Adaptation of the maternal organism to pregnancy

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

[1], [2], [3], [4], [5], [6]

Changes in the cardiovascular system during pregnancy:

• The volume of circulating blood (BCC) varies from 6 weeks of pregnancy, increasing by an average of 40-50%. BCC grows rapidly to 20-24 weeks and remains at this level until delivery;
• In connection with the increase in BCC, cardiac output is increased by 40%; increased heart rate and stroke volume by 30-40%. Arterial pressure and resistance of the vascular wall are reduced to about the middle of pregnancy, and then in the third trimester, blood pressure increases to the level outside of pregnancy.

[7], [8], [9], [10], [11]

In pregnancy, significant hematologic changes occur

• The volume of plasma increases;
• The number of blood cells increases. The level of erythrocytes is increased, but the volume of plasma grows three times more than the volume of erythrocytes. There is a dilution of blood, a physiological "anemia". Lower normal hemoglobin level 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 there is a shift in the norm of blood to the immature (rod) cells;
• Platelet level practically does not change and is normal, 140-400x10 ⁹ cells / l;
• Factors of blood coagulation significantly increase during pregnancy. Especially factor VIII and fibrinogen, the activity of the fibrinolytic system decreases - this leads to hypercoagulation and increases the risk of thrombosis;
• The ESR increases.

Changes in the breathing system

• The need for oxygen increases by 20%, P02 does not change;
• The volume of air changed by breathing increases by 40%, the residual volume decreases by 20%;
• The pH of the blood does not change;
• In connection with increased ventilation pCO2 decreases to 28-32 mm Hg. (increased ventilation occurs under the influence of progesterone);
• Anatomical changes: the chest angle is somewhat widened and the diaphragm rises higher.

[12], [13], [14], [15], [16]

Physiological changes in kidney function during pregnancy

• Anatomical changes: the size of the kidneys increases by 1.0-1.5 cm, the pelvis, glomeruli and ureters widen (this leads to predisposition to pyelonephritis);
• Functional changes: the flow of plasma through the kidneys increases by 50-80% in the I and II trimesters and slightly decreases in the III trimester (by reducing the level of creatinine and urea); Glucosuria can be at a normal level of sugar in the blood; electrolytes of blood serum indicate an average level of respiratory alkalosis.

Changes in the hepatobiliary system during pregnancy

In connection with the increase in the volume of circulating blood, the majority of liver function indicators may differ from their level in non-pregnant ones. In the liver, the synthesis of a large class of proteins (with the exception of immunoglobulins), the synthesis of fibrinogen, prothrombin, clotting factors (V, VII, X, XI, XII, XIII), fibrinolytic factors (antithrombin III, proteins C and S) occurs. Of the hepatic enzymes in the serum, only alkaline phosphatase is increased. The remaining hepatic enzymes (serum transaminases, bilirubin, y-glutamine-transpeptidase) do not change in the physiological course of pregnancy.

[17], [18], [19], [20], [21], [22], [23], [24]

Changes in the digestive system during pregnancy

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

[25], [26], [27], [28], [29]

Significant changes occur in the central nervous system during physiological pregnancy

According to many authors, in almost healthy women with normal pregnancy increases the number of psychoasthenic, neurasthenic and vegetovascular changes. Psycho-emotional behavior of women is changing. In the first half of pregnancy, along with the appearance of a certain inhibition and changes in perception of the surrounding world (taste, smell), mood disorders are noted, its fluctuations easily appear, inadequate to external influence. The increased joyful mood can sharply decrease, there is tearfulness, irritability, suspiciousness, increased suggestibility. After the appearance of fetal movement, motivation of motherhood is formed, motivation is changed due to different reasons. At the end of pregnancy there is a high level of depressive disorders.

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

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

In connection with pregnancy, significant changes occur in the endocrine organs of the mother

Over the past 50 years, numerous studies of endocrine and physiological changes in the body of women during pregnancy have revealed thin mechanisms for the regulation of these functions, the role of the fetus and placenta in maintaining the process of pregnancy. Growth of the fetus depends on the intensity and effectiveness of metabolic processes in the mother's body, including the characteristics of new endocrine relationships.

Steroidogenesis in pregnancy can not be regarded as a derivative of one organ, it is a whole system in which the mother-placenta-fetus system participates.

From the point of view of steroid biosynthesis, the placenta and the fetus alone are imperfect systems, since both do not have certain enzymes necessary for the synthesis of steroids. Three enzyme 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 the fetus:

• placenta;
• adrenal cortex of the fetus;
• the fetal liver, which is the main source of cholesterol in the fetal blood (maternal cholesterol penetrates to the fetus in small amounts). The embryonic liver contains a very active system of 16a-hydroxylase;
• the adrenal cortex of the mother produces DEA, which is the precursor of estrone and estradiol; produces cortisol, which, passing through the placenta, turns into cortisone; the mother's liver is the source of cholesterol, the most important source of progesterone synthesis; 1balfa-DEA, conjugates placental steroids.

Progesterone and pregnancy

Progesterone is an intermediate link in the biosynthesis of estrogens and androgens in the ovaries, adrenals and in the placenta. The main amount of progesterone is formed in the placenta from the mother's cholesterol. Cholesterol is converted into pregnenolone. Under the action of A 4- u, A 5 isomerase, Zbeta-ol dehydrogenase, pregnenolone is converted to progesterone. The progesterone synthesized in the placenta falls into the adrenal cortex of the fetus and the mother, where it is converted to aldosterone, 17a-hydroxyprogesterone and cortisol. The adrenal cortex of the fetus does not contain Zbeta-hydroxysteroid dehydrogenase and can not synthesize progesterone from pregnenolone. The content of progesterone in the blood is small. Before 7 weeks of pregnancy, the main source of progesterone is the yellow body of pregnancy. After 10 weeks, the main source of synthesis of progesterone is the placenta. In the first weeks of pregnancy, the level of progesterone is at the level of the II phase of the menstrual cycle. During the peak of the chorionic gonadotropin at 5-7 weeks of gestation, the progesterone level decreases, The production of hormones begins to fade in the yellow body, and the placenta has not yet gained its power in the production of this hormone. After 10 weeks of pregnancy, the level of progesterone rises. With 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 mother's bloodstream. Unlike estrogens, progesterone production does not depend on its predecessors, utero-placental perfusion, on the condition of the fetus and even on whether the fetus is alive or not. This is because the contribution of the fetus to the synthesis of progesterone is negligible. Decidua and membranes also synthesize and metabolize progesterone. The progesterone precursor in this synthesis is pregnenolone-sulfate.

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

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

Progesterone is one of the major hormones that inhibits the T-cell-mediated fetal rejection reaction. A high concentration of progesterone in the myometrium blocks the cellular immune response to foreign antigens.

The need for progesterone in maintaining pregnancy was shown in experiments in which interruption of pregnancy was induced by the administration of antibodies to progesterone. Miscarriage was prevented by the introduction of progesterone.

Estrogens and pregnancy

When pregnancy produces a large number of estrogens and after 5-7 weeks of gestation, most of the estrogen is produced in the placenta, namely in the syncytiotrophoblast. For the synthesis of estrogens in the placenta, it is necessary to receive from the body of the mother and fetus predecessors. Estrogens are produced in the placenta due to a very powerful p450 aromaenzyme system. Thanks to this system, estrogens from the androgen are synthesized in the placenta, DEAS, which comes from the fetus, is converted to DEA by sulphatase in the placenta, then to androstenedione-testosterone-estrone and 17beta-estradiol.

