Physiology & Psychology

1. Physiology & Psychology • Maternal physiological adaptations to pregnancy • The placenta • Psychosocial adaptations

2. Physiology of Pregnancy Goals: 1) Healthy mother 2) Appropriately grown, healthy fetus with low risk for adult disease

3. Systematic Adjustments to Pregnancy • Cardiovascular • Respiratory • Renal • GI

4. Cardiovascular Adaptations • Heart rate increases • 10-20% • Begins as early as 5 weeks • Peaks by 32 weeks • Stoke volume increases • 25-30% • Peeks at 16-24 weeks • Systemic Vascular Resistance decreases • 20% • As early as 5 weeks • Result of vascular smooth muscle relaxation • Allows changes in cardiac output without increase in arterial pressure

5. Cardiac Output Increases • Driven by increased maternal O2 consumption maternal heart and respiratory muscle demands • ½ of total increase occurs by 8 weeks • peaks at 30-50% above non-pregnant at 28-32 due to: • Changes in both stoke volume (early pregnancy) • Heart rate (late pregnancy) • Fall in systemic vascular resistance in T3

6. Cardiac output during three stages of gestation, labor, and immediately postpartum compared with values of nonpregnant women. All values were determined with women in the lateral recumbent position.

7. Respiratory Adaptations • 30% increased production of CO2 • 50% increase volume air and gas exchange • Increase in lung volume • Decreased airway resistance

9. Renal Function Changes • Renal blood flow • Increases 50-80% by end of 1st trimester • Decreases gradually to term • Glomerular filtration rate • Increases 40-50% • Begins at 5 weeks, peaks at 9-16 weeks • May decrease 15-20% from 36 weeks to term

10. Mean glomerular filtration rate in healthy women over a short period with infused inulin (solid line), simultaneously as creatinine clearance during the inulin infusion (broken line), and over 24 hours as endogenous creatinine clearance (dotted line).

11. GI Adaptations • Anatomic – growing uterus • Hormonal • Progesterone – relaxation of GI smooth muscle • Estrogen – increased tissue vascularity

12. Adjustments in Nutrient Metabolism • Goals • support changes in anatomy and physiology of mother • support fetal growth and development • maintain maternal homeostasis • prepare for lactation • Adjustments are complex and evolve throughout pregnancy

13. General Concepts 1. Alterations include: • increased intestinal absorption • reduced excretion by kidney or GI tract 2. Alterations are driven by: • hormonal changes • fetal demands • maternal nutrient supply

14. 3. There may be more than one adjustment for each nutrient. 4. Maternal behavioral changes augment physiologic adjustments 5. When adjustment limits are exceeded, fetal growth and development are impaired.

15. Birth weight of 11 children born to a poor woman in Montreal; 8 children were born before receiving nutritional counseling and food supplements from the Montreal Diet Dispensary and 3 children were born afterward.

16. 6. The first half of pregnancy is a time of preparation for the demands of rapid fetal growth in the second half

17. 7. Alterations in maternal physiology facilitate transfer of nutrients to the fetus.

18. Nitrogen Balance (g/day)

19. Hormonal Adjustments • Changes in over 30 different hormones have been detected in pregnancy • Estrogens: increase significantly in pregnancy, influence carbohydrate, lipid, and bone metabolism • Progesterone: relaxes smooth muscle and causes atony of GI and urinary tract • Human Placental Lactogen (hPL): stimulates maternal metabolism, increases insulin resistance, aids glucose transport across placenta, stimulates breast development

20. Late gestation is characterized by: • Anti-insulinogenic and lipolytic effects of Human chorionic somatomammotropin, prolactin, cortisol, glucagon) Which Results in: • Glucose intolerance, insulin resistance, decreased hepatic glycogen, mobilization of adipose tissue

22. Maternal Nutrient Levels • Increased triglycerides • Increased cholesterol • Decreased plasma amino acids & albumin

24. Lipids

25. Maternal Albumin

26. Maternal Plasma volume increases ~ 40% • range 30-50% • nutrient concentration declines due to increased volume, but total amount of vitamins and minerals in circulation actually increases.

