Physiology of Pregnancy - Through the Life Cycle

Conception triggers thousands of complex and sequenced biological changes that transform two united cells into a member of the next generation of human beings.

The rapidity with which structures and functions develop in mother and fetus and the time-critical nature of energy and nutrient needs make maternal nutritional status a key element of successful reproduction.

Pregnancy begins at conception; that occurs approxi-mately 14 days before a woman’s next menstrual period is scheduled to begin. Assessed from conception, pregnancy averages 38 weeks, or 266 days, in length. Most com-monly, however, pregnancy duration is given as 40 weeks (280 days) because it is measured from the date of the first day of the last menstrual period (LMP). Consequently, the common way of measuring pregnancy duration includes two nonpregnant weeks at the beginning. The anticipated date of delivery is denoted by the ancient terminology of

“estimated date of confinement,” or EDC. Assessment of Table 4.3 Range of birth weights by gestational age, U.S.⁷

Birth Weight

Weeks Gestation

Infant Mortality Rate Pounds (lb) and Ounces (oz) Grams

,1 lb 2 oz ,500 ,22 846

1 lb 2 oz–2 lb 3 oz 500–999 22–27 316

2 lb 3 oz–3 lb 5 oz 1000–1499 27–29 62

3 lb 5 oz–4 lb 6 oz 1500–1999 29–31 28

4 lb 6 oz–5 lb 8 oz 2000–2499 31–33 12

5 lb 8 oz–6 lb 10 oz 2500–2999 33–36 4.6

6 lb 10 oz–7 lb 11 oz 3000–3499 36–40 2.4

7 lb 11 oz–8 lb 13 oz 3500–3999 401 1.7

8 lb 13 oz–9 lb 14 oz 4000–4499 401 1.5

9 lb 14 oz–11 lb 4500–4999 401 2.5

.11 lb 50001 401 —

Table 4.4 Rates of preterm delivery and low birth weight for the United States’ population and by ethnic/racial background, 2007²

Preterm

Low Birth Weight

All races and origins 12.7 8.2

Blacks 18.3 13.8

Whites 11.5 7.2

American Indian/

Alaskan Native 13.9 7.5

Asian/Pacific Islander 10.9 8.1

Hispanic 12.3 6.9

Table 4.5 Health objectives for the nation related to pregnant women and infants

Reduce anemia among low-income pregnant females

•

in their third trimester from 29 to 20%.

Reduce infant mortality from 7.6 to no more than

•

5 per 1000 live births.

Reduce the incidence of spina bifida and other neural

•

tube defects from 7 to 3 per 10,000 live births.

Reduce low birth weight (

• ,2500 g) from 7.3 to 5%.

Reduce preterm births (

• ,37 weeks) from 9.1 to 7.6%.

Increase abstinence from alcohol use by pregnant

•

women from 79 to 95%.

Reduce the incidence of fetal alcohol syndrome.

•

Increase the proportion of women who gain weight

•

appropriately during pregnancy.

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Similarly, the maximal rate of placental growth is timed to precede that of fetal weight gain. This sequence of events en-sures that the placenta is fully prepared for the high level of functioning that will be needed as fetal weight increases most rapidly. Fetuses depend on the function-ing of multiple systems, established well in advance of their maximal rates of growth and development. Abnormali-ties in the development of any of these physiological systems can modify sub-sequent fetal growth and development.

Normal Physiological Changes During Pregnancy

Physiological changes in pregnancy can be divided into two basic groups: those occurring in the first half of pregnancy and those in the second half. In general, physio logical changes in the first half are considered “maternal anabolic”

changes because they build the capacity of the mother’s body to deliver relatively large quantities of blood, oxygen, and nutrients to the fetus in the second half of pregnancy.

The second half is a time of “maternal catabolic” changes in which energy and nutrient stores, and the heightened capacity to deliver stored energy and nutrients to the fe-tus, predominate (Table 4.7). Approximately 10% of fetal growth is accomplished in the first half of pregnancy, and the remaining 90% occurs in the second half.¹²

The list of physiological changes that normally oc-cur during pregnancy is extensive (Table 4.8), and such changes affect every maternal organ and system. Changes that are most directly related to maternal energy and nutrient needs are discussed further.

Body Water Changes A woman’s body gains a good deal of water during pregnancy, primarily due to in-creased volumes of plasma and extracellular fluid, as well as amniotic fluid.¹⁴ Total body water increases in to bring blood nutrient levels back up to “normal.” We

now know that what is considered normal physiological status of nonpregnant women cannot be considered nor-mal for women who are pregnant. Fortunately, it is now understood that attempts to bring maternal physiological changes back to nonpregnant levels may cause more harm than good to the pregnancy.

Changes in maternal body composition and functions occur in a specific sequence during pregnancy. The order of the sequence is absolute because the successful completion of each change depends on the one before it. Because ma-ternal physiological changes set the stage for fetal growth and development, they begin in earnest within a week after conception.¹⁰

The sequence of physiological changes taking place during pregnancy is listed in Table 4.6. The table indi-cates the timing of maximal rates of change in maternal tissues, the placenta, and fetal weight across pregnancy.

To provide the fetus with sufficient energy, nutrients, and oxygen for growth, the mother must first expand the vol-ume of plasma that can be circulated. Maternal nutrient

stores are accumulated next.

These stores are established in advance of the time they will be needed to support large gains in fetal weight.

Placenta A disk-shaped organ of nutrient and gas interchange between mother and fetus. At term, the placenta weighs about 15% of the weight of the fetus.

Table 4.6 Sequence of tissue development and approximate gestational week of maximal rates of change in maternal systems, the placenta, and fetus during pregnancy¹⁰

Tissue

Sequence of Development

Gestational Week of Maximal Rate of Growth

Maternal plasma volume 1 20

Maternal nutrient stores 2 20

Placental weight 3 31

Uterine blood flow 4 37

Fetal weight 5 37

Table 4.7 Summary of maternal anabolic and catabolic phases of pregnancy^11–13

Maternal Anabolic Phase 0220 Weeks

Maternal Catabolic Phase 201 Weeks Blood volume expansion, increased cardiac output Mobilization of fat and nutrient stores

Buildup of fat, nutrient, and liver glycogen stores Increased production and blood levels of glucose, triglycerides, and fatty acids; decreased liver glycogen stores

Growth of some maternal organs Accelerated fasting metabolism

Increased appetite, food intake (positive caloric balance) Increased appetite and food intake decline somewhat near term

Decreased exercise tolerance Increased levels of catabolic hormones Increased levels of anabolic hormones

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increase in pregnancy, whereas levels of the water-soluble vitamins tend to decrease. Vitamin supplement use can modify these relationships.¹³

Hormonal Changes Many physiological changes in pregnancy are modulated by hormones produced by the pla-centa. Table 4.9 summarizes normal physiological changes that occur in pregnancy, and Illustration 4.3 presents a pic-ture of how hormone levels change. The placenta serves many roles, but a key one is the production of steroid hor-mones, such as progesterone and estrogen. The placenta is also the main supplier of many other hormones needed to support the physiological changes of pregnancy.

Maternal Nutrient Metabolism Adjustments in ma-ternal nutrient metabolism are apparent within the first few weeks after conception

and progress throughout pregnancy.¹² Many of the adjustments are directed toward ensuring that nutri-ents will be available to the fetus during periods of high nutrient need. Fetal nutrient pregnancy range from 7 to 10 liters (approximately 7 to

10 quarts, or about 2 to 2½ gallons). About two-thirds of the expansion is intracellular (blood and body tissues) and one-third is extracellular (fluid in spaces between cells).¹⁰ Plasma volume begins to increase within a few weeks af-ter conception and reaches a maximum at approximately 34 weeks. Early pregnancy surges in plasma volume ap-pear to be the primary reason that pregnant women feel tired and become exhausted easily when undertaking ex-ercise performed routinely prior to pregnancy. Fatigue as-sociated with plasma-volume increases in the second and third months of pregnancy declines as other compensa-tory physiological adjustments are made.

Gains in body water vary a good deal among women during normal pregnancy. High gains are associated with increasing degrees of edema and weight gain. If not accom-panied by hypertension, edema generally reflects a healthy expansion of plasma volume. Birth weight is strongly re-lated to plasma volume: generally, the greater the expan-sion, the greater the newborn size.¹⁰ The increased volume of water in the blood is responsible for the “dilution effect”

of pregnancy on blood concentrations of some vitamins and minerals. Blood levels of fat-soluble vitamins tend to

Edema Swelling (usually of the legs and feet, but can also extend throughout the body) due to an accumulation of extracellular fluid.

Steroid Hormones Hormones such as progesterone, estrogen, and testosterone produced primarily from cholesterol.

Table 4.8 Normal changes in maternal physiology during pregnancy^10,11 Blood Volume Expansion

Blood volume increases 20%

•

Plasma volume increases 50%

•

Edema (occurs in 60–75% of women)

•

Hemodilution

Concentrations of most vitamins and minerals

•

in blood decrease Blood Lipid Levels

Increased concentrations of cholesterol, LDL

•

cholesterol, triglycerides, HDL cholesterol Blood Glucose Levels

Increased insulin resistance (increased plasma

•

levels of glucose and insulin) Maternal Organ and Tissue Enlargement

Heart, thyroid, liver, kidneys, uterus, breasts,

•

adipose tissue Circulatory System

Increased cardiac output through increased heart

•

rate and stroke volume (30–50%) Increased heart rate (16% or 6 beats/min)

•

Decreased blood pressure in the first half of

•

pregnancy (29%), followed by a return to nonpregnancy levels in the second half Respiratory System

Increased tidal volume, or the amount of air

•

inhaled and exhaled (30–40%) Increased oxygen consumption (10%)

•

Food Intake

Increased appetite and food intake; weight gain

•

Taste and odor changes, modification in preference

•

for some foods Increased thirst

•

Gastrointestinal Changes

Relaxed gastrointestinal tract muscle tone

•

Increased gastric and intestinal transit time

•

Nausea (70%), vomiting (40%)

•

Heartburn

•

Constipation

•

Kidney Changes

Increased glomerular filtration rate (50–60%)

•

Increased sodium conservation

•

Increased nutrient spillage into urine; protein is conserved

•

Increased risk of urinary tract infection

•

Immune System

Suppressed immunity

•

Increased risk of urinary and reproductive tract infection

•

Basal metabolism

Increased basal metabolic rate in second half of pregnancy

•

Increased body temperature

• Hormones

Placental secretions of large amounts of hormones needed

•

to support physiological changes of pregnancy

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and for fetal structures to develop. Because normal fetal tissue growth and development are genetically timed, nu-trients must be available at the same time that genes con-trolling fetal growth and development are expressed.¹⁵ Carbohydrate Metabolism Many adjustments in car-bohydrate metabolism are made during pregnancy that promote the availability of glucose to the fetus. Glucose is the fetus’s preferred fuel, even though fats can be uti-lized for energy. Continued availability of a fetal supply of glucose is accomplished primarily through metabolic changes that promote maternal insulin resistance. These changes, sometimes referred to as the diabetogenic effect of pregnancy, make normal pregnant women slightly car-bohydrate intolerant in the third trimester of pregnancy.¹⁷ Illustration 4.4 provides an example of the normal levels of plasma glucose and insulin during late pregnancy com-pared to prepregnancy levels.

Carbohydrate metabolism in the first half of pregnancy is characterized by estrogen- and progesterone-stimulated increases in insulin production and conversion of glucose to glycogen and fat. In the second half, rising levels of hCS and prolactin from the mother’s pituitary gland inhibit the conversion of glucose to glycogen and fat.¹³ At the same time, insulin resistance builds in the mother, increasing her reliance on fats for energy. Decreased conversion of Table 4.9 Key placental hormones and examples

of their roles in pregnancy^13,16 Human chorionic gonadotropin (hCG)

Maintains early pregnancy by stimulating the corpus luteum to produce estrogen and progesterone. It stimulates growth of the endometrium. The placenta produces estrogen and progesterone after the first 2 months of pregnancy

Progesterone

Maintains the implant; stimulates growth of the endometrium and its secretion of nutrients; relaxes smooth muscles of the uterine blood vessels and gastrointestinal tract; stimulates breast development;

promotes lipid deposition Estrogen

Increases lipid formation and storage, protein

synthesis, and uterine blood flow; prompts uterine and breast duct development; promotes ligament flexibility Human chorionic somatotropin (hCS)

Increases maternal insulin resistance to maintain glucose availability for fetal use; promotes protein synthesis and the breakdown of fat for energy for maternal use

Leptin

May participate in the regulation of appetite and lipid metabolism, weight gain, and utilization of fat stores

needs are driven by genetically timed sequences of fetal tissue growth and development. The amount and types of nutrients required depend on the type and amount of nu-trients needed for specific metabolic pathways to function

10 20 30 40

2 3 4 5 6 7

200

50 100 150

5 10 15

Weeks

Serum Levels of hCG and hPL (mcg/ml) Plasma Levels of Progesterone (ng/ml) Plasma Levels of Estradiol (ng/ml)

hCG

hPL

Estradiol Progesterone

Illustration 4.3 Changes in maternal plasma concentration of hormones during pregnancy.

Glucose

Insulin

8 AM 1 PM 6 PM 8 AM

Meals

12 M

Nonpregnant (a = 8) Normal pregnant (a = 8)

Nonpregnant (a = 8) Normal pregnant (a = 8) 140

120

250

0 50 100 150 200 100

mg/dLmcU/ml

Illustration 4.4 Plasma glucose and insulin levels in nonpregnant women and in women near term.

a * indicates statistical significance.

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lipoproteins, phospholipids, and fatty acids also increase, but to a lesser extent than do triglycerides. The increased cholesterol supply is used by the placenta for steroid hormone synthesis, and by the fetus for nerve and cell-membrane formation.¹⁷

High concentrations of cholesterol and triglycerides ob-served during pregnancy do not promote the development of atherosclerosis (hardening of the arteries), as they may in adults.²⁰ Small increases in HDL cholesterol in preg-nancy appear to decline within a year postpartum and re-main lower than prepregnancy levels. It is speculated that declines in HDL cholesterol after pregnancy may contrib-ute to an increased risk of heart disease in women. Other changes in serum lipids appear to revert to prepregnancy levels postpartum.²²

By the third trimester of pregnancy, most women have a lipid profile that would be considered atherogenic, if not for pregnancy. These blood lipid changes are normal, however, which is why blood lipid screening is not rec-ommended during pregnancy.²² Normal changes in blood lipid levels during pregnancy appear to be unrelated to maternal dietary intake.²³

Mineral Metabolism Impressive changes in mineral metabolism occur during pregnancy. Calcium metabo-lism is characterized by an increased rate of bone turn-over and reformation.¹⁴ Elevated levels of body water and tissue synthesis during pregnancy are accompanied by increased requirements for sodium and other minerals.

Sodium metabolism is delicately balanced during preg-nancy to promote an accumulation of sodium by the mother, placenta, and fetus. This is accomplished by changes in the kidneys that increase aldosterone secretion and the retention of sodium. This normal change in preg-nancy renders ineffective and potentially harmful any at-tempts to prevent and treat high blood pressure in pregnancy by reducing sodium intake. Sodium restriction may overstress mechanisms that act to conserve sodium and lead to functional and growth impairments due to sodium depletion.²⁴

glucose to glycogen and fat, lowered ma-ternal utilization of glucose, and increased liver production of glucose help to ensure that a constant supply of glucose for fetal growth and development is available in the second half of pregnancy.

Fasting maternal blood glucose lev-els decline in the third trimester due to increased utilization of glucose by the rapidly growing fetus. However, postmeal blood glucose concentrations are elevated and remain higher longer than before pregnancy.¹⁷

Accelerated Fasting Metabolism Maternal metabo-lism is rapidly converted toward glucogenic amino acid utilization, fat oxidation, and increased production of ketones with fasts that last longer than 12 hours. Decreased levels of plasma glucose and insulin and increased lev-els of triglycerides, free fatty acids, and ketones are seen hours before they occur in nonpregnant fasting women.

The rapid conversion to fasting metabolism allows preg-nant women to use primarily stored fat for energy while sparing glucose and amino acids for fetal use.¹⁷

Although these metabolic adaptations help ensure a constant fetal supply of glucose, fasting eventually in-creases the dependence of the fetus on ketone bodies for energy. Prolonged fetal utilization of ketones, such as oc-curs in women with poorly controlled diabetes or in those who lose weight during part or all of pregnancy, is associ-ated with reduced growth and impaired intellectual devel-opment of the offspring.¹⁸

Protein Metabolism Nitrogen and protein are needed in increased amounts during pregnancy for synthesis of new maternal and fetal tissues. It is estimated that 925 grams (2 pounds) of protein is accumulated during pregnancy.¹⁹ To some extent the increased need for protein is met through reduced levels of nitrogen excretion and the con-servation of amino acids for protein tissue synthesis. There is no evidence, however, that the mother’s body stores protein early in pregnancy in order to meet fetal needs for protein later in pregnancy. Maternal and fetal needs for protein are primarily fulfilled by the mother’s intake of protein during pregnancy.¹²

Fat Metabolism Multiple changes occur in the body’s utilization of fats during pregnancy. Overall, changes in li-pid metabolism promote the accumulation of maternal fat stores in the first half of pregnancy and enhance fat mobi-lization in the second half.¹⁰ In addition to seeing increas-ing maternal reliance on fat stores for energy as pregnancy progresses, we see blood levels of many lipoproteins in-crease dramatically (Table 4.10). Plasma triglyceride levels increase first and most dramatically, reaching three times nonpregnant levels by term.^12,17 Cholesterol-containing

Glucogenic Amino Acids Amino acids such as alanine and glutamate that can be converted to glucose.

Ketones Metabolic by-products of the breakdown of fatty acids in energy formation. b-hydroxybutyric acid, acetoacetic acid, and acetone are the major ketones, or “ketone bodies.”

Table 4.10 Changes in cholesterol and triglyceride levels during pregnancy^21,22

Trimester

Cholesterol

mmol/L (mg/dL)

Triglycerides

mmol/L (mg/dL)

1 5.78 (223) 1.19 (105)

2 6.88 (266) 1.32 (117)

3 8.14 (314) 2.58 (228)

Nonpregnant 5.11 (197) 0.80 (71)

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fetal and maternal blood until delivery, when ruptures in blood vessels may occur.

Nutrient Transfer The placenta uses 30–40% of the glucose delivered by the maternal circulation. If nutrient supply is low, the placenta fulfills its needs before nutri-ents are made available to the fetus. If nutrient supplies fall short of meeting placental needs, functioning of the placenta is compromised to sustain the nutrient supply and health of the mother.²⁵

Nutrient transfer across the placenta depends on a number of factors, including:

The size and the charge of molecules available for

●

transport

Lipid solubility of the particles being transported

●

The concentration of nutrients in maternal and

●

fetal blood

Small molecules with little or no charge (water, for ex-ample) and lipids (cholesterol and ketones, for instance) pass through the placenta most easily, while large mole-cules (e.g., insulin and enzymes) aren’t transferred at all.

Nutrient exchange between the mother and fetus is un-regulated for some nutrients, oxygen, and carbon dioxide;

it is highly regulated for other nutrients. Nutrient transfer based on concentration gradients determined by the lev-els of the nutrient in the maternal and the fetal blood is unregulated. In these cases, nutrients cross placenta mem-branes by simple diffusion from blood with high concen-tration of the nutrient to blood with lower concenconcen-tration.

Three primary mechanisms regulate nutrient trans-fer: facilitated diffusion, active transport, and endocytosis (or pinocytosis). Table 4.11 summarizes mechanisms of

The Placenta

The word placenta is derived from the Latin word for cake. The placenta, with its round, disklike shape (Illustration 4.5), looks somewhat like a cake—the more so the more active the imagination. The placenta devel-ops from embryonic tissue and is larger than the fetus for most of pregnancy. Development of the placenta precedes fetal development.

Functions of the placenta include:

Hormone and enzyme production,

●

Nutrient and gas exchange between the mother

●

and fetus

Removal of waste products from the fetus

●

Its structure, including a double lining of cells separating maternal and fetal blood, acts as a barrier to some harmful compounds, and it governs the rate of passage of nutrients and other substances into and out of the fetal circulation (Illustration 4.6). The barrier role of the placenta is bet-ter described as a fence than as a filbet-ter that guards the fetus against all things harmful. Many potentially harm-ful substances (alcohol, excessive levels of some vitamins, drugs, and certain viruses, for example) do pass through the placenta to the fetus. The placenta is a barrier to the passage of maternal red blood cells, bacteria, and many large proteins. The placenta also prevents the mixing of

Illustration 4.6 Structure of the placenta. Maternal arteries and veins are part of the maternal circulation, whereas umbilical arteries and veins are part of the fetal circulation. Blood enters the fetus through umbilical veins and exits through umbilical arteries.

Umbilical vein

Umbilical artery

Maternal artery Maternal side Fetal side

Maternal vein Umbilical cord

Pool of maternal blood

Illustration 4.5 A placenta.

Educational Images Ltd./Custom Medial Stock - www.cmsp.com

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Dalam dokumen Through the Life Cycle (Halaman 119-125)