Maternal physiology

1. Maternal physiology Sindhu Srinivas, MD, MSCE Division of Maternal Fetal Medicine

2. Goals To understand the normal changes associated with pregnancy

3. Body Water • TBW increases from 6.5L to 8.5L • At term water content of fetus, placenta and AF is 3.5L • BV, PV, RBC, extravascular, intracellular • Pregnancy is a condition of chronic volume overload • Water retention exceeds Na retention-decreased plasma osmolality (Na dec by 3-4) To recognize physiologic and pathologic states during pregnancy

4. Hematology – Blood volume • Increases progressively from 6 to 8 weeks’ gestation • maximum volume at 32 weeks - 45% increase • possibly due to estrogen stimulation of renin-angiotensin-aldosterone system (Inc Prog, NO->Dec SVR->Dec MAP->Inc Na retention)

5. Hematology – RBC mass • Red blood cell mass increases by 250-450 cc by term • Increased production • Possibly hormonally mediated

6. Hematology - Iron • Maternal requirement is 1000mg • normal pregnant woman needs to absorb about 3.5 mg/day of iron • the goal of iron supplementation is to prevent maternal iron deficiency • iron is actively transported to the fetus

7. Hematologic changes • IMPLICATIONS • The increase in plasma volume and rbc mass translates into a 45% increase in circulating blood volume • may protect from hemodynamic instability • may serve to dissipate fetal heat production and provide increase renal filtration • physiologic anemia of pregnancy • may function to decrease blood viscosity • may improve intervillous perfusion?

8. Hematology • LEUKOCYTES • Peripheral wbc rises progressively during pregnancy • 1st ∆ – mean 9500/mm3 (3000-15,000) • 2nd and 3rd ∆ – mean 10,500 (6000-16,000) • Labor – may rise to 20-30,000 • Rise is due to increase in pmns (demargination) • PLATELETS • Platelets experience a progressive decline but should remain within normal range • Likely due to increased destruction

9. Hematology • COAGULATION FACTORS • Increased levels • Fibrinogen (Factor I) • Factors VII through X • No change in prothrombin (Factor II), Factors V and XII • Decline in platelet count, Factors XI and XIII • Bleeding time and clotting time are unchanged in normal pregnancy

10. Cardiovascular – Cardiac output • Maternal cardiac output increases about 30-50% during pregnancy (mean 33%) • pregnancy maximum of 6 L/min • CO remains maximal until delivery • Earliest rise in CO is due to increase in SV • As pregnancy progresses • Gradual increase in mat HR (15-20 bpm rise) • SV declines to near non-pregnant levels • increase HR is what maintains the elevated CO

12. Cardiovascular – Cardiac output • CO is position dependent • Lower when supine • IVC compression by the uterus reduces venous return to the heart • At 38-40 weeks, there is a 25-30% fall in CO when turning from the side to the back • Fall in CO is compensated by a rise in peripheral vascular resistance • supine hypotensive syndrome (1-10% patients)

13. Cardiovascular – Cardiac output • Distribution of CO • First trimester and non-pregnant state • Uterus receives 2-3% • By term • Uterus receives 17% • Breasts 2% • Reduction of the fraction of CO going to the splanchnic bed and skeletal muscle • CO to the kidneys, skin, brain and coronary arteries does not change

14. Cardiovascular – Arterial BP • BP varies with position • Peripheral vascular resistance falls during pregnancy • Progesterone’s smooth muscle relaxing effect • ?heat production by the fetus  vasodilatation • The reduction in PVR may lead to a progressive fall in systemic arterial bp during the first 24 weeks of pregnancy • Gradual rise after 24 weeks non-pregnant levels by term

15. Cardiovascular – Venous system • Venous compliance increases during pregnancy • decrease in flow velocity and stasis • ?progesterone effects on smooth muscle • Forearm venous pressure increases by 40-50% • Calf venous pressures are always higher • due to the enlarging uterus

16. Cardiovascular - LV function • Left ventricular dimensions and volume increase during pregnancy • most parameters of LVF are the same as in the non-pregnant state • Ejection fraction, rate of internal diameter shortening, percentage of fractional shortening, and ventricular wall thickness • Bottom line: preservation of myocardial function

17. Signs and Symptoms of Normal Pregnancy • Symptoms • reduced exercise tolerance • dyspnea • Signs • peripheral edema • distended neck veins • point of maximal impulse displaced to the left

18. Signs and Symptoms of Normal Pregnancy • Auscultation • increased splitting of the first and second heart sound • S3 gallop • SEM along the left sternal border • Continuous murmurs

19. Signs and Symptoms of Normal Pregnancy • CXR • straightening of left heart border • heart position more horizontal – may appear as cardiomegaly on cxr • increased vascular markings in lungs • ECG • left axis deviation • non-specific ST-T wave changes

20. Cardiovascular - Labor • First stage of labor: 12-31% rise on CO due to an increase in SV • Second stage of labor: 34% increase in CO • Not only pain-related • UCs result in the transfer of 300-500 cc of blood from the uterus to the general circulation • Enhanced venous return to the heart • Increase in CO by 10-15%

