Adaptation of the maternal body to pregnancy

Pregnancy places great demands on a woman's body. To ensure the vital functions, growth and development of the fetus, significant changes occur in the mother's body, which affect almost all body systems.

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Changes in the cardiovascular system during pregnancy:

• The circulating blood volume (CBV) changes from 6 weeks of pregnancy, increasing on average by 40-50%. CBV increases rapidly up to 20-24 weeks and remains at this level until delivery;
• Due to the increase in circulating blood volume, cardiac output increases by 40%; heart rate and stroke volume increase by 30-40%. Blood pressure and vascular wall resistance decrease until about mid-pregnancy, and then in the third trimester, blood pressure increases to the level outside pregnancy.

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During pregnancy, significant hematological changes occur.

• The plasma volume increases;
• The number of formed elements of the blood increases. The level of erythrocytes is increased, but the volume of plasma increases three times more than the volume of erythrocytes. Blood dilution occurs, physiological "anemia". The lower normal level of hemoglobin is 100 g / l or 30% hematocrit;
• The total number of white blood cells increases. The total level of leukocytes and lymphocytes is 9-15x10 ⁹ cells/l, sometimes even in the norm there is a shift in the blood formula towards immature (rod) cells;
• The platelet level remains virtually unchanged and is normal, 140-400x10 ⁹ cells/l;
• Blood coagulation factors increase significantly during pregnancy. Especially factor VIII and fibrinogen, the activity of the fibrinolytic system decreases - this leads to hypercoagulation and increases the risk of thrombosis;
• ESR increases.

Changes in the respiratory system

• Oxygen demand increases by 20%, P02 does not change;
• The volume of air changed during breathing increases by 40%, the residual volume decreases by 20%;
• Blood pH does not change;
• Due to increased ventilation, pCO2 decreases to 28-32 mm Hg (increased ventilation occurs under the influence of progesterone);
• Anatomical changes: the sternal angle is slightly widened and the diaphragm rises higher.

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Physiological changes in kidney function during pregnancy

• Anatomical changes: the size of the kidneys increases by 1.0-1.5 cm, the renal pelvis, glomeruli and ureters expand (this leads to a predisposition to pyelonephritis);
• Functional changes: plasma flow through the kidneys increases by 50-80% in the first and second trimesters and decreases slightly in the third trimester (due to a decrease in creatinine and urea levels); glucosuria may occur with normal blood sugar levels; serum electrolytes indicate a moderate level of respiratory alkalosis.

Changes in the hepatobiliary system during pregnancy

Due to the increase in the volume of circulating blood, most liver function parameters may differ from their levels in non-pregnant women. The liver synthesizes a large class of proteins (except immunoglobulins), fibrinogen, prothrombin, blood coagulation factors (V, VII, X, XI, XII, XIII), fibrinolytic factors (antithrombin III, proteins C and S). Of the liver enzymes, only alkaline phosphatase is increased in the blood serum. The remaining liver enzymes (serum transaminases, bilirubin, y-glutamine transpeptidase) do not change during the physiological course of pregnancy.

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Changes in the Digestive System During Pregnancy

Nausea and vomiting are observed in 85% of pregnant women. The nature of this phenomenon is unclear, it is observed from 6 to 16 weeks of pregnancy and is not associated with pathology of either the mother or the fetus. 70% of pregnant women experience "heartburn" due to increased gastroesophageal reflux, due to the high position of the diaphragm.

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Significant changes also occur in the central nervous system during physiological pregnancy.

According to many authors, the number of psychoasthenic, neurasthenic and vegetative-vascular changes increases in practically healthy women with a normal pregnancy. The psycho-emotional behavior of women changes. In the first half of pregnancy, along with the appearance of some inhibition and changes in the perception of the surrounding world (taste, smell), mood disorders are noted, its fluctuations, inadequate to external influences, easily occur. An increased joyful mood can sharply decrease, tearfulness, irritability, suspiciousness, increased suggestibility appear. After the appearance of fetal movement, the motivation for motherhood is formed, motivations due to various reasons change. At the end of pregnancy, a high level of depressive disorders is observed.

It is believed that emotional reactions during pregnancy should be divided into two groups:

1. women who experience anxiety as a reaction to pregnancy and
2. women for whom the anxiety reaction is a characteristic feature of the personality, and an increase in anxiety and emotional excitability is associated with pregnancy. Emotional factors affect the state of the hypothalamus-pituitary system, target organs, which may lead to complications during pregnancy. This is especially true for women with a burdened obstetric history. In the early stages of pregnancy, an increase in the excitability of the cerebral cortex and activation of the reticular structures of the midbrain are noted. As pregnancy progresses, the excitability of the cerebral cortex decreases, the activity of synchronizing subcortical structures increases. These fluctuations in the activity of various brain formations do not go beyond the physiological parameters and the EEG pattern does not have pathological changes.

During pregnancy, significant changes occur in the mother's endocrine organs.

Over the past 50 years, numerous studies of endocrine and physiological changes in a woman's body during pregnancy have revealed subtle mechanisms for regulating these functions, and the role of the fetus and placenta in maintaining the pregnancy process has been determined. The growth and development of the fetus depend on the intensity and effectiveness of metabolic processes in the mother's body, including the characteristics of new endocrine relationships.

Steroidogenesis during pregnancy cannot be considered as a derivative of one organ; it is a whole system in which the mother-placenta-fetus system takes part.

From the point of view of steroid biosynthesis, the placenta and fetus separately represent imperfect systems, since both lack certain enzymes necessary for steroid synthesis. Three enzymatic systems "mother-placenta-fetus" work, complementing each other, as a single functional hormonal system, which is based on the interaction of the organs of the mother and fetus:

• placenta;
• fetal adrenal cortex;
• fetal liver, which is the main source of cholesterol in fetal blood (maternal cholesterol reaches the fetus in small amounts). Embryonic liver contains a very active 16a-hydroxylase system;
• The maternal adrenal cortex produces DHEA, which is a precursor of estrone and estradiol; produces cortisol, which, passing through the placenta, is converted into cortisone; the maternal liver is a source of cholesterol, the most important source of progesterone synthesis; 1-alpha-DHEA, conjugates placental steroids.

Progesterone and pregnancy

Progesterone is an intermediate link in the biosynthesis of estrogens and androgens in the ovaries, adrenal glands and placenta. The main amount of progesterone is formed in the placenta from maternal cholesterol. Cholesterol is converted into pregnenolone. Under the action of A4- and A5-isomerase, 3beta-ol-dehydrogenase, pregnenolone is converted into progesterone. Progesterone synthesized in the placenta enters the adrenal cortex of the fetus and mother, where it is converted into aldosterone, 17a-hydroxyprogesterone and cortisol. The adrenal cortex of the fetus does not contain 3beta-hydroxysteroid dehydrogenase and cannot synthesize progesterone from pregnenolone. The content of progesterone in the blood is low. Up to 7 weeks of pregnancy, the main source of progesterone is the corpus luteum of pregnancy. After 10 weeks, the main source of progesterone synthesis is the placenta. In the first weeks of pregnancy, the progesterone level is at the level of phase II of the menstrual cycle. During the peak of chorionic gonadotropin in the 5-7 weeks of pregnancy, the progesterone level decreases, since the production of hormones in the corpus luteum begins to fade, and the placenta has not yet gained its capacity in the production of this hormone. After 10 weeks of pregnancy, the progesterone level increases. In full-term pregnancy, the placenta is able to synthesize up to 250 mg of progesterone. Most of the progesterone produced by the placenta enters the maternal bloodstream. Unlike estrogens, progesterone production does not depend on precursors, uteroplacental perfusion, the condition of the fetus, or even whether the fetus is alive or not. This is because the contribution of the fetus to progesterone synthesis is insignificant. Progesterone is also synthesized and metabolized in the decidua and membranes. The precursor of progesterone in this synthesis is pregnenolone sulfate.

The progesterone level in the amniotic fluid is highest at 10-20 weeks of pregnancy, then gradually decreases. The progesterone level in the myometrium is 3 times higher than in the mother's plasma in early pregnancy and remains the same as in plasma during full-term pregnancy. Progesterone in plasma is converted into a number of biologically active products: deoxycorticosterone (DOS), dehydroprogesterone. It is believed that these metabolites participate in maintaining the refractoriness of the mother's body to the action of angiotensin II. The DOS content during full-term pregnancy is 1200 times higher than before pregnancy. Placental progesterone is a source for the synthesis of cortisol and aldosterone by the adrenal glands of the fetus.

It is believed that progesterone plays an extremely important role during pregnancy. Even before fertilization, progesterone causes decidual transformations of the endometrium and prepares it for implantation; promotes the growth and development of the myometrium, its vascularization; maintains the myometrium in a state of rest, by neutralizing the action of oxytocin; synthesizes the growth and development of the mammary glands.

Progesterone is one of the main hormones that inhibits the T-lymphocyte-mediated fetal rejection reaction. High concentrations of progesterone in the myometrium block the cellular immune response to foreign antigens.

The necessity of progesterone in maintaining pregnancy was demonstrated in experiments in which abortion was induced by the introduction of antibodies to progesterone. Miscarriage was prevented by the introduction of progesterone.

Estrogens and pregnancy

During pregnancy, a large amount of estrogens is formed and after 5-7 weeks of pregnancy, almost the majority of estrogens are produced in the placenta, namely in the syncytiotrophoblast. For the synthesis of estrogens in the placenta, it is necessary to receive precursors from the mother and fetus. Estrogens are produced in the placenta due to a very powerful p450 aroenzyme system. Thanks to this system, estrogens are synthesized in the placenta from androgens - DHEAS, coming from the fetus, is converted into DHEA under the action of sulfatase in the placenta, then into androstenedione - testosterone - estrone and 17beta-estradiol.

Dehydroepiandrosterone sulfate is desulfurized in the placenta by sulfatase to androstenedione. The product of androstenedione aromatization is estrone, which is converted to estradiol by 17beta-hydroxysteroid dehydrogenase type I. It is believed that this enzymatic activity is not located in the trophoblast, but in the walls of the placental vessels. This explains why estrone is mainly returned to the fetus, and estradiol to the maternal circulation.

But the main estrogen during pregnancy is not estrone and estradiol, but estriol. Estriol has low activity, since it is secreted in very large quantities, but this effect is more significant than other estrogens.

Estriol in the placenta is formed from precursors. DHEAS from the fetal adrenal glands enters the fetal liver, where 16alpha-hydroxylation occurs and 1-alpha-hydroxydehydroepiandrosterone sulfate is formed. Estriol is formed from this precursor in the placenta via aromatase activity. After birth, 16-hydroxyl activity quickly disappears in the newborn. Estriol in the maternal blood is conjugated to form sulfates and glucuronides and sulfoglucuronides of estriol and is excreted in the urine.

Researchers have noted that the mother's contribution to estrogen synthesis is insignificant. Thus, it was found that in fetal anencephaly, when normal fetal adrenal glands are absent, the estrogen level is extremely low. The fetal adrenal glands play a key role in estrogen synthesis. In full-term pregnancy, the fetal adrenal glands are approximately the same as those of an adult and weigh 8-10 g or more. Morphologically, they consist of a fetal zone, which occupies 85% of the gland, and the cortex itself, which occupies only 15% of the gland, and it is from this part that the child's adrenal glands will form. The fetal adrenal glands have powerful steroidogenesis. In full-term pregnancy, they secrete from 100 to 200 mg / dl of steroids, while an adult produces only about 35 mg / dl.

The fetal adrenal glands participate in biochemical processes leading to the maturation of the fetal testicles and induction of labor, therefore the regulation of steroidogenesis is extremely important in the development of pregnancy. Until now, the issue of regulation of steroidogenesis by the adrenal glands has not been resolved, although numerous studies have been conducted. The leading role in steroidogenesis belongs to ACTH, but at the beginning of pregnancy the adrenal glands grow and begin to function without ACTH, possibly under the influence of chorionic gonadotropin. It was assumed that fetal prolactin stimulates the growth and steroidogenesis of the adrenal glands, since it increases in parallel with their development, but this was not confirmed in experimental studies, moreover, when pregnant women were treated with parlodel, the level of steroidogenesis did not decrease. Assumptions were made about the trophic role of growth hormone, growth factors. It is possible that unidentified growth factors are locally formed in the placenta.

The precursors of steroidogenesis in the adrenal glands are low-density lipoproteins (LDL), which are stimulated by ACTH through an increase in LDL receptors.

In the fetal adrenal glands, insulin-like growth factors (IGF-I and IGF-II) are extremely important in transmitting the trophic action of ACTH, especially IGF-II, the production of which is stimulated by ACTH.

The adrenal glands also synthesize inhibin and activin. Activin enhances the action of ACTH, and inhibin inhibits mitogenesis of adrenal cells. In experiments, activin promoted the transition of adrenal cells from synthesis of DHEAS to synthesis of cortisol. Apparently, activin takes part in remodeling of the fetal zone of the adrenal glands after birth.

It is also believed that estrogens participate in the regulation of steroidogenesis in the adrenal glands and, according to the principle of feedback, direct steroidogenesis towards the formation of DHEAS. After birth, with a decrease in the level of estrogens, the adrenal glands of the fetus switch to the type of hormonal production that is characteristic of adults.

Estrogen levels in the mother's body are determined as follows.

1. Estrone begins to be produced from 6-10 weeks of pregnancy. By the end of pregnancy, its level is in a wide range from 2 to 30 ng/ml and its determination does not have much clinical significance.
2. Estradiol appears at 6-8 weeks of pregnancy and also fluctuates widely from 6 to 40 ng/ml, half of fetal and half of maternal origin.
3. Estriol begins to be produced at 9 weeks, gradually increases, reaches a plateau at 31-35 weeks, and then increases again.

If during pregnancy the levels of estrone and estradiol increase 100-fold, then the level of estriol increases a thousand-fold.

The role of estrogens during pregnancy is extremely important:

• affect all biochemical processes in the uterus;
• cause proliferation of blood vessels in the endometrium, increase blood flow to the uterus. It is believed that increased blood flow in the uterus is the main function of estriol and is associated with the activation of prostaglandin synthesis;
• enhance oxygen absorption by tissues, energy metabolism, enzyme activity and nucleic acid synthesis;
• play an important role in the nidation of the fertilized egg;
• increase the sensitivity of the uterus to oxytotic substances;
• are of great importance in water-salt metabolism, etc.

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