Maternal Physiological & Endocrinological Changes in Pregnancy
Although the anatomical and physiological changes that occur during pregnancy chiefly involve the genital tract and the breasts, many other changes occur in other systems of the body.Endocrine changes:
Placental proteins and hormones mostly increase in concentration in the blood through pregnancy. Some, like human chorionic gonadotrophin (hCG) are early pregnancy agents; after peaking at the time of their maximum need, their levels are reduced.Oestrogen and progesterone influence ovarian and pituitary function, maintain the decidua, initiate the growth of the myometrium, increase the vascularity of the whole genital tract and cause proliferation of the glandular tissue of the breasts. These substances have secondary effects, including the retention of water in the body, relaxation of smooth muscles, and possibly relaxation of pelvic ligaments.
Hormones produced within the pregnant uterus:
Human chorionic gonadotrophin (hCG).
Human placental lactogen (hPL).
Gonadotrophin releasing hormone (GnRH).
Corticotrophin releasing factor (CRF).
Prolactin.
Human growth hormone (hGH).
Adrenocorticotrophin hormone (ACTH).
Insulin-like growth factor I & II.
1, 25 dihydroxycholecalciferol.
Parathyroid hormone related peptide.
Renin.
Angiotensin II.
Steroids (oestrogen & progesterone).
The trophoblast produces large amounts of hCG, particularly in the first trimester of pregnancy. High concentrations of this substance prolong the lifespan of the corpus luteum (for at least 8-10 wk.), this in turn continues to produce oestrogen and progesterone and so to maintain the uterine decidua until the output of oestrogen and progesterone from the placenta rises.
Embryonic development can also be reflected in the maternal blood stream by changes in serum concentrations of alpha-fetoprotein (AFP) which in pregnancy is derived from endodermal tissues. AFP and other substances of embryonic origin are present in the highest concentrations in amniotic fluid and in lesser amounts in maternal peripheral blood.
The common symptoms of pregnancy – morning sickness, breast changes and urinary frequency- which happen early in the first trimester are most likely to be caused by the hormonal changes.
Oestrogen stimulates synthesis of prolactin by the pituitary gland, but together with progesterone it inhibits the lactogenic effect of human placental lactogen (hPL)(which is produced from the placenta) and prolactin.
During pregnancy the anterior lobe of the pituitary gland undergoes hypertrophy, with an increase of both acidophil and basophil cells due to the influence of increased oestrogen. No anatomical changes are evident in the posterior lobe of the pituitary gland.
FSH & LH are suppressed by (hCG). Human growth hormone from anterior pituitary gland is suppressed during pregnancy by (hPL).
There is increase in plasma insulin concentrations with insulin resistance by the activity of (hPL) or other growth related hormones which reduce peripheral insulin sensitivity.
The thyroid gland is slightly enlarged during pregnancy, and the basal metabolic rate is increased. (hCG) has a thyrotrophic function, TSH may be suppressed during the 1st trimester of pregnancy. Thyroid function is considered to remain normal throughout the remainder of pregnancy. There is increase in thyroid-binding globulin & increase in the bound forms of thyroxin (T4) & (T3), but the circulatory concentrations of unbound (active) forms are essentially unaltered.
There is increased concentration of adrenal hormones in both the blood and the urine. There is also some increase in the excretion of mineralocorticoids (aldosterone).
The uterus:
The uterus is formed from fusion of the two Mullerian ducts in the midline. The uterus comprises three muscle layers. These are a thin, inner layer of circular muscle fibres; a thin, outer layer consisting of longitudinal muscle fibres, and a thicker, central layer of interlocking fibres.
During pregnancy the uterus is adapted to contain the growing fetus and placenta, and it also undergoes changes in preparation for expelling the fetus during labour. The changes include: 1. Development of the decidua, 2. Hypertrophy of the muscle coat,3. Increased vascularity, 4.formation of the lower segment and 5. Softening of the cervix.
At term the uterus is about 35cm long and 23cm in diameter. It weighs 1 kg ( in non-pregnant it weighs 50-60gr.). In early pregnancy uterine growth is a result of both hyperplasia and hypertrophy. As gestation increases myometrial cell division is less important and hypertrophy of individual cells accounts for most of the increase in uterine size. The uterine arteries also undergo hypertrophy in the first half of pregnancy. As well as changes in the size and number of myometrial cells, specialized cellular connections also develop with increasing gestation. The intercellular gap junctions allow changes in membrane potential to spread rapidly from one cell to another, facilitating the spread of membrane depolarization, and subsequent myometrial contraction. As these junctions mature, uterine contractions become more frequent. During pregnancy, the uterus contracts from time to time (Braxton Hicks contractions), and contractions can be stimulated by abdominal palpation. These contractions are not so strong or regular as those of labour, and are painless. The uterus is divided into the lower and upper segments. The lower segment is the part of the uterus and upper cervix. This part of the uterus contains less muscle and blood vessels, is thinner, and is the site of incision for the majority of caesarean sections.
The pregnant uterus is usually slightly rotated on its long axis, so that the anterior surface faces a little to the right.
The cervix:
The cervix becomes softer because of increased vascularity and a great increase in the gland spaces. The glands are distended with mucus, and the pattern of the glands becomes far more complex, so that the cervix seems to contain a honeycomb filled with mucus; described as a mucus plug. On inspection the cervix has a purple ting from venous congestion. The cervix remains elongated until the end of pregnancy, although in multiparae the external os tends to be patulous. Because of the great activity of the columnar epithelium of the cervix, and the increased secretion of mucus, it is common for the stratified epithelium on the vaginal surface of the cervix to be replaced by an outward extension of columnar epithelium- referred to as cervical ectropion. Such an appearance is not abnormal during pregnancy, and it will usually disappear in the puerperium.
The vagina and vulva:
The increased vascularity affects the vaginal walls, and they eventually show the purple coloration right down to the vulva. The vaginal walls become softened and relaxed, and the same change occurs in the perineal body. The total discharge from the vagina is increased (watery transudation from the vaginal wall + cervical mucus + desquamated vaginal cells). The vaginal secretion is acid in reaction (PH 4.5-5). As pregnancy advances the vulva shares in the increased vascularity and shows some swelling. Varicose veins may appear.
The breasts:
During pregnancy the secretion of oestrogen in large amounts causes thickening of the skin of the nipple and active growth and branching of the underlying ducts. The added action of progesterone causes proliferation of the glandular epithelium of the alveoli. Neither of these hormones causes the active secretion of milk, which only begins after delivery when the level of oestrogen falls and that of prolactin, from the anterior lobe of the pituitary gland, rises. The earliest change is a swelling of the breasts, especially at the periphery. The lobules of the gland can be felt easily and are harder than normal (producing knotty feeling in the breast). The breasts become a little tender, and the woman often describes a prickly sensation in them. The increased blood supply is shown by a very obvious network of veins under the skin. By about the 12th week of pregnancy the glands begin to secrete a clear fluid. Towards the end of pregnancy this secretion becomes more copious and is yellow in colour and creamy in consistence, it is then known as colostrum which consists of water, fat, albumin, salts and colostrum corpuscles.The nipple becomes larger and more erectile. The areolar skin is active and slightly raised above the surrounding skin. The areola often becomes pigmented (it persists as a permanent change). The sebaceous glands on the areola are very active in pregnancy, and can be seen as a ring of about 12 to 20 small tubercles ( Montgomery`s tubercles).
The abdominal wall:
The muscles of the abdominal wall become stretched to accommodate the enlarging uterus. In late pregnancy the umbilicus may be flattened out, or even protrude. Stretching of the abdominal skin may cause the formation of striae gravidarum. These are due to rupture of the elastic fibres of the skin, and they appear as curved lines, roughly concentric with the umbilicus, they may also be seen on the loins or thighs, and sometimes on the breasts. At first the striae are pink or red, but after delivery they become silvery-white. Pigmentation of the line from the pubes to the umbilicus (the linea nigra) may be seen, and may persist in part after the pregnancy.The pelvic joints:
The pelvic hyperaemia causes some softening and slight relaxation of the ligaments of the sacroiliac joints, and of the ligaments and fibrocartilage of the symphysis pubis, the mobility of which is slightly increased in pregnancy.Maternal metabolism during pregnancy:
Weight gain: The body weight increases during pregnancy. The total gain varies between 7 and 17 kg in normal cases, with an average of 12.5 kg. After the 12th week the average normal gain is about 0.35-0.45 kg per week. A fetus weighing 3.4 kg, a placenta of 0.65kg, amniotic fluid weighing 0.8 kg, a uterus of 1 kg, and an increase in the weight of the breasts of 0.8 kg would account for a total gain of 6.65 kg. The average additional gain of 6 kg represents the weight gained by the rest of the maternal tissues, due partly to fluid retention (1.5 kg), and partly due to increase in the body fat and protein.Metabolic changes: The basal metabolic rate during pregnancy is increased by 10-25%. Free thyroxin levels in the blood are normal or slightly reduced. During pregnancy the total need for calories is increased by 80,000 kcal, to maintain the fetus and additional maternal tissues. The renal threshold for the excretion of sugar from the blood is often lowered, so that glucose may appear in the urine although the blood sugar level is normal. Glycosuria is probably the result of increased glomerular filtration, which allows so much glucose to enter the tubules that they are unable to absorb it all. In spite of an increased excretion of amino acids during pregnancy, sufficient nitrogen is retained for the maternal and fetal needs.
There are also changes in lipid metabolism during pregnancy. Plasma levels of triglycerides, cholesterol and free fatty acids rise, and there is a greater tendency to ketosis.
An ordinary diet provides adequate amount of essential minerals and vitamins, but in the case of iron and calcium there is some risk of a deficit, particularly during the last trimester when the fetal uptake is greatest.
Changes in the blood during pregnancy:
The total blood volume is increased during pregnancy by about 30%. The uterine wall and the maternal blood spaces in the placenta contain a large volume of blood, perhaps 800ml. although the total number and volume of red cells increase by about 20%, the plasma volume increases by about 50%, with the result that the blood becomes more dilute and the red cell count and the haemoglobin concentration fall. A red cell count of 4 million per mm3 and a haemoglobin concentration of 11 g per 100ml are usually accepted as normal during pregnancy. The WBC count does not exceