Early intra-uterine nutrition Persistence of CL and continued secretion of progesterone causes excessive deposition of nutrients and swelling in the endometrial stromal cells Decidual cells Trophoblasts digest and imbibe these nutrients in the decidua

Early intra-uterine nutrition This is the only way of nutrition in 1st week after implantation Placenta starts supplying nutrition on about 16th day of fertilization Trophoblastic nutrition continues for 8th week of pregnancy

Placenta Trophoblastic cord grow and branch deep into the endometrium Fetal blood vessels grow into these cord Blood begins to flow on about 16th day of fertilization The final branches of the trophoblastic cords form placental villi Maternal blood sinuses surround these villi

Placenta

Placental membrane Consists of Total surface area- a few square meters Endothelium of the fetal capillaries Mesencymal tissue Layer of Cytotrophoblasts (early stages of placental development) Layer of Syncytial trophoblasts Total surface area- a few square meters Thickness- 3.5 micrometer Diffusion across the placental membrane Nutrients and other requirements to the fetus Waste products from the fetus into the mother

Placental permeability & conductance Net quantity of substance diffusing through the placental membrane /unit SA for a given concentration gradient across the placental membrane Total conductance Permeability X Total SA Early pregnancy Permeability very low Less surface area Thick placental membrane Later pregnancy Tremendous permeability and total conductance

Placental conductance

Diffusion of O2 Mean pO2 in maternal blood = 50 mm Hg Mean pO2 in fetal oxygenated blood= 30 mm Hg Mean pressure gradient across the placental membrane = 20 mm Hg O2 diffusing capacity= 1.2 ml/min Fetal oxygenated blood pO2 of only 30 mm Hg sufficient to supply required O2 to fetus because HbF has more O2 carrying capacity Hb concentration is 50% more than adult Double Bohr effect across the placental membrane Oxygen carrying capacity is inversely proportional to Pco2

HbF carries more O2

Diffusion of CO2 CO2 continuously formed in the fetus Fetal lungs nonfunctional CO2 must be excreted through maternal lungs Estrogen and progesterone affect maternal breathing to eliminate more CO2 pCO2 in maternal blood = 40 mm Hg pCO2 in fetal blood is always 2-3 mm Hg higher than maternal blood 20 times more rapid diffusion than O2

Crossing of other substances Food stuffs Diffusion – FA, Ketone bodies, Na, K, Cl Facilitated diffusion – glucose Active transport – AA, Ca, PO4, ascorbic acid Waste products of fetus other than CO2 Diffusion - Urea, Uric acid, creatinine

Hormonal factors Pregnancy

Hormones of placenta Five important hormones Human chorionic gonadotrophic hormone (HCGH) Estrogen Progesterone Human chorionic somatomammotrophic hormone Relaxin

Human chorionic gonadotrophic hormone (HCGH) Involution of Corpus Luteum occurs on 12th day after ovulation Menstruation occurs after 14th day of ovulation This has to be prevented if fertilized ovum has implanted HCG is the earliest placental hormone Secreted by Syncytial trophoblasts 8-9 day after ovulation

Human chorionic gonadotrophic hormone (HCGH) A glycoprotein MW = 39000 Functions similar to LH Most important Prevention of involution of CL and menstruation Continued production of estrogen and progesterone from CL for a few months Estrogen and progesterone cause continued growth of endometrium Formation of Decidual cells for early nutrition of the fetus

Human chorionic gonadotrophic hormone (HCGH) Removal of CL before 7th week of pregnancy → Spontaneous abortion Removal after 12th week → no abortion Placental Estrogen and progesterone are sufficient to maintain pregnancy CL of pregnancy slowly involutes between 13th to 17th week of gestation

Hormones in pregnancy

(HCGH) and fetal testes HCG similar to LH (ICSH) Stimulates fetal testicular interstitial cell of Leydig Production of testosterone Intrauterine functions of testosterone Development of male genitalia Descent of testes

Placental estrogen Secreted by Syncytial trophoblasts Level 30 times the non-gravid level Not synthesized de novo from acetate or cholesterol in the placenta Androgens from Adrenal cortex of mother and fetus are converted into estrogens Dehydroepiandrosterone 16-hydoxydehydoepiandrosterone Estriol is the most abundant amongst the placental estrogens

Functions of placental estrogen Estriol has weaker estrogenic potency than ovarian β-estradiol Functions of estrogens Enlargement of uterus Proliferation of endometrium Enlargement of breasts Laying down of ductile system of mammary gland Enlargement of external genitalia

