitrogen, potassium and calcium. c) It stimulates lipolysis and decreases glucose utilization. These actions direct glucose to the fetus while fatty acids are used by the mother as a source of energy. Physiological changes in different body systems during pregnancy 1- Osmoregulation Pregnancy is a state of chronic volume overload and has many features similar to those of congestive heart failure, including edema and polyuria. The fetus, placenta, and amniotic fluid contribute about half of the 6- to 8-L increase in the woman’s total body water. 2- Urinary System - Positioning of the fetus can lead to decreased bladder capacity and increased urinary frequency and incontinence. - Volume overload dilutes the serum levels of blood urea nitrogen (BUN), creatinine, and uric acid, and increases the effective renal plasma flow and GFR. - The renal tubular absorptive capacity is increased. 3- Cardiovascular System - Increased heart rate (HR) and stroke volume (SV) result in a 30–50% increase in cardiac output. - Blood pressure (BP) decreases secondary to progesterone acting on smooth muscle to decrease systemic vascular resistance. By the third trimester, BP returns to baseline. - Peripheral venous distension progressively increases to term. - A low-grade systolic flow murmur and mild left ventricular hypertrophy are other normal physiologic changes seen during pregnancy. 4-Hematological System - Blood volume increases about 50%, plasma expands earlier than RBC mass, accelerating the development of physiologic anemia. - Due to increased fibrinogen, the mother is in a hypercoagulable state 5-Respiratory System - Pregnancy results in elevation of the diaphragm, which decreases the residual volume. - The total lung capacity (TLC) decreases only slightly but the inspiratory capacity is increased. - The tidal volume (TV) increases to allow for increased minute ventilation (MV) and chronic hyperventilation. - Vital capacity is unchanged. 6-Digestive system - Most changes of the digestive system are side effects of hemodilution, estrogen, and progesterone. - Albumin and total protein levels appear decreased due to volume overload. - Increase Na+ and water absorption in the large intestine. - Progesterone decreases sphincter tone and reduces small intestine motility, leading to constipation. - Progesterone delays gall bladder emptying, and estrogen and progesterone promote saturation of bile with cholesterol which favor formation of gallstones. - Smooth muscle relaxation of the lower esophageal sphincter leads to gastroesophageal reflux disease and nausea. 7-Endocrine system - Human placental lactogen induces maternal insulin resistance to ensure continued transport of nutrients from mother to fetus. This leads to glucose intolerance (fasting hypoglycemia and postprandial hyperglycemia in the mother). Decreased body response to insulin results in pancreatic β-cell hypertrophy, hyperinsulinemia and an increased risk of gestational diabetes. - Triglycerides (TGs), high- and low-density lipoproteins (HDLs and LDLs), and total cholesterol levels all increase during pregnancy, as they are necessary precursors for steroidogenesis in the maternal adrenal glands. - The pituitary gland enlarges and increases its secretion of prolactin. 8-Immune system - Progesterone reduces the immune response, to prevent rejection of the “foreign” fetus. The pregnant uterus is also utilizing a number of sophisticated mechanisms to promote tolerance of the fetus. - Estrogen and cortisol cause a progressive rise in white blood cell count mostly polymorphonuclear leukocytes. Parturition (Labor) Also called childbirth; the process of delivering the baby and the placenta from the uterus to the outside world. The onset of labor is marked by regular, painful uterine contractions and progressive dilation of the cervix. Duration of pregnancy: The length of pregnancy is about 270 days from Conception or 284 days from the last menses. ❖ Mechanism of parturition: (Hormonal control) The nature of the trigger for parturition is poorly understood but it is believed that the fetus plays a role in determining the time of its birth and involves mechanisms in both the maternal and fetal nervous and endocrine systems.  