21. Cardiovascular - Postpartum • Immediate pp period: 10-20% rise in CO • release of obstruction of venous return • extracellular fluid mobilization • Rise in CO associated with reflex bradycardia • SV increases  this may persist for one to two weeks after delivery

22. QUESTION • During which of the following states is the blood pressure lowest? • First trimester • Second trimester • Third trimester • Non pregnant

23. QUESTION • Increased cardiac output immediately postpartum is due to: • Increased HR • Release of obstruction of venous return • Reduced mobilization of extracellular fluid • Reduced stroke volume

24. Respiratory system • UPPER RESPIRATORY TRACT • Hyperemic mucosa of nasopharynx • Estrogen-mediated • nasal stuffiness and epistaxis • Polyposis of nose and sinuses may occur and regress after delivery • “chronic cold” • MECHANICAL CHANGES • Configuration of thoracic cage changes early in pregnancy • Increase in subcostal angle, transverse diameter and circumference of chest • With advancing gestation, the level of diaphragm is pushed up

26. Changes in pulmonary function tests during pregnancy Serial measurements of lung volume compartments during pregnancy. Functional residual capacity decreases approximately 20 percent during the latter half of pregnancy, due to a decrease in both expiratory reserve volume and residual volume. Redrawn from Prowse, CM, Gaensler, EA, Anesthesiology 1965; 26:381. Serial measurements of lung volume compartments during pregnancy. Functional residual capacity decreases approximately 20 percent during the latter half of pregnancy, due to a decrease in both expiratory reserve volume and residual volume. Redrawn from Prowse, CM, Gaensler, EA, Anesthesiology 1965; 26:381.

27. Respiratory system • LUNG VOLUME AND PULMONARY FUNCTION • 30-40% increase in tidal volume (Amount of air I and E with each breath) • 30-40% increase in minute ventilation (likely P4 mediated) • ERV falls by 20% • Vital capacity and inspiratory reserve volume remain unchanged

28. Respiratory system • LUNG VOLUME AND PULMONARY FUNCTION • Respiratory rate is unchanged • Due to elevation of the diaphragm • Total lung volume decreases (diaphragm) by 5% • Residual volume decreases (RV) by 20% • FRC is reduced 20% • No change in FEV1 or the ratio of FEV1 to forced vital capacity

29. Respiratory system • GAS EXCHANGE • Minute ventilation rises 30-40% by late pregnancy • O2 consumption increases only 15-29% • Results in higher PAO2 (alveolar) and PaO2 (arterial) • Normal PaO2: 104-108 mmHg • Fall in PACO2 and PaCO2 levels • Normal PaCO2 level: 27-32 mmHg • Increases gradient of CO2 facilitating transfer from fetus to mother • Arterial pH remains unchanged • Increased bicarbonate excretion via kidneys

30. Respiratory system • DYSPNEA OF PREGNANCY • Common complaint • 60-70% of patients • late first or early second trimester • Likely due to various factors • reduced PaCO2 levels • awareness of increased tidal volume of pregnancy

31. QUESTION • Which of the following is increased in pregnancy? • FRC • ERV • RV • TV

32. Renal system • ANATOMY • Kidney enlargement • increased renal vascular and interstitial volume, R>L • Ureteral and renal pelvis dilatation by 8 weeks • Right > left • mechanical compression by uterus and ovarian venous plexus • smooth muscle relaxation by progesterone • Implications • Increased incidence of pyelonephritis • difficulty in interpreting radiographs • interference with studies

33. Renal system • RENAL HEMODYNAMICS • Effective renal plasma flow (ERPF) and GFR increase • Filtration fraction falls • Returns to normal by late third Δ • Endogenous creatinine clearance increases • Begins by 5 weeks

34. Renal system • METABOLITES • increased GFR decline in serum urea and creatinine • BUN – 8-9 mg/dl by end 1st Δ • Decline in serum creatinine • 0.7 mg/dl by end 1st Δ • 0.5-0.6 mg/dl by term • Early decline in serum uric acid levels • nadir at 24 weeks • same as nonpregnant level at end of pregnancy due to increased reabsorption of urate

35. Renal system • SALT AND WATER METABOLISM • Plasma osmolality begins to decline by 2 weeks after conception • reduction in serum sodium and other anions • Sodium loss during pregnancy • 50% rise in GFR • Progesterone: natriuresis • Renal tubular reabsorption of Na+ increases (aldosterone, estrogen and deoxycorticosterone) • Sodium homeostasis

36. Renal system • NUTRIENT EXCRETION • Increase in glucose excretion • 1-10 g glucose excretion per day • Due to 50% increase in GFR • implications • inability to use urine glucose • susceptibility of pregnant women to UTI • Increase in amino acid excretion during gestation • no increased protein loss (100-300 mg/24 hr) • Increased urinary loss of folate and vitamin B12

37. QUESTION • All of the following are increased in pregnancy except: • Renal plasma flow • GFR • Serum creatinine • Tubular sodium resorption

38. Gastrointestinal - Appetite • Increase early 1st Δ • Increase intake 200 kcal by end 1st Δ • RDA: 300 kcal/day during pregnancy • Sense of taste may be blunted • Pica • check for poor weight gain and refractory anemia • South - clay or starch (laundry or cornstarch) • UK – coal • Also soap, toothpaste and ice pica

39. Gastrointestinal - Mouth • Unchanged pH or production of saliva • Saliva production is unaltered • Ptyalism – usually in women with HEG • due to inability to swallow • Can lose up to 1-2 L of saliva per day • Decreasing starchy foods might help • Gums – edematous and soft • May bleed after brushing • Epulis gravidarum • regress 1-2 mos after delivery • excise if persistent or excessive bleeding

40. Gastrointestinal - Stomach • Decreased tone and motility • progesterone • possibly due to decreased levels of motility • Conflicting info about delayed gastric emptying • Reduced tone of the gastroesophageal junction sphincter • Increased intraabdominal pressure leads to acid reflux • Lower incidence of PUD • may be due to decreased gastric acid secretion delayed emptying, increase in gastric mucus, and protection of mucosa by prostaglandins

41. Gastrointestinal - Small bowel • Reduced motility of small bowel • increased transit time in the third trimester and postpartum • Enhanced iron absorption • as a response to increased iron needs

42. Gastrointestinal - Colon • Constipation • Mechanical obstruction by the uterus • Reduced motility (p4) • Increased water absorption • Portal venous pressure is increased • Dilation of gastroesophageal vessels • issue in those with preexisting esophageal varices • Dilation of hemorrhoidal veins • hemorrhoids

43. Gastrointestinal - Gallbladder • Fasting and residual volumes double in 2nd and 3rd Δ • Slower rate of emptying • Biliary cholesterol saturation increases and chenodeoxycholic acid decreases • increased risk gallstone formation

44. Gastrointestinal - Liver • Liver does not enlarge • Hepatic blood flow remains unchanged • CO to the liver decreases by ~35% • Spider angiomata and palmar erythema • elevated estrogen levels • Lab data • Drop in serum albumin • Rise in serum alkaline phosphatase • placental production and some hepatic production • Rise in serum cholesterol, fibrinogen, ceruloplasmin, binding proteins for corticosteroids, sex steroids, thyroid hormones, and vitamin D • No change in serum bilirubin, AST, ALT, protime and 5’ nucleotidase • Rise in GGT is controversial

45. Gastrointestinal system • NAUSEA AND VOMITING • Morning sickness complicates 70% of pregnancies • Onset 4-8 weeks up to 14-16 weeks • Cause? • Relaxation of smooth muscle of stomach, elevated levels of steroids and hCG • Rx – supportive: reassurance, support, and avoiding triggers… • HEG • weight loss, ketonemia, electrolyte imbalance and dehydration • possible renal or hepatic damage • IVF, antiemetics • NPO • continue IV

47. Conclusion • Understanding maternal physiology is crucial in understanding the changes and clinical scenarios associated in pregnancy • This knowledge will help us distinguish the physiologic and pathologic processes during pregnancy • This knowledge will also improve patient’s education about their pregnancy

48. Endocrine - Thyroid • The normal pregnant woman is euthyroid • Changes in thyroid morphology and lab indices • Estrogen-induced increase in TBG • Decreased circulating extrathyroidal iodide • Thyroid enlargement usually not detected by exam • Normal thyroidal uptake of iodide • Serum TSH decreases early in gestation • rises to pre-pregnancy levels by end of first Δ • T4 increases early in gestation • role of hCG stimulating the thyroid • Rise in TBG leads to rise in total T4 and total T3 • active hormones free T4 and free T3 are unchanged • Free T4 is the most reliable method of evaluating thyroid function in pregnancy

49. Endocrine - Adrenal glands • Expansion of the zona fasciculata • site of glucocorticoid production • Plasma corticosteroid-binding globulin (CBG) rises • due to enhanced liver synthesis • Free plasma cortisol rises • increased production and delayed clearance • Plasma DOC (deoxycorticosterone) rises • fetoplacental unit • DHEAS (dehydroepiandrosterone) decreases • Testosterone is slightly elevated • Increased SHBG and androstenedione

50. Endocrine - Pancreas • Hypertrophy and hyperplasia of the B cells • Fasting associated with accelerated starvation • maternal hypoglycemia, hypoinsulinemia and hyperketonemia • due to diffusion of glucose by the fetoplacental unit • Feeding response • hyperglycemia, hyperinsulinemia, hypertriglyceridemia and reduced tissue sensitivity to insulin • glucose response greater during pregnancy • peripheral resistance to insulin: diabetogenic effect of pregnancy. • hPL and cortisol mediated • greater insulin resistance as the pregnancy advances