1 Physiology of Pregnancy,Parturition,and Lactation
2 Oogenesis Ovum formation by meiosis in follicles of ovariesOogonia in fetal period in females rapidly divide and transform into primary oocytes in primordial follicles (~ 2 million by birth) Primary oocytes begin meiosis I, but arrest in prophase I Starting at puberty, "one" follicle is chosen each month (from ~ 250,000 remaining) to complete meiosis I, resulting in a secondary oocyte The secondary oocyte begins meiosis II, but arrests in metaphase II The secondary oocyte is ovulated into uterine tube; if fertilization occurs, following sperm entry, meiosis II is completed, forming the ovum and another polar body
3 Entry of the Ovum into the Fallopian Tube (Uterine Tube)After ovulation occurs, the ovum with the granulosa cells (the corona radiata) is expelled into the peritoneal cavity. It enters the fallopian tube by passing through the fimbriated ends of each fallopian which fall around the ovaries. What helps the movement of ovum; The inner surface of the fimbriated ends is lined with ciliated epithelium, the cilia are activated by estrogen, which causes them to beat toward the opening, or ostium, of the involved fallopian tube. Slow fluid current flowing toward the ostium Ova can even enter the opposite fallopian tube.
4 Fertilization of the OvumFew sperms reach the ampullae of the fallopian tubes near the ovarian ends of the tubes during the intercourse . Transport of the sperm is aided by: contractions of the uterus and fallopian tubes stimulated by prostaglandins in the male seminal fluid oxytocin released from the posterior pituitary gland of the female during her orgasm. Site of fertilization of the ovum: the ampulla of one of the fallopian tubes.
5 Fertilization of the OvumSperm first penetrates the multiple layers of granulosa cells (the corona radiata) Then sperm binds to and penetrates the zona pellucida. Once a sperm has entered the ovum, the 2ndy oocyte divides to form the mature ovum (a second polar body is expelled). The fertilized ovum contain 23 unpaired chromosomes of the male pronucleus & the 23 unpaired chromosomes of the female pronucleus (so a complete set of 46 chromosomes)
6 Transport of the Fertilized Ovum in the Fallopian TubeAfter fertilization, 3 to 5 days is required for transport of the fertilized ovum through the remainder of the fallopian tube into the cavity of the uterus Transport is effected by A weak fluid current in the tube resulting from epithelial secretion. Beating of the ciliated epithelium that lines the tube toward the uterus. Weak contractions of the fallopian tube.
7 Transport of the Fertilized Ovum in the Fallopian TubeThe isthmus of the fallopian tube remains spastically contracted for about the first 3 days after ovulation. Progesterone secreted by the ovarian corpus luteum increases and activates progesterone receptors, leading to isthmus relaxation allowing entry of the ovum into the uterus. During fallopian transport, several stages of cell division occur forming the blastocyst Fallopian tube secretory cells produce large quantities of secretions used for the nutrition of the developing blastocyst.
8 Implantation of the Blastocyst in the UterusBlastocyst remains in the uterine cavity an additional 1 to 3 days before it implants in the endometrium; During this time, the blastocyst obtains its nutrition from the uterine endometrial secretions, called "uterine milk" Implantation normally occurs on about the 5th – 7th day after ovulation. Implantation results from the action (invasion) of trophoblast cells over the surface of the blastocyst. These cells secrete proteolytic enzymes that digest and liquefy uterine endometrium cells. Some of the fluid and nutrients released are utilized for blastocyst growth. Trophoblast cells , uterine endometrium cells, & other blastocyct cells form the placenta and the various membranes of pregnancy.
9 Early Nutrition of the Embryoprogesterone aids in converting the endometrial stromal cells into large swollen cells containing extra quantities of glycogen, proteins, lipids, and even some minerals necessary for development of the conceptus (the embryo and its adjacent parts or associated membranes). Decidual cells: The swollen endometrial cells (storing nutrients) Decidua: the total mass of cells Nutrition sources: The trophoblast cells invade the decidua, digesting it, the stored nutrients in the decidua are used by the growing embryo Decidual cells are the only source of nutrients to the embryo During the first week after implantation (continues up to 8 weeks) The placenta begins to provide nutrition after about the 16th day after fertilization (~ 1 week after implantation).
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11 Function of the PlacentaTrophoblastic cords attach to endometrium (form villi) Fetal blood capillaries grow into the trophoblastic cords Maternal blood sinuses develop around the outsides of the trophoblastic cords (villi) Villi, carrying fetal blood, are surrounded by sinuses that contain maternal blood. So, placenta is composed of fetal components & maternal components Nutrients and other substances pass through this placental membrane mainly by diffusion
12 Permeability of the PlacentaThe major function of the placenta is to provide for diffusion of foodstuffs and oxygen from the mother's blood into the fetus's blood and diffusion of excretory products from the fetus back into the mother. In early pregnancy, the placental membrane not fully developed (still thick & small surface area), So, permeability is low. In later pregnancy, the permeability increases (thinning of the membrane & expansion of surface area)
13 Diffusion of Oxygen Through the Placental MembraneDissolved O2 passes into fetal blood by simple diffusion from maternal sinuses Maternal blood Mean PO2: 50 mmHg Fetal blood mean PO2: 30 mmHg The mean pressure gradient for diffusion of O2 through the placental membrane: 20 mmHg. This low fetal Po2 is still capable of supplying adequate oxygen to the fetal tissues; Hemoglobin of the fetus is mainly fetal hemoglobin, (bind oxygen with greater affinity than the adult form)
14 Hemoglobin concentration of fetal blood is about 50% greater than that of the motherBohr effect; (hemoglobin can carry more oxygen at a low Pco2 than it can at a high Pco2), the double Bohr effect.
15 Diffusion of CO2, foodstuffs, & wastes Through the Placental MembranePco2 of the fetal blood is 2 to 3 mm Hg higher than that of the maternal blood. Extreme solubility of carbon dioxide in the placental membrane CO2 diffuses about 20 times as rapidly as oxygen. Diffusion of Foodstuffs glucose, facilitated diffusion (carrier molecules in the trophoblast cells of the palcental membrane). fatty acids: simple diffusion (more slowly than glucose) ketone bodies and potassium, sodium, and chloride ions: Simple diffusion Excretion of Waste Products Non-protein nitrogens such as urea, uric acid, and creatinine. Depend on diffusion gradients across the placental membrane and its permeability.
16 Human Chorionic Gonadotropin - hCGSecreted by the syncytial trophoblast cells into the fluids of the mother, 8 to 9 days after ovulation (shortly after implantation) Rate of secretion rises rapidly to reach a maximum at about 10 to 12 weeks of pregnancy Secretion then decreases back to a lower value by 16 to 20 weeks & continues at this elevated level for the remainder of pregnancy.
17 Function of Human Chorionic GonadotropinCauses persistence of the corpus luteum and prevents menstruation Continued secretion of estrogens and progesterone by Corpus Luteum maintains the decidual nature of the uterine endometrium, which is necessary for the early development of the fetus. The corpus luteum involutes slowly after the 13th to 17th week of gestation. Exerts an interstitial cell-stimulating effect on the testes of the male fetus, resulting in the production of testosterone in male fetuses until the time of birth. Fetal testosterone causes the fetus to grow male sex organs instead of female organs. Fetal testosterone causes the testes to descend into the scrotum.
18 Secretion of Estrogens by the PlacentaThe placenta, like the corpus luteum, secretes both estrogens and progesterone. Estrogens are formed from androgenic compounds which are formed in the adrenal glands of the mother & the fetus & converted by the trophoblast cells into estradiol Functions of Estrogen in Pregnancy enlargement of the mother's uterus enlargement of the mother's breasts and growth of the breast ductal structure enlargement of the mother's female external genitalia. relaxation of the pelvic ligaments of the mother (sacroiliac joints & symphysis pubis) which allow easier passage of the fetus through the birth canal
19 Secretion of Progesterone by the PlacentaProgesterone is secreted in moderate quantities by the corpus luteum at the beginning of pregnancy, & later on in tremendous quantities by the placenta Functions of Progesterone in Pregnancy causes the decidual cells to develop in the uterine endometrium which play an important role in the nutrition of the early embryo decreases the contractility of the pregnant uterus, thus preventing abortion contributes to the development of the conceptus even before implantation, because it increases the secretion of the mother’s fallopian tubes & uterus to provide nutrients for the developing morula & blastocyst helps to prepare the mother’s breasts for lactation along with estrogen
20 Human Chorionic SomatomammotropinSecreted by the placenta at about the 5th week of pregnancy. Secretion increases progressively throughout pregnancy in direct proportion to the weight of the placenta. Secreted in quantities several times greater than all the other pregnancy hormones combined. possible important effects: causes decreased insulin sensitivity and decreased utilization of glucose in the mother, (making larger quantities of glucose available to the fetus). promotes the release and utilization of free fatty acids for energy in the mother Increases protein formation
21 Other Hormonal Factors in PregnancyAlmost all the non-sexual endocrine glands of the mother react with pregnancy. Due to increased metabolic load on the mother & the effects of the placental hormones on the endocrine glands. Pituitary Secretion AP enlarges & increases its production of corticotropin, thyrotropin, and prolactin. secretion of FSH and LH is suppressed (feedback inhibition of placental estrogen and progesterone). Increased Corticosteroid Secretion Increased secretion glucocorticoids (help mobilize amino acids from the mother's tissues to be used for synthesis of tissues in the fetus) Increased secretion of aldosterone (reabsorbs excess sodium from her renal tubules leading to fluid retention that might cause pregnancy-induced hypertension)
22 Other Hormonal Factors in PregnancyIncreased Thyroid Gland Secretion Thyroid gland enlarges & increases its production of thyroxine Due to thyrotropic effect of placental hCG & secretion of placental human chorionic thyrotropin Increased Parathyroid Gland Secretion Enlarges & causes calcium absorption from the mother's bones, thereby maintaining normal calcium ion concentration in the mother's extracellular fluid even while the fetus removes calcium to ossify its own bones (more intensified during lactation) Secretion of "Relaxin" by the Ovaries and Placenta secreted by the corpus luteum of the ovary and by placenta. causes relaxation of the ligaments of the symphysis pubis softens the cervix of the pregnant woman at the time of delivery.
23 Response of the Mother's Body to PregnancyWeight Gain in the Pregnant Woman About 25 to 35 pounds Weight of fetus, amniotic fluid, placenta, fetal membranes, uterus, breasts, extra fluid in the blood and ECF, and fat accumulation. Increased desire for food during pregnancy. Metabolism During Pregnancy The basal metabolic rate of the pregnant woman increases about 15 percent during the latter half of pregnancy (sensations of overheated)
24 Changes in the Maternal Circulatory System During PregnancyBlood flow through the placenta, and maternal cardiac output increases during pregnancy Maternal blood volume increases during pregnancy Due to aldosterone and estrogens, and to increased fluid retention by the kidneys. Also, the bone marrow becomes increasingly active and produces extra red blood cells Systemic vascular resistance
25 Other maternal Changes During PregnancyMaternal respiration during pregnancy mother's minute ventilation to increase progesterone increases the respiratory center's sensitivity to carbon dioxide. growing uterus presses upward against the abdominal contents, which press upward against the diaphragm (total excursion of the diaphragm is decreased & respiratory rate is increased to maintain the extra ventilation) Maternal kidney function during pregnancy rate of urine formation by a pregnant woman is usually slightly increased because of increased fluid intake and increased load of excretory products. renal tubules' reabsorptive capacity for sodium, chloride, and water is increased renal blood flow and glomerular filtration rate increase due to renal vasodilation. (NO or relaxin effect ???)
26 Preeclampsia; Toxemia; Pregnancy-induced hypertension (PIH)Medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine ~ 5 percent of all pregnancies Pathophysiology: excess salt and water retention by the mother's kidneys weight gain and development of edema and hypertension in the mother impaired function of the vascular endothelium and arterial spasm renal blood flow and Glomerular filtration rate are decreased thickened glomerular tufts that contain a protein deposit in the basement membranes. Causes: hormonal basis is still lacking. autoimmunity or allergy in the mother caused by the presence of the fetus. insufficient blood supply to the placenta, resulting in the placenta's release of substances that cause widespread dysfunction of the maternal vascular endothelium.
27 Eclampsia An extreme degree of preeclampsia, characterized by vascular spasm throughout the body; clonic seizures in the mother, sometimes followed by coma; greatly decreased kidney output; malfunction of the liver; often extreme hypertension; and a generalized toxic condition of the body. It usually occurs shortly before birth of the baby. Rx: vasodilating drugs followed by immediate termination of pregnancy
28 Parturition Parturition means birth of the babyIncreased Uterine Excitability Near Term progressive hormonal changes that cause increased excitability of the uterine musculature progressive mechanical changes.
29 Hormonal Factors That Increase Uterine ContractilityIncreased ratio of estrogens to progesterone Progesterone inhibits while estrogen increases uterine contractility during pregnancy, Estrogen-to-progesterone ratio increases sufficiently toward the end of pregnancy Oxytocin causes contraction of the uterus The uterine muscle increases its oxytocin receptors during the latter few months of pregnancy. The rate of oxytocin secretion by the neurohypophysis is considerably increased at the time of labor. Prolonged labor in hypophysectomized animals Stretching of the uterine cervix can cause a hypothalamic neurogenic reflex Effect of fetal hormones on the uterus Oxytocin, cortisol, & prostaglandins
30 Mechanical Factors That Increase Uterine ContractilityStretch of the Uterine Musculature Stretching smooth muscle organs increases their contractility. Twins are born, on average, 19 days earlier than a single child Stretch or Irritation of the Cervix The obstetrician frequently induces labor by rupturing the membranes so that the head of the baby stretches the cervix more forcefully than usual. Stretching of nerves in the cervix initiates reflexes to the body of the uterus Myogenic transmission of signals from the cervix to the body of the uterus.
31 Onset of Labor-a Positive Feedback Mechanism for Its InitiationBraxton Hicks contractions: periodic episodes of weak and slow rhythmical contractions during most of the months of pregnancy, become progressively stronger toward the end of pregnancy labor contractions: the strong contractions that result in final parturition positive feedback theory of labor
32 Onset of Labor-a Positive Feedback Mechanism for Its InitiationTwo types of positive feedback increase uterine contractions during labor: Stretching the cervix causes the entire body of the uterus to contract & this contraction stretches the cervix more because of the downward descend of the baby’s head. Cervical stretching causes the pituitary gland to secrete oxytocin which increase the uterine contractions False labor: labor contractions fade away. When contractions fail to re-excite the uterus sufficiently, the positive feedback declines and the labor contractions fade away.
33 Abdominal Muscle Contractions During LaborPain signals originate both from the uterus and from the birth canal elicit neurogenic reflexes in the spinal cord to the abdominal muscles, causing intense contractions of these muscles. The abdominal contractions add greatly to the force that causes expulsion of the baby.
34 Mechanics of ParturitionEach uterine contraction tends to force the baby downward toward the cervix. Labor contractions begin at the top of the uterine fundus and spread downward over the body of the uterus. Intensity of contraction is great in the top and body of the uterus but weak in the lower segment of the uterus adjacent to the cervix. Contractions frequency: early labor, once every 30 minutes. Eventually, once every 1 to 3 minutes Contractions of labor occur intermittently, to avoid stopping blood flow through the placenta
35 Separation and Delivery of the PlacentaFor 10 to 45 minutes after birth of the baby, the uterus continues to contract to a smaller and smaller size This shears & separates the placenta from the walls of the uterus Placental separation opens the placental sinuses and causes bleeding, but limited to an average of 350 milliliters by the following mechanism: The smooth muscle fibers of the uterine musculature are arranged in figures of 8 around the blood vessels as the vessels pass through the uterine wall. So, contraction of the uterus after delivery of the baby constricts the vessels that had previously supplied blood to the placenta. Vasoconstrictor prostaglandin formed at the placental separation site
36 Labor Pains Cramping pain in early laborProbably caused mainly by hypoxia of the uterine muscle resulting from compression of the blood vessels in the uterus. Hypogastric nerves Later on, when the fetus is being expelled through the birth canal, pain becomes much more severe Caused by cervical stretching, perineal stretching, and stretching or tearing of structures in the vaginal canal itself. Somatic nerves
37 Involution of the Uterus After ParturitionDuring the first 4 to 5 weeks after parturition, the uterus involutes. Decreases in weight Suppression of pituitary gonadotropin and ovarian hormone secretion during the first few months of lactation, Placental site on the endometrial surface autolyzes, causing a vaginal discharge known as "lochia," (first bloody and then serous) The endometrial surface becomes re-epithelialized and ready for normal, non gravid sex life again.
39 Hormonal Regulation of LactationFour other hormones are important for growth of the ductal system: growth hormone, prolactin, the adrenal glucocorticoids, and insulin (role in protein metabolism) Progesterone is required for full development of the lobule-alveolar system Budding of alveoli and development of secretory characteristics in the cells of the alveoli. These changes are analogous to the secretory effects of progesterone on the endometrium of the uterus during the latter half of the female menstrual cycle.
40 Hormonal Regulation of LactationProlactin Promotes Lactation Secreted by the mother's anterior pituitary gland Blood prolactin concentration rises steadily from the 5th week of pregnancy until birth of the baby Estrogen and progesterone inhibit the actual secretion of milk Placenta secretes large quantities of human chorionic somatomammotropin, (has lactogenic properties) Colostrum: a form of milk produced by the mammary glands of mammals in late pregnancy and the first few days after parturition. It contains antibodies to protect the newborn against disease, as well as being lower in fat and higher in protein (growth factors, enzymes …) than ordinary milk. It has some laxative effect (passing the baby's first stool) Newborns have very immature digestive systems, and colostrum delivers its nutrients in a very concentrated low-volume form. It has a mild laxative effect, encouraging the passing of the baby's first stool, which is called meconium. This clears excess bilirubin, a waste-product of dead red blood cells, which is produced in large quantities at birth due to blood volume reduction, from the infant's body and helps prevent jaundice. Colostrum is known to contain antibodies called immunoglobulins such as IgA, IgG, and IgM in mammals. IgA is absorbed through the intestinal epithelium, travels through the blood, and is secreted onto other Type 1 mucosal surfaces. These are the major components of the adaptive immune system. Other immune components of colostrum include the major components of the innate immune system, such as lactoferrin,[4] lysozyme,[5] lactoperoxidase,[6] complement,[7] and proline-rich polypeptides (PRP).[8] A number of cytokines (small messenger peptides that control the functioning of the immune system) are found in colostrum as well,[9] including interleukins,[9] tumor necrosis factor,[10] chemokines,[11] and others. Colostrum also contains a number of growth factors, such as insulin-like growth factors I,[12] and II,[13] transforming growth factors alpha,[14] beta 1 and beta 2,[15][16] fibroblast growth factors,[17] epidermal growth factor,[18] granulocyte-macrophage-stimulating growth factor,[19] platelet-derived growth factor,[19] vascular endothelial growth factor,[20] and colony-stimulating factor-1.[21] Colostrum is very rich in proteins, vitamin A, and sodium chloride, but contains lower amounts of carbohydrates, lipids, and potassium than normal milk. The most pertinent bioactive components in colostrum are growth factors and antimicrobial factors. The antibodies in colostrum provide passive immunity, while growth factors stimulate the development of the gut. They are passed to the neonate and provide the first protection against pathogens.
41 Hormonal Regulation of LactationImmediately after birth, secretion of both estrogen and progesterone from the placenta decreases which allows the lactogenic effect of prolactin Each time the mother nurses her baby, nervous signals from the nipples to the hypothalamus cause an intermittent 10- to 20-fold surge in prolactin secretion that lasts for about 1 hour If this prolactin surge is absent or blocked as a result of hypothalamic or pituitary damage or if nursing does not continue, 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, although the rate of milk formation normally decreases considerably after 7 to 9 months.
42 Alveolar epithelial cellProlactin & Oxytocin Hypothalamus Myoepithelial cell Pituitary Target of Oxytocin Prolactin & Oxytocin Target of Prolactin Alveolar epithelial cell Suckling on one breast causes milk flow not only in that breast but also in the opposite breast. It is especially interesting that fondling of the baby by the mother or hearing the baby crying often gives enough of an emotional signal to the hypothalamus to cause milk ejection. Oxytocin is concerned with releasing or ejection of milk, while prolactin is concerned with synthesis & production of milk.
43 Ovarian Cycles in Nursing MothersIn most nursing mothers, the ovarian cycle (and ovulation) does not resume until a few weeks after cessation of nursing. Reason: the same nervous signals from the breasts to the hypothalamus that cause prolactin secretion inhibit secretion of GnRH by the hypothalamus. Thus suppressing formation of the LH & FSH. However, after several months of lactation, in some mothers, especially in those who nurse their babies only some of the time, the pituitary begins to secrete sufficient gonadotropic hormones to reinstate the monthly sexual cycle, even though nursing continues.
44 Inhibition of Milk EjectionPsychogenic factors or even generalized sympathetic nervous system stimulation throughout the mother's body can inhibit oxytocin secretion and consequently depress milk ejection. Many mothers must have an undisturbed period of adjustment after childbirth if they are to be successful in nursing their babies.
45 Composition of Milk Fat soluble vitamin A, D E & KMature milk contains on average: Energy; (750 kcal / liter) . Lipids (38 g / liter) - The main lipids found in human breast milk are the triacyl-glycerols, phospholipids, and fatty acids including essential fatty acids. Maternal diet does not affect the amount of fat in milk but does affect the types of fat. Cholesterol is present in breast milk . Casein (2.5 g / liter) - protein - Casein or curds are proteins with low solubility which complex with calcium. These are present in breast milk in much lower concentration than in cow's milk. Whey (0.64 g / liter) - protein (WP)- the whey proteins are located in the clear liquid left behind when clotted milk stands. The largest components are alpha-lactalbumen, lactoferrin, lyzozyme, albumen and immunoglobulins. Nonprotein Nitrogen (NPN) is used in amino acid synthesis and includes the nitrogen in urea, creatine, creatinine, uric acid and ammonia. Peptides, such as epidermal growth factor, somatomedin - C and insulin are also present in this fraction. Nucleotides such as cytidine monophosphate are derived from nucleic acids and play an important role in the immune system and protein synthesis. Lactose (70 g / liter) carbohydrate - Lactose is the major carbohydrate in breast milk. It is composed of galactose and glucose. Lactose concentration in breast milk increases over the duration of breastfeeding. It has a white appearance due to the presence of the emulsified lipids , partly to the presence of the calcium salt of casein. The pH of milk is Volume ; At the height of lactation, the human breasts can produce up to 1.5 liters of milk (about 50 fluid ounces). The immunologic components include ; Immunoglobulins ; Human milk contains all of the different antibodies (M, A, D, G, E), but secretory immunoglobulin A (sIgA) is the most abundant . lactoferrin,; which binds to iron, thus making it unavailable to pathogenic bacteria; lysozyme , which enhances sIgA bactericidal activity against gram-negative organisms; Mucins adhere to bacteria and viruses and help eliminate them from the body. Leukocytes; with the transition from colostrum to mature milk, the percentage of macrophages increases from 40-60% of the cells to 80-90% . Human milk contains various enzymes ; - Some are specific for the biosynthesis of milk in the mammary gland (eg, lactose synthetase, fatty acid synthetase, thioesterase), Others are specific for the digestion of proteins, fats, and carbohydrates that facilitate the infant's ability to break down food and to absorb human milk (such as lipase, and protease, amylase) Certain enzymes also serve as transport moieties for other substances, such as zinc, selenium, and magnesium. Some have antimicrobial activity such as lysozyme Fat soluble vitamin A, D E & K Water soluble vitamins in general are present ,their content reflective of the mother’s diet . Low vitamine B12 is seen in women who are vegetarians, malnourished or have had gastric bypass . Minerals ; The most important salts are calcium, sodium, potassium and magnesium, calcium representing the predominating mineral.
46 Human’s milk vs. Cow’s milkHuman milk has a higher content of water and lactose , but a lower content of protein compared to cows milk, Certain vitamins and minerals that are necessary for human development may be lacking in cow’s milk. Cow’s milk lacks some of the key immunological components that are required by the human infant and the foreign proteins may trigger allergic reactions in some babies. in babies and breast milk can be replaced or supplemented by Cow’s milk should be avoided appropriate milk supplements developed for infants.