Fetal cortisol initiates a switch in the placenta away from progesterone synthesis to estrogen synthesis in the last few days of pregnancy and the resulting increase in cortisol hastens the maturation of the respiratory system. Estrogens, together with oxytocin and prostaglandin F2A (PGF2A), increase the contractility of the myometrium to bring about delivery. Key mediators of parturition: Figure (1) Oxytocin is a peptide hormone synthesized in the hypothalamus and released from the posterior pituitary which stimulates uterine contractions during labor, both directly and through the action of prostaglandins. Oxytocin secretion is stimulated by uterine distension and vaginal stimulation as the fetal head descends which, in turn, stimulates more oxytocin release (positive feedback—the Ferguson reflex), also, is called the fetal ejection reflex that is the neuroendocrine reflex. The number of myometrium oxytocin receptors increase in late pregnancy as progesterone levels fall. Prostaglandins (PGF2) (stimulated by oxytocin) is synthesized by the myometrium and stimulates muscle contraction and cervical ripening (cervix softens and dilates). Labour can be induced at term using vaginal pessaries containing PGF2A. Changes in the effective oestrogen/progesterone ratio (Figure 3): The rising level of estrogen (change estrogen to progesterone ratio) cause: ▪ Increases oxytocin receptors in the uterus ▪ Overcome the inhibitory effect of progesterone on uterine contractions. ▪ Increases the number of gap junctions between myometrial  cells, ensuring a rapid spread of contractions. ▪ Increases production of prostaglandins (PGF2) which in turn cause uterine contractions. ❖ Premature and delayed parturition: ✓ Normal ‘term’ of pregnancy in humans is 40 weeks (37 to 42 weeks) after the last menstrual period. Both pre-term and post-term labor are hazardous. Pre-term because the fetus is not yet prepared for extra-uterine life and post-term because continued fetal growth and placental insufficiency pose problems for both delivery and fetal nutrition. ✓ Toward the end of pregnancy, several changes must occur in the fetus in preparation for postnatal life. Most of these are induced by the secretion of glucocorticoids which increased markedly towards term. Such changes include: - Production of surfactant in the lungs to allow lung expansion when air is first breathed. - Changes to gut and liver enzymes to allow the fetus to metabolize its postnatal milk diet. ✓ If premature labor occurs prior to the 34-week gestational age, glucocorticoids may also be administered to the mother to hasten fetal lung development, increase fetal alveolar cell surfactant production, and lower the possibility of infant respiratory distress syndrome at birth. ❖ Stages of labor Labor consists of three stages: 1st (Dilatation) stage: - This is the longest stage, lasting 8 to 24 hours in a primipara (a woman giving birth for the first time) but as little as a few minutes in a multipara (a woman who has previously given birth). - Started by labor pain and ends by full cervical dilation. The pain of labor is mainly due to ischemia of the myometrium muscle, which hurts when deprived of blood. Each labor contraction temporarily restricts uterine circulation. As the fetus enters the vaginal canal, the pain becomes stronger because of increased stretching of the cervix, vagina, and perineum and sometimes the tearing of vaginal tissue. - Uterine contractions become progressively stronger to propel the fetus down the birth canal. At the same time, the amniotic sac ruptures (waters break). 2nd (Expulsion) stage: started by full cervical dilation and ends by delivery of the baby. It usually lasts 40–60 min. 3rd (Placental) stage: the time from birth to the delivery of the placenta.. It usually lasts 15 minutes after birth of infant. All placental fragments should be removed to avoid postpartum bleeding  Hormones controlling breast development/milk formation and ejection during different developmental stages Stage Hormones Functions/effects No hormones ------------------ At birth very few acini At puberty A. Estrogens ❑ Growth & branching of the ductal system of the breasts, ❑ Increasing the stroma of the breasts, ❑ Deposition of large quantities of fat in the stroma (increasing the size of breasts). B. Progesterone ❖ Growth of the breast lobules &acini (still immature) During 1.Estrogens ❑ The same as at puberty pregnancy 2. Progesterone ❖ Additional growth of the breast lobules, ❖ budding of alveoli and ❖ development of secretory characteristics in the cells of the alveoli. 3. Prolactin ❑ Growth of ductal system & 4. Human placental ❑ Milk production lactogen After labor/ 1. Prolactin ❖ Milk production during lactation 2. Oxytocin ❑ Milk ejection 3. growth ❖ These hormones are necessary to provide hormone, the amino acids, fatty acids, glucose, 4. cortisol, and calcium required for milk 5. Parathyroid formation. hormone, 6. insulin. Growth of mammary tissue is stimulated by estrogen and progesterone. However, for these steroids to stimulate maximum growth, prolactin, growth hormone, and cortisol also must be present. Prolactin Site of secretion: anterior pituitary gland (lactotrophs). Functions: 1. It stimulates the growth and the development of mammary gland ducts. 2. It stimulates the development and growth of secretory alveoli in the breast. 