1. Physiology of Pregnancy Daniel Hodyc Department of Physiology

2. Pregnancy 1. Fertilization 2. Placenta development, nutrition 3. Hormonal changes during pregnancy 4. Other physiological changes 5. Metabolism

3. Fertilization

4. Fertilization in the ampulle of the FT. Prostaglandins Oxytocin Ectopic (extrauterine) gravidity

5. Fertilization Transport into the uterus - 3-5 days Contraction of the FT isthmus Relaxation - progesteron

6. Fertilization Implantation 5-7 days after fertilization Proteolytic enzymes of the trophoblast cells

7. Placenta

8. Placenta development Early nutrition of the embryo - invasion of trophoblastic cells into the decidua Progesteron produced by CL - stimulates decidual cells to concentrate glycogen, proteins and lipids

9. Placenta works as a physiological A-V shunt

10. Placenta - oxygen transport Similarities betwen placenta and lungs Oxygen transport - simple difusion Lungs pO 2 in alveoli…………………………..100mmHg pO 2 in the venous blood……………40mmHg dO 2 in (pressure gradient)…………60mmHg Placenta: pO 2 in placental sinuses…………50mmHg pO 2 in fetal umbilical vein………30mmHg dO 2 in (pressure gradient)………20mmHg How is a sufficient oxygenation of the fetus possible?

11. Placenta - oxygen transport 1. Fetal hemoglobin 2. Higher Hb concentration in the fetal blood (50% more than in adults) 3. Double Bohr effect - Hb can carry more oxygen in low pCO 2 than in high pCO 2

12. Placenta - CO 2, nutritients, waste products transport CO 2 gradient - 2-3 mmHg, but extreme solubility (diffuses 20times faster than oxygen) facilitated diffusion for glucose (high glucose need in 3dr trimester) free diffusion of fatty acids diffusion of waste products based on concentration gradient drugs crossing placental barier - teratogens: Talidomide, Carbamazepine, Coumarins, Tetracycline… Alcohol, nicotine, heroin, cocaine, caffeine drugs (excluding alcohol) - 3% of all congenital malformations

13. Hormonal Changes During Pregnancy

14. Hormonal changes HCG HCS Human Chorionic Gonadotropin prevent involution of CL (pregesterone, estrogen) effect on the testes of male fetus - development of sex organs Human Chorionic Somatomammotropin effect on latation (HPL) ? growth hormone effects decreases insulin sensitivity - more glucose for the fetus low levels - placental insuf.

15. Hormonal changes Progesterone Estrogens development of decidual cells decreases uterus contractility preparation for the lactation enlargement of uterus breasts development relaxation of ligments estriol level - indicator of vitality of the fetus

16. Progesterone and Cortisol metabolism Placenta

17. Hormonal changes PlacentaMother CRHACTH aldosterone cortisol edema insulin resistance HCG HC thyrotropin hyperthyroidism hypertension gestational diabetes HyperparathyroidismCalcium demands

18. Other Physiological Changes

19. Cardiovascular changes Cardiac output (CO) 30 -50% above normal placental circulation increased metabolism skin - thermoregulation renal circulation decreases in last 8 weeks (uterus compresses vena cava) incr. 30% more during labor Heart rate (HR) increases up to 90/min Blood pressure (BP) drops, periferal resistance decreases with twins CO increases more, BP drops more ECG changes functional murmurs heart sounds

20. Hematologic changes plasma volume increases (50%) erythropoesis (RBC) increases (25%) decreased Hb, hematocrite Iron requirements increases significantly Iron suplements needed

21. Respiratory changes oxygen consumption increases 20% above normal Progesterone increases sensitivity for CO 2 in respiratory centre Growing uterus Frequency increases Minute ventilation increases (50%) pCO 2 decreases slightly

22. Urinary system Glomerulat filtration rate and renal plasma flow increases (up to 30 - 50 %) Increased reabsorption of ions and water - placental steroids - aldosterone Slight increase of urine formation Postural changes affect renal functions - upright position - supine position - lateral position during sleep

23. Preeclampsia, Eclampsia Preeclampsia - pregnancy induced hypertension + proteinuria Incresing BP since 20th week - hypertension Salt and water retention - edema formation RBF and GFR decreases extensive secretion of placental hormones ? insufficient blood supply to placenta - ischemia - increased resistance - TNF alfa, cytokines ? Eclampsia - vascular spasms, chronic seizures, coma

24. Nutrition and Metabolism

25. Maternal weight gain Fetus 5 kg Mother 6 kg

26. Maternal-Fetal Metabolism 250 - 300 extra kcal/day should be ingested - 85% fetal metabolism, 15% stored in maternal fat Extra protein intake - 30g/day End of pregnancy - fetal glucose need 5mg/kg/min (mother 2,5mg/kg/min) 2 phases of pregnancy: 1st - 20th week - mother´s anabolic phase: - anabolic metabolism of the mother - quite small nutrition demands of the conceptus 21 - 40 week (esp. last trimester): - high metabolic demands of the fetus - accelerated starvation of the mother

27. Maternal-Fetal Metabolism Mother´s anabolic phase: - normal or increased sensitivity to insulin - lower plasmatic glucose level - lipogeneses, glycogen stores increases - growth of breasts, uterus,weight gain Catabolic phase (accelerated starvation): - maternal insuln resistance - increased transport of nutritients trough placental membrane - lipolysis Insulin resistance caused by HCS, cortisol and growth hormone

28. Special nutrition need in pregnancy High protein diet, higher energy uptake Iron supplements - 300mg ferrous sulfate B - vitamins - erythropoesis Folic acid (folate) - reduces risk of neural tube defects Vitamin D3 + Ca supplements Before parturition - K vitamin (prevention of intracranial bleeding during the labor)

29. Thank you for attention