Medical Physiology, 3rd Edition

Response of the Mother to Pregnancy

The mean duration of human pregnancy is ~266 days (38 weeks) from the time of ovulation or 280 days (40 weeks) from the first day of the last menstrual period. During this time, the mother experiences numerous and profound adaptive changes in her cardiovascular system, fluid volume, respiration, fuel metabolism, and nutrition. These orderly changes reflect the effects of various hormones as well as the increase in the size of the pregnant uterus.

Both maternal cardiac output and blood volume increase during pregnancy

The maternal blood volume starts to increase during the first trimester, expands rapidly during the second trimester, rises at a much lower rate during the third trimester, and finally achieves a plateau during the last several weeks of pregnancy. Maternal blood volume may have increased by as much as 45% near term in singleton pregnancies and up to 75% to 100% in twin or triplet pregnancies. The increase in blood volume is due to an increase in the volume of both the plasma and erythrocytes. However, the rise in plasma volume begins earlier and is ultimately greater (~50%) than the rise in total erythrocyte volume (~33%). A proposed mechanism for the increase in plasma volume is that elevated progesterone and estrogens cause a vasodilation that decreases peripheral vascular resistance and thus renal perfusion. One mechanism of the vasodilation is refractoriness to the pressor effects of angiotensin II. The renin-angiotensin-aldosterone axis responds by increasing aldosterone (see pp. 841–842), which augments renal reabsorption of salt and water. In addition, pregnancy causes a leftward shift of the relationship between arginine vasopressin (AVP) release and plasma osmolality (see Fig. 40-7). Immediately after the delivery of the placenta, with the attendant decreases in progesterone and estrogen levels, the mother commences a vigorous diuresis.

The increase in blood volume is needed to meet the demands of the enlarged pregnant uterus with its greatly hypertrophied vascular system. It also protects mother and fetus against the deleterious effects of impaired venous return in the supine and erect positions, and it safeguards the mother against the adverse effects of the blood loss associated with parturition.

Cardiac output increases appreciably during the first trimester of pregnancy (by 35% to 40%), but increases only slightly during the second and third trimesters (~45% at term). The increase in cardiac output, which reflects mainly an increase in stroke volume but also in heart rate, is highly targeted. Renal blood flow increases 40%. Uterine blood flow rises from just 1% to 15% of cardiac output. Blood flow to the heart (to support increased cardiac output), skin (to increase heat radiation), and breasts (to support mammary development) also increases. However, no change occurs in blood flow to the brain, gut, or skeleton. The increase in cardiac output with physical activity is greater in pregnant women (for most of the pregnancy) than it is in nonpregnant women.

Despite the large increase in plasma volume, mean arterial pressure (MAP) usually decreases during midpregnancy and then rises during the third trimester, although it normally remains at or lower than normal. The reason for this initial fall in MAP is a decrease in peripheral vascular resistance, possibly reflecting—in part—the aforementioned vasodilating effects of progesterone and estradiol.

Posture has a major effect on cardiac output (see pp. 575–576). In late pregnancy, cardiac output is typically higher when the mother is in the lateral recumbent position than when she is in the supine position. In the supine position, the fundus of the enlarged uterus rests on the inferior vena cava near L5, thereby impeding venous return to the heart.

Increased levels of progesterone during pregnancy increase alveolar ventilation

During pregnancy, hormonal and mechanical factors lead to several anatomical changes that have the net effect of increasing alveolar ventilation. The level of the diaphragm rises ~4 cm, which probably reflects the relaxing effects of progesterone on the diaphragm muscle and fascia. At the same time, the costovertebral angle widens appreciably as the transverse diameter of the thoracic cage increases ~2 cm. Although these two changes have opposite effects on the residual volume (RV) of air in the lungs (see p. 602), the elevation of the diaphragm dominates, which causes a net decrease in RV and functional residual capacity (FRC). Vital capacity (VC), maximal pulmonary ventilation, and pulmonary compliance do not change appreciably. Total pulmonary resistance falls, which facilitates airflow. Because of the increased size of the abdominal contents during pregnancy, the abdominal muscles are less effective in aiding forced expirations.

Although pregnancy has little effect on respiratory rate, it increases tidal volume (VT) markedly—by ~40%—and thereby increases alveolar ventilation (image; see pp. 675–676). These increases in VT and image are some of the earliest physiological changes during pregnancy, beginning 6 weeks after fertilization. They may reflect, at least in part, a direct stimulatory effect of progesterone and, to a lesser extent, estrogen on the medullary respiratory centers. The physiological effect of the increased image during pregnancy is a fall in maternal arterial image, which typically decreases from ~40 mm Hg before pregnancy to ~32 mm Hg, despite the net increase in CO2 production that reflects fetal metabolism. A side effect is mild respiratory alkalosis for which the kidneys compensate by lowering plasma [image] modestly (see p. 641).

Pregnancy increases the demand for dietary protein, iron, and folic acid

During pregnancy, an additional 30 g of protein will be needed each day to meet the demand of the growing fetus, placenta, uterus, and breasts, as well as the increased maternal blood volume. Most protein should come from animal sources, such as meat, milk, eggs, cheese, poultry, and fish, because these foods furnish amino acids in optimal combinations.

Almost any diet that includes iodized salt and adequate caloric intake to support the pregnancy also contains enough minerals, except iron (see Table 45-4). Pregnancy necessitates a net gain of ~800 mg of circulating iron to support the expanding maternal Hb mass, the placenta, and the fetus. Most of this iron is used during the latter half of pregnancy. A nonpregnant woman of reproductive age needs to absorb ~1.5 mg/day of iron in a diet that contains 15 to 20 mg/day (see p. 939). In contrast, during pregnancy, the average required iron uptake rises to ~7 mg/day. Very few women have adequate iron stores to supply this amount of iron, and a typical diet seldom contains sufficient iron. Thus, the recommended supplementation of elemental iron is 60 mg/day, taken in the form of a simple ferrous iron salt.

Maternal folate requirements increase significantly during pregnancy, in part reflecting an increased demand for producing blood cells. This increased demand can lead to lowered plasma folate levels or, in extreme cases, to maternal megaloblastic anemia (see pp. 933–935). Folate deficiency may cause neural tube defects in the developing fetus. Because oral supplementation of 400 to 800 µg/day of folic acid produces a vigorous hematological response in pregnant women with severe megaloblastic anemia, this dosage would almost certainly provide very effective prophylaxis.

Less than one third of the total maternal weight gain during pregnancy represents the fetus

The recommended weight gain during a singleton pregnancy for a woman with a normal ratio of weight to height (i.e., body mass index) is 11.5 to 16 kg. This number is higher for women with a low body mass index. A weight gain of 14 kg would include 5 kg for intrauterine contents—the fetus (3.3 kg), placenta and membranes (0.7 kg), and amniotic fluid (1 kg). The maternal contribution of 9 kg would include increases in the weight of the uterus (0.7 kg), imageN56-8 the blood (1.3 kg), and the breasts (2.0 kg), as well as adipose tissue and interstitial fluid (5.0 kg). The interstitial fluid expansion may be partly the result of increased venous pressure created by the large pregnant uterus and, as noted above, partly caused by aldosterone-dependent Na+ retention (see p. 1142).


Uterine Growth during Pregnancy

Contributed by Sam Mesiano

During the first weeks of pregnancy, most of uterine growth is due to hyperplasia, whereas during the latter part of pregnancy, the growth is due mainly to stretch-induced hypertrophy.


Ramsey EM. Anatomy of the human uterus. Chard T, Grudzinskas JG. The Uterus. Cambridge University Press: Cambridge, UK; 1994:18–40.

Rehman KD, Yin S, Mayhew BA, et al. Human myometrial adaptation to pregnancy: cDNA microarray gene expression profiling of myometrium from non-pregnant and pregnant women. Mol Hum Reprod. 2003;9:681–700.

For a woman whose weight is normal before pregnancy, a weight gain in the recommended range correlates well with a favorable outcome of the pregnancy. Most pregnant women can achieve an adequate weight gain by eating—according to appetite—a diet adequate in calories, protein, minerals, and vitamins. Seldom, if ever, should maternal weight gain be deliberately restricted to less than this level. Failure to gain weight is an ominous sign; birth weight parallels maternal weight, and neonatal mortality rises with low birth weight, particularly for babies weighing <2500 g.





Upper motor neuron



Significantly impaired

Lower motor neuron



Less impaired