3. It initiates and maintains lactation (milk formation/production). Factors affecting/controlling prolactin secretion I. Stimuli that increases prolactin secretion 1. Thyroid stimulating hormone (TSH) from the hypothalamus. 2. Pregnancy: high Estrogen increases the production of prolactin but antagonizes the milk-promoting effect. 3. Suckling (breast feeding). 4. Exercise, sleep. II. Stimuli that decreases prolactin secretion ❑ Prolactin inhibiting hormone (PIH/ dopamine) from the arcuate nucleus of the hypothalamus and transported through the hypothalamic-hypophysial portal system to the anterior pituitary gland to act on the D2 receptors of lactotrophs; ❑ dopamine agonist can be used to inhibit lactation. Note: ❖ The anterior pituitary secretion of prolactin is controlled mainly by an inhibitory factor called "prolactin inhibitory hormone" or dopamine. ❖ The major physiological stimulus to prolactin secretion is suckling. Oxytocin and Milk ejection/ (milk let-down mechanism) ❑ Stimuli: suckling of the nipple. ❑ Receptors: touch receptors in the nipple. ❑ Center: the oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus, which increases Oxytocin synthesis and secretion. ❑ Response: contraction of myoepithelial cells lining the alveoli and the duct walls. Thus, pre-formed milk expressed/ejected from the alveoli into the ducts of the breast so that the baby can obtain it by suckling.  ❖ The reflex becomes conditioned after a short time, so that the sound or the sight of the infant can cause milk let-down to start even before suckling begins. N.B. Suckling not only evokes reflex oxytocin release and milk ejection, but it also maintains and augments the secretion of milk because of the stimulation of prolactin secretion produced by suckling. Initiation of Lactation (lactogenesis) after Delivery ❑ During pregnancy, prolactin and estrogen synergize in producing breast growth. However, the high levels of plasma estrogen during pregnancy greatly increase prolactin secretion, but milk synthesis does not occur WHY?? Because high levels of estrogen and progesterone antagonize/block the milk-producing effect of prolactin on the breast. Thus, no more than a few milliliters of fluid are secreted each day until after the baby is born. ❑ After expulsion of the placenta at parturition, the levels of circulating estrogens and progesterone abruptly decline. The sudden loss of both estrogen and progesterone secretion from the placenta withdrawing the block on milk synthesis and allows the lactogenic effect of prolactin to assume its natural milk-promoting role Maintenance of lactation ❑ Few weeks after birth of the baby: The basal level of prolactin secretion returns to the nonpregnant level. ❑ Breastfeeding: each time the mother breastfeeds her baby, nervous signals from the nipples are transmitted to the hypothalamus to cause a 10- to 20-fold surge in prolactin secretion that lasts for about 1 hour. This prolactin acts on the mother’s breasts to keep the mammary glands secreting milk into the alveoli for the subsequent nursing periods. Milk production is maintained by continued prolactin secretion so long as suckling continues/ Suckling is required to maintain lactation. ❑ Hypothalamic or pituitary damage or if nursing does not continue: Prolactin surge is absent or blocked as a result of, the breasts lose their ability to produce milk within 1 week or so. However, milk production can continue for several years if the child continues to suckle. Effect of Lactation on Menstrual Cycle ❑ Women who nurse regularly have amenorrhea for 25 to 30 wk and nursing has long  been known to be an important, if only partly effective, method of birth control. Mechanism: ❑ Increased prolactin inhibits the pulsatile release of GnRH and in turn suppresses formation of the pituitary GnH (LH and FSH). This leads to inhibition of ovulation, decreased estrogens and progesterone (lactation amenorrhea). Beneficial effects of lactation/breast feeding 1. Passive immunity: breast milk contains maternal immunoglobulin (IGA), macrophages, and lymphocytes; Breast milk reduces infant infections. 2. Breast milk decreases the risk for a child to develop asthma, allergies, diabetes mellitus, and obesity. 3. Breast feeding reduces the risk of breast and ovarian cancer 4. Breast feeding facilitates mother-child bonding. Suckling stimulates receptors in the mother’s nipples that send signals to the hypothalamus resulting in: 1. Oxytocin synthesis and secretion are increased (milk ejection). 2. The release of dopamine by the hypothalamus is inhibited. This removes a chronic inhibition on prolactin secretion resulting in milk production each time the baby suckles. 3. The secretion of GnRH into the hypophyseal portal vessels is inhibited resulting in lactational amenorrhea. For the suckling stimulus to inhibit GnRH secretion completely, the stimulus must be prolonged and frequent.