Dehydroepiandrosterone sulfate is desulfurized in the placenta by sulfatase to androstenedione. The product of aromatization of androstenedione is estrone, which under the action of 17β-hydroxysteroid dehydrogenase type I is converted to estradiol. It is suggested that this enzymatic activity is not in the trophoblast, but in the walls of the vessels of the placenta. This explains why estrone mostly returns to the fetus, and estradiol to the mother's bloodstream.

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

Estriol in the placenta is formed from precursors. DEAS from the adrenal glands goes to the fetal liver, where 16alpha-hydroxylation occurs and 1 balfa-hydroxydehydroepiandrosterone sulfate is formed. From this precursor in the placenta through aromatase activity, estriol is formed. After delivery in a newborn, 16-hydroxyl activity quickly disappears. Estriol in maternal blood is conjugated with the formations of sulfates and glucuronides and sulfoglucuronide estriol and excreted in the urine.

The researchers noted that the contribution of the mother to the synthesis of estrogens is negligible. So it was found that with anencephaly of the fetus, when there are no normal adrenal glands of the fetus, the level of estrogens is extremely low. The adrenal glands of the fetus play a key role in the synthesis of estrogens. At full-term pregnancy, the adrenal glands of the fetus are about the same as those of an adult human and weigh 8-10 g or more. Morphologically they consist of a fetal zone occupying 85% of the gland, and the cortex proper, which occupies only 15% of the gland, and it is from this part that the adrenal glands of the child are formed. The adrenal glands of the fetus have a powerful steroidogenesis. At full term, they secrete from 100 to 200 mg / dl of steroids, while the adult produces only about 35 mg / dl.

The adrenal glands of the fetus participate in biochemical processes leading to the maturation of the fetal testicles and in the delivery of labor, so the regulation of steroidogenesis is extremely important in the development of pregnancy. To date, the issue of regulating steroidogenesis by the adrenal glands has not been resolved, although numerous studies have been carried out. 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 the chorionic gonadotropin. It was suggested that fruit prolactin stimulates the growth and steroidogenesis of the adrenal glands, as it increases in parallel with their development, but in experimental studies this has not been confirmed, moreover, the level of steroidogenesis did not diminish when treating pregnant women with parlodel. There were suggestions about the trophic role of growth hormone, growth factors. It is possible that in the placenta locally unidentified growth factors are formed.

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

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

The adrenal glands also synthesize inhibin and activin. Activin strengthens the action of ACTH, and inhibin inhibits the mitogenesis of adrenal cells. Actinin in experiments contributed to the adrenal cell transition to the synthesis of DEAC on the synthesis of cortisol. Apparently, activin takes part after birth in the remodeling of the adrenal fruit zone.

It is also believed that in the regulation of steroidogenesis in the adrenal glands, estrogens participate and, on the basis of feedback, direct steroidogenesis towards the formation of DEAC. After childbirth, with a decrease in the level of estrogen, the adrenal glands of the fetus pass to the type of hormonal production that is characteristic of adults.

Estrogen levels in the mother are defined 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 definition is not of great clinical significance.
2. Estradiol appears in the 6-8 weeks of pregnancy and also varies widely from 6 to 40 ng / ml, half of the fruit, half of the parentage.
3. Estriol begins to produce from 9 weeks, gradually increases, reaches a plateau in 31-35 weeks, and then again increases.

If during pregnancy estrogen and estradiol levels increase 100 times, then the level of estriol increases a thousand times.

Extremely great role of estrogens in pregnancy:

• affect all biochemical processes in the uterus;
• cause the growth of vessels in the endometrium, increase the flow of blood to the uterus. It is believed that the increase in blood flow in the uterus is the main function of estriol and is associated with activation of the synthesis of prostaglandins;
• increase tissue oxygen uptake, energy metabolism, enzyme activity, and nucleic acid synthesis;
• play an important role in nidation of the fruit egg;
• increase the sensitivity of the uterus to oxytetics;
• are of great importance in water-salt metabolism, etc.

[30], [31], [32]