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Physiology of Pregnancy
The earliest sign of pregnancy and the reason most pregnant women initially see a physician is missing a menstrual period. For sexually active women who are of reproductive age and have regular periods, a period that is ≥ 1 wk late is presumptive evidence of pregnancy.
Pregnancy is considered to last 266 days from the time of conception or 280 days from the first day of the last menstrual period if periods occur regularly every 28 days. Delivery date is estimated based on the last menstrual period. Delivery up to 2 wk earlier or later than the estimated date is normal.
Pregnancy causes physiologic changes in all maternal organ systems; most return to normal after delivery. In general, the changes are more dramatic in multifetal than in single pregnancies.
Cardiac output (CO) increases 30 to 50%, beginning by 6 wk gestation and peaking between 16 and 28 wk (usually at about 24 wk). It remains near peak levels until after 30 wk. Then, CO becomes sensitive to body position. Positions that cause the enlarging uterus to obstruct the vena cava the most (eg, the recumbent position) cause CO to decrease the most. On average, CO usually decreases slightly from 30 wk until labor begins. During labor, CO increases another 30%. After delivery, the uterus contracts, and CO drops rapidly to about 15 to 25% above normal, then gradually decreases (mostly over the next 3 to 4 wk) until it reaches the prepregnancy level at about 6 wk postpartum.
The increase in CO during pregnancy is due mainly to demands of the uteroplacental circulation; volume of the uteroplacental circulation increases markedly, and circulation within the intervillous space acts partly as an arteriovenous shunt. As the placenta and fetus develop, blood flow to the uterus must increase to about 1 L/min (20% of normal CO) at term. Increased needs of the skin (to regulate temperature) and kidneys (to excrete fetal wastes) account for some of the increased CO.
To increase CO, heart rate increases from the normal 70 to as high as 90 beats/min, and stroke volume increases. During the 2nd trimester, BP usually drops (and pulse pressure widens), even though CO and renin and angiotensin levels increase, because uteroplacental circulation expands (the placental intervillous space develops) and systemic vascular resistance decreases. Resistance decreases because blood viscosity and sensitivity to angiotensin decrease. During the 3rd trimester, BP may return to normal. With twins, CO increases more and diastolic BP is lower at 20 wk than with a single fetus.
Exercise increases CO, heart rate, O2 consumption, and respiratory volume/min more during pregnancy than at other times. The hyperdynamic circulation of pregnancy increases frequency of functional murmurs and accentuates heart sounds. X-ray or ECG may show the heart displaced into a horizontal position, rotating to the left, with increased transverse diameter. Premature atrial and ventricular beats are common during pregnancy. All these changes are normal and should not be erroneously diagnosed as a heart disorder; they can usually be managed with reassurance alone. However, paroxysms of atrial tachycardia occur more frequently in pregnant women and may require prophylactic digitalization or other antiarrhythmic drugs. Pregnancy does not affect the indications for or safety of cardioversion.
Total blood volume increases proportionally with CO, but the increase in plasma volume is greater (close to 50%, usually by about 1600 mL for a total of 5200 mL) than that in RBC mass (about 25%); thus, Hb is lowered by dilution, from about 13.3 to 12.1 g/dL. This dilutional anemia decreases blood viscosity. With twins, total maternal blood volume increases more (closer to 60%).
WBC count increases slightly to 9,000 to 12,000/μL. Marked leukocytosis (≥ 20,000/μL) occurs during labor and the first few days postpartum.
Iron requirements increase by a total of about 1 g during the entire pregnancy and are higher during the 2nd half of pregnancy—6 to 7 mg/day. The fetus and placenta use about 300 mg of iron, and the increased maternal RBC mass requires an additional 500 mg. Excretion accounts for 200 mg. Iron supplements are needed to prevent a further decrease in Hb levels because the amount absorbed from the diet and recruited from iron stores (average total of 300 to 500 mg) is usually insufficient to meet the demands of pregnancy.
Changes in renal function roughly parallel those in cardiac function. GFR increases 30 to 50%, peaks between 16 and 24 wk gestation, and remains at that level until nearly term, when it may decrease slightly because uterine pressure on the vena cava often causes venous stasis in the lower extremities. Renal plasma flow increases in proportion to GFR. As a result, BUN decreases, usually to < 10 mg/dL (< 3.6 mmol urea/L), and creatinine levels decrease proportionally to 0.5 to 0.7 mg/dL (44 to 62 μmol/L). Marked dilation of the ureters (hydroureter) is caused by hormonal influences (predominantly progesterone) and by backup due to pressure from the enlarged uterus on the ureters, which can also cause hydronephrosis. Postpartum, the urinary collecting system may take as long as 12 wk to return to normal.
Postural changes affect renal function more during pregnancy than at other times; ie, the supine position increases renal function more, and upright positions decrease renal function more. Renal function also markedly increases in the lateral position, particularly when lying on the left side; this position relieves the pressure that the enlarged uterus puts on the great vessels when pregnant women are supine. This positional increase in renal function is one reason pregnant women need to urinate frequently when trying to sleep.
Lung function changes partly because progesterone increases and partly because the enlarging uterus interferes with lung expansion. Progesterone signals the brain to lower CO2 levels. To lower CO2 levels, tidal and minute volume and respiratory rate increase, thus increasing plasma pH. O2 consumption increases by about 20% to meet the increased metabolic needs of the fetus, placenta, and several maternal organs. Inspiratory and expiratory reserve, residual volume and capacity, and plasma Pco2 decrease. Vital capacity and plasma Po2 do not change. Thoracic circumference increases by about 10 cm. Considerable hyperemia and edema of the respiratory tract occur. Occasionally, symptomatic nasopharyngeal obstruction and nasal stuffiness occur, eustachian tubes are transiently blocked, and tone and quality of voice change. Mild dyspnea during exertion is common, and deep respirations are more frequent.
As pregnancy progresses, pressure from the enlarging uterus on the rectum and lower portion of the colon may cause constipation. GI motility decreases because elevated progesterone levels relax smooth muscle. Heartburn and belching are common, possibly resulting from delayed gastric emptying and gastroesophageal reflux due to relaxation of the lower esophageal sphincter and diaphragmatic hiatus. HCl production decreases; thus, peptic ulcer disease is uncommon during pregnancy, and preexisting ulcers often become less severe.
Incidence of gallbladder disorders increases somewhat. Pregnancy subtly affects hepatic function, especially bile transport. Routine liver function test values are normal, except for alkaline phosphatase levels, which increase progressively during the 3rd trimester and may be 2 to 3 times normal at term; the increase is due to placental production of this enzyme rather than hepatic dysfunction.
Pregnancy alters the function of most endocrine glands, partly because the placenta produces hormones and partly because most hormones circulate in protein-bound forms and protein binding increases during pregnancy.
The placenta produces a hormone (similar to thyroid-stimulating hormone) that stimulates the thyroid, causing hyperplasia, increased vascularity, and moderate enlargement. Estrogen stimulates hepatocytes, causing increased thyroid-binding globulin levels; thus, although total thyroxine levels may increase, levels of free thyroid hormones remain normal. Effects of thyroid hormone tend to increase and may resemble hyperthyroidism, with tachycardia, palpitations, excessive perspiration, and emotional instability. However, true hyperthyroidism occurs in only 0.08% of pregnancies.
The placenta produces corticotropin-releasing hormone (CRH), which stimulates maternal ACTH production. Increased ACTH levels increase levels of adrenal hormones, especially aldosterone and cortisol, and thus contribute to edema. Increased production of corticosteroids and increased placental production of progesterone lead to insulin resistance and an increased need for insulin , as does the stress of pregnancy and possibly the increased level of human placental lactogen. Insulinase, produced by the placenta, may also increase insulin requirements, so that many women with gestational diabetes develop more overt forms of diabetes ( Diabetes Mellitus (DM) and Diabetes Mellitus in Pregnancy (Gestational Diabetes)).
The placenta produces melanocyte-stimulating hormone (MSH), which increases skin pigmentation late in pregnancy. The placenta also produces the β subunit of human chorionic gonadotropin (β-hCG), a trophic hormone that, like follicle-stimulating and luteinizing hormones, maintains the corpus luteum and thereby prevents ovulation.
The pituitary gland enlarges by about 135% during pregnancy. The maternal plasma prolactin level increases by 10-fold. Increased prolactin is related to an increase in thyrotropin -releasing hormone production, stimulated by estrogen . The primary function of increased prolactin is to ensure lactation. The level returns to normal postpartum, even in women who breastfeed.
Increased levels of estrogens , progesterone, and MSH contribute to pigmentary changes, although exact pathogenesis is unknown. These changes include melasma (mask of pregnancy), which is a blotchy, brownish pigment over the forehead and malar eminences; darkening of the mammary areolae, axilla, and genitals; and linea nigra, a dark line that appears down the midabdomen. Melasma due to pregnancy usually regresses within a year.
Incidence of spider angiomas, usually only above the waist, and of thin-walled, dilated capillaries, especially in the lower legs, increases.
Pregnancy may cause breasts to be engorged because of increased levels of estrogen (primarily) and progesterone—an extension of premenstrual breast engorgement. Nausea, occasionally with vomiting, may occur because of increased secretion of estrogen and the β subunit of human chorionic gonadotropin (β-hCG) by syncytial cells of the placenta, beginning 10 days after fertilization (see Conception and Prenatal Development). The corpus luteum in the ovary, stimulated by β-hCG, continues secreting large amounts of estrogen and progesterone to maintain the pregnancy. Many women become fatigued at this time, and a few women notice abdominal bloating very early. Women usually begin to feel fetal movement between 16 and 20 wk. During late pregnancy, lower-extremity edema and varicose veins are common; the main cause is compression of the inferior vena cava by the enlarged uterus.
Pelvic examination findings include a softer cervix and an irregularly softened, enlarged uterus. The cervix usually becomes bluish to purple, probably because blood supply to the uterus is increased. Around 12 wk gestation, the uterus extends above the true pelvis into the abdomen; at 20 wk, it reaches the umbilicus; and by 36 wk, the upper pole almost reaches the xiphoid process.
Usually urine and occasionally blood tests are used to confirm or exclude pregnancy; results are usually accurate several days before a missed menstrual period and often as early as several days after conception. Levels of β-hCG, which correlate with gestational age in normal pregnancies, can be used to determine whether a fetus is growing normally. The best approach is to compare 2 serum β-hCG values, obtained 48 to 72 h apart and measured by the same laboratory. In a normal single pregnancy, β-hCG levels double about every 1.4 to 2.1 days during the first 60 days (7.5 wk), then begin to decrease between 10 and 18 wk. Regular doubling of the β-hCG level during the 1st trimester strongly suggests normal growth.
Other accepted signs of pregnancy include the following:
Presence of a gestational sac in the uterus, seen with ultrasonography typically at about 4 to 5 wk and typically corresponding to a serum β-hCG level of about 1500 mIU/mL (a yolk sac can usually be seen in the gestational sac by 5 wk)
Fetal heart motion, seen with real-time ultrasonography as early as 5 to 6 wk
Fetal heart sounds, heard with Doppler ultrasonography as early as 8 to 10 wk if the uterus is accessible abdominally
Fetal movements felt by the examining physician after 20 wk
Drug NameSelect Trade
corticotropinH.P. ACTHAR GEL
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