28. Mean hemoglobin concentrations (  —  ) and 5th and 95th (  —  ) percentiles for healthy pregnant women taking iron supplements

29. Embryonic and Placental Development • http://www.youtube.com/watch?v=UgT5rUQ9EmQ • http://www.youtube.com/watch?v=jo3NjApFSQE • http://www.youtube.com/watch?v=YJL9roi1LbM&feature=related

33. Embryonic Development • In early gestation Embryo is nourished by secretions of the oviduct and uterine endometrial glands • Uterine secretions include growth factors (e.g. TNFa, epidermal growth factor) that promote placental growth • Growth trajectories of both placenta and fetus are established early & have lifelong consequences

34. Nutrient Availability & Maternal Metabolic Status • Blastocyst development & implantation are reduced • diabetic mothers • animal models with insufficient nutrients • Poorly nourished women and obese women at risk for aberrations in embryonic and placental development • Congenital anomalies • Adverse outcomes later in pregnancy (e.g. preeclampsia)

35. The Placenta • 10-12 weeks is the period of placentation • Rapid early growth prepares way for fetal growth • Trophoblast cells use same molecular mechanisms as tumors, but are highly regulated and controlled

36. Placental Functions • Maintains immunological distance between mother and fetus • Special endocrine organ: “transient hypothalamo-pituitary-gonadal axis” • Responsible for exchange of nutrients, gases & metabolic waste products between maternal and fetal circulation

37. Placental Architecture • Maternal and fetal blood do not mix: “placental barrier” • Fetal blood flows through capillary networks within highly branched terminal chorionic villi • Maternal blood flows through intervillous space • Uterine arteriols bring blood in • Uterine venules drain blood

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39. Placental Capacity Increases During Gestation • Expression of transporters increases • The “brush border” microvilli develop to: • increase surface area • impede maternal blood flow • Flow through the placenta at term is 500 ml/minute

41. Mechanisms of Nutrient Transfer Across the Placenta

42. Maternal to Infant Nutrient Transportation Across The Placenta

43. Fetal to Maternal Transport • Carbon dioxide • Water & urea • Signaling Molecules: Hormones, cytokines, others

45. Factors Affecting Placental Transfer • Placental size • Diffusion distance – • diabetes and infection cause edema of the villi • distance decreases as pregnancy progresses and fetal needs increase • Maternal-placental blood flow • Blood saturation with gases and nutrients

46. Factors Affecting Placental Transfer (cont) • Maternal-placental metabolism of the substance • Disorders in expression or activity of nutrient transporters • Maternal use of tobacco, cocaine, alcohol

47. Metabolic Functions of the Placenta • Glycogen synthesis: from maternal glucose & stored • Cholesterol synthesis: placental cholesterol is precursor for placental progesterone and estrogens • Protein production: rises to 7.5 g per day at term • Lactate: produced in large quantities and needs to be removed

48. Endocrine Functions • Placenta Produces Peptide hormones • Human Chorionic gonodotrophin (hCG) - secreted early and helps to maintain synthesis of progesterone • Human placental lactogen (hPL): increase supply of glucose to future by decreasing maternal stores of fatty acids by altering maternal secretion of insulin • Insulin-like growth factors (IGF): IGF signaling system is a major regulator of growth in fetus and infant

49. Endocrine Functions • Steroid hormones • Progesterone: produced by placenta, needed to maintain non-contractile uterus • Estrogen: produced by placenta drives many processes in pregnancy • Glucocorticoids: placenta regulates fetal exposure

50. Emerging Understandings • Cytokines & Inflammatory molecules are produced by the placenta as well as adipocytes • Adverse outcomes in obese women may be associated with imbalances due to overproduction from both sources • “In pregnancy complicated with obesity or DM, continuous adverse stimulus is associated with dysregulation of metabolic, vasular and inflammatory pathways.”