Maternal physiology Sindhu Srinivas, md, msce division of Maternal Fetal Medicine Goals



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Maternal physiology

  • Sindhu Srinivas, MD, MSCE
  • Division of Maternal Fetal Medicine

Goals

  • To understand the normal changes associated with pregnancy

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

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)

Hematology – RBC mass

  • Red blood cell mass increases by 250-450 cc by term
  • Increased production
  • Possibly hormonally mediated

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

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?

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

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

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

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)

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

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

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

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

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

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

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

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%

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

QUESTION

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

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

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

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.

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

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

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

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

QUESTION

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

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

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

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

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

Renal system

  • NUTRIENT EXCRETION
    • Increase in glucose excretion
      • 1-10 g glucose excretion per day
        • Due to 50% increase in GFR
      • implications
    • Increase in amino acid excretion during gestation
      • no increased protein loss (100-300 mg/24 hr)
    • Increased urinary loss of folate and vitamin B12

QUESTION

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

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

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

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

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

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

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

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

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

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

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

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

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

Endocrine - Pancreas

  • Fetus primarily depends on glucose
    • Facilitated diffusion
      • carrier-mediated but not energy dependent process
  • Active transport of amino acids to the fetus
  • Ketones diffuse freely across the placenta

Endocrine - Pituitary

  • The pituitary gland enlarges in pregnancy
    • proliferation of chromophobe cells on the anterior pituitary
    • stalk remains midline

Skin

  • Spider angiomata (face, upper chest, and arm) and palmar erythema
    • elevated estrogen levels
    • both regress after delivery
  • Striae gravidarum
  • Increased eccrine sweating and sebum excretion

Skin

  • Hyperpigmentation
  • Melasma: “mask of pregnancy”
    • elevated e2 and p4
  • Nevi may darken, enlarge or show increased activity
    • rapidly changing nevi should be excised
  • Hairs in telogen phase decrease in late pregnancy
    • increases after delivery
    • hair loss 2-4 mos pp
    • re-growth in 6-12 mos
  • Masculinization of the skin rarely occurs
    • evaluate for possible luteomas of pregnancy (which regress after delivery)

Breasts

  • Early change
    • tenderness, tingling and heaviness
    • vascular engorgement leads to enlargement
      • Ductal growth due to e2
      • Alveolar hypertrophy due to p4
  • Enlargement and pigmentation of areolae
  • Colostrum may be expressed later in pregnancy
  • Milk production
    • E2, p4, prolactin, hPL, cortisol and insulin
    • Lactation likely due to drop in estrogen and progesterone after delivery

Skeleton

  • Lordosis
    • keep center of gravity over the legs
    • back pain…
  • Relaxin
    • relaxation of the pubic symphysis and sacroiliac joints
      • facilitates vaginal delivery but may lead to discomfort
  • Implications
    • unsteadiness of gait and trauma from falls

Skeleton

  • Total serum calcium declines throughout pregnancy until 34-36 weeks
    • due to the fall in serum albumin
  • Serum ionized calcium is constant and unchanged
    • “Physiologic hyperparathyroidism”
      • increased gut absorption
      • decreased renal losses
      • no bone loss seen in bone density studies
        • preservation due to calcitonin?
  • Rate of bone turnover and remodeling increases throughout pregnancy
    • twice as great at term

Eye

  • Increased thickness of cornea due to fluid retention (contact lens intolerance)
  • Decreased intraocular pressure

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