Maternal Adaptations To Pregnancy: I
Maternal physiology must adapt in response to a series of demands attendant to pregnancy (Fig. 20.1). The pregnant woman needs to increase her circulating blood volume to supply nutrients to the fetus and to support amniotic fluid production. She must clear fetal waste products and protect her pregnancy from systemic perturbations, including starvation or medication ingestion. She must meet fetal and placental nutritional demands for glucose, amino acids and oxygen. The maternal system must adapt to allow for timely onset of labor and for protection of the mother from cardiovascular insults at the time of delivery. It must also prepare to support nourishment of the infant after delivery. All maternal organ systems are affected to some degree.
During the first two trimesters of pregnancy, maternal circulating blood volume increases 40% (3500 cm3 expands to 5000 cm3) with the largest expansion occurring during the second trimester (Fig. 20.2). The functions of pregnancy-induced hypervolumia are to meet the demands of the enlarged uterus with its greatly hypertrophied vascular system, to provide nutrients to the growing placenta and fetus, to protect both mother and fetus from impaired venous return in certain postures, and to ensure that the mother does not suffer any adverse effects from the obligatory blood loss at delivery.
The increase in plasma volume results from a combination of a modest (10 mOsm/kg) decrease in plasma osmolality and from water retention through enhanced activity of the renin–angiotensin system. Placental estrogen increases hepatic production of angiotensinogen, and estrogen and progesterone together increase renal production of the proteolytic enzyme, renin. Renin cleaves angiotensinogen to form angiotensin I, which converts into angiotensin II (AII) in the lung and elsewhere. The increased amounts of AII act on the zona glomerulosa of the adrenal gland to increase aldosterone production. Aldosterone promotes volume expansion through sodium and water retention. Oxygen-carrying capacity must be maintained in the presence of this increase in circulating blood volume. Iron absorption increases to meet the demand for increased hemoglobin during volume expansion.
A loss of peripheral vascular responsiveness to AII accompanies the increase in circulating blood volume. AII is a potent vasoconstrictor and loss of AII responsivity results in a drop in maternal blood pressure during the early second trimester. This relative hypotension is seen in most pregnant women despite elevated AII levels. Maternal blood pressure slowly rises to prepregnancy levels by the third trimester. Progesterone promotes overall smooth muscle relaxation and is thereby partially responsible for alterations in maternal blood pressure. Production of prostacyclin, the principal endothelial prostaglandin, also increases during pregnancy and has been implicated in the development of angiotensin resistance.
Immediately following delivery of the fetus and placenta, a venous “autotransfusion” from the extremities, pelvis and empty uterus into the right heart occurs. Women with a normal cardiovascular system tolerate this event well but it is a major challenge for women with mitral valve stenosis and Eisenmenger syndrome in whom the increased venous return can result in pulmonary edema and hypoxia.
An increase in tidal volume, minute ventilatory volume and minute O2 uptake develops in pregnant women. These changes allow for increased oxygen delivery to the fetus and the periphery. They also cause a mild maternal respiratory alkalosis that is compensated for by increased renal bicarbonate excretion. Progesterone may be responsible for many of these changes. The decrease in plasma bicarbonate shifts the O2 dissociation curve to the left and increases the affinity of maternal hemoglobin for oxygen (the Bohr effect). This decreases the O2 releasing capacity of the maternal blood which is offset by an increase in 2,3-diphosphoglycerate induced by the increase in pH. This shifts O2 dissociation curve back to the right. Fetal hemoglobin binds O2 at a lower partial pressure than maternal adult hemoglobin. The net result of these changes is to favor transfer of O2 from mother to fetus within the placenta and to facilitate CO2 (waste) transfer back from the fetus to the mother.
Many pregnant women have the sensation of shortness of breath in the absence of pathology. This physiologic dyspnea may be the result of decreased pCO2. It is important to note that the blood gas pH of a pregnant woman should be in the alkalotic range with a decrease in pCO2 and bicarbonate and, if not, requires further investigation.
Kidney and urinary tract
Maternal glomerular filtration rate (GFR) and renal plasma flow (RPF) begin to increase in early pregnancy. By midpregnancy, maternal GFR has increased by as much as 50%; it remains elevated throughout gestation. In contrast, maternal RPF begins to decrease in the third trimester. As a result, the renal filtration fraction increases during the last third of pregnancy. Because of the increased GFR, serum creatinine and urea are lower in pregnancy than in the nonpregnant state. Creatinine clearance is increased.
A 60–70% increase in the filtered load of sodium also accompanies the increased GFR. Progesterone appears to cause some sodium wastage by interfering with normal sodium resorption in the proximal renal tubule. In response, aldosterone increases proportionately to levels that are 2–3 times normal. Renal medullary prostaglandin E2 synthesis also increases in late pregnancy, enhancing sodium natriuresis.
The relatively fixed renal tubular reabsorptive capacity, in combination with an increased GFR, causes a decrease in the reabsorption of glucose from the proximal tubule of the pregnant woman’s kidney. Glucose is therefore detectable in the urine of about 15% of healthy pregnant women. Still, any pregnant woman exhibiting glycosuria should be evaluated for diabetes.
The volume of urine contained in the renal pelves and ureters can double in the latter half of pregnancy. The renal collecting system dilates during pregnancy as a result of mechanical obstruction by the pregnant uterus combined with the relaxing effects of progesterone upon smooth muscle. This dilatation decreases the speed of urine passage through the renal system and increases the maternal risk of developing acute kidney infections.
Pregnant women are mildly anemic. Maternal hemoglobin production and total red blood cell mass increase during pregnancy in response to elevated erythropoietin production. Maternal vascular volume increases to a greater extent. The result is a mild maternal dilutional anemia that protects the mother from excess hemoglobin loss at delivery. The iron requirements of normal pregnancy must satisfy both maternal and fetal red cell production requirements and total about 1.0 g. Most is needed during the second half of pregnancy. Amounts of iron absorbed from diet alone, as well as any mobilized from maternal stores, may be insufficient to meet the demand.
Pregnant women develop a modest leukocytosis that can become quite marked during labor and postpartum. The etiology of the mild leukocytosis of early pregnancy is unclear. That seen during labor, however, resembles the leukocytosis associated with strenuous exercise, during which previously sequestered white cells re-enter the active circulation.
Pregnant women are hypercoagulable. Increased coagulability develops because of the increased procoagulant synthesis in the liver (Chapter 21). Up to 8% of women will develop a mild thrombocytopenia (<150 000 platelets/ml). This typically does not result in a bleeding diathesis. The mechanism by which the thrombocytopenia develops is unknown.
Circulating melanotrophic hormone (MSH) is increased during pregnancy as a result of the increased production of the precursor molecule proopiomelanocortin (POM-C) (Chapter 18). MSH causes darkening on the skin across the cheeks (chloasma or pregnancy mask) and darkening of the linea alba, the slightly pigmented line on the skin that runs from the navel to the pubis. Hair may also appear to fall out in clumps because of synchronization of hair follicle growth cycles during pregnancy.