Functions of placental estrogen Deposition of fats through out the adipose tissue Salt and water conservation by the kidneys Relaxation of pelvic ligaments Sacroiliac joint Pubic symphysis for easy passage of fetus during labor through birth canal

Placental progesterone Level about 10 times the non-gravid level Synthesis from adrenal androgens Functions Development of Decidual cells Increased secretion of FT and endometrial glands Reduced contractility of the uterus Development of alveoli and lobules of the mammary gland Final preparation the breasts for lactation

Human chorionic somatomammotrophic hormone Protein in nature MW = 38000 Secretion starts in 5th week Increases through out the pregnancy Causes development of breast for lactation (actual milk secretion in some lower animals) Initially named as placental lactogen Growth hormone like action (much weaker than GH) ↓ insulin sensitivity of maternal tissues → ↓ utilization of glucose by the mother Mobilization of FA for mother and fetus both

Hormonal Secretion by the Placenta

Other endocrine glands in pregnancy Pituitary ↑ ACTH, TSH, Prolactin ↓ FSH, LH Adrenal cortex ↑Cortisol, Aldosterone, androgens Thyroid gland ↑ T3, T4 Parathyroid gland ↑ parathyroid hormone Ovaries ↑ estrogen and progesterone form CL Secretion of relaxin Polypeptide of 9000 MW Also produced by placenta Causes relaxation of the pelvic ligaments

Response of the mother’s body to Pregnancy ↑ size of the reproductive organs Uterus increases from 50 gm to 1100 gm Breast double in size Enlargement of vagina and wider opening of the introitus Different changes in general appearance may occur Edema – salt and water retention Acne – excessive androgenic hormones Masculine features – excessive androgenic activity Acromegalic features – ↑GH, HCSMH

Response of the mother’s body to Pregnancy Weight gain Average 24 lbs Fetus 7 lbs Amniotic fluid, placenta & fetal membranes 4 lbs Uterus 2 lbs Breasts 2 lbs Salt & water and general increase 9 lbs ↑ appetite – if not controlled weight gain may be 75 lbs Metabolism ↑Hormone → ↑ metabolism 15 % increase in BMR More energy expenditure

Digestive System and nutrition Most of the wt. gain and nutritional needs are in later part of the pregnancy Less absorption from GIT in 3rd trimester Early part of pregnancy – storage of nutrients in placenta and maternal tissues Requirements increased Carbohydrates, proteins, fats, minerals, vitamins Iron 375 mg for fetal blood 600 mg for maternal blood Calcium Vitamin D Different deficiency syndromes may develop if requirements are not fulfilled

Cardiovascular System ↑Blood volume – 30% above normal ↑ COP up to 27th (30-40%) week, returns to almost normal in last 8 weeks ↑ heart rate and blood pressure Cardiovascular changes to meet needs of fetus

Increase in maternal blood volume

Respiratory System ↑ metabolism → ↑ O2 consumption ↑ CO2 production CO2 and progesterone increase the minute ventilation -50 % ↓PCO2 compared to non- pregnant level Diaphragm is raised movement is restricted rate is increased

Urinary System Responsible for excretion of more metabolites due to ↑ metabolism ↑ glomerular filtration rate ↑ urine formation ↑ reabsorption of salt and water Accumulation of extra 6 lbs of salt and water

Amniotic fluid Volume = 500 -1000 ml May be a few ml – several litters Water turn over time = 3 hours Electrolyte turn over time = 15 hours Formed from Secretion from amniotic vessels Renal excretion of the fetus Absorption into Amniotic blood vessels Fetal GIT

Toxemia of pregnancy Pre-eclampsia Causes Hypertension Albuminurea Edema Weight gain Vascular spasm in many parts of the body →↓ blood flow ↓ renal blood flow →↓ GFR Causes Unknown Autoimmunity to pregnancy Allergy to pregnancy Associated with insufficient blood flow to placenta Cytokines – tumor necrosis factor-α, interluekin-6

Toxemia of pregnancy Eclampsia Treatment Usually occurs shortly before labor Exaggeration of all the symptoms of pre-eclampsia Extreme vascular spasm Convulsions Coma Renal failure Hepatic failure Mortality rate very high Treatment Rapidly acting vasodilators Sedation Termination of the pregnancy

Thank-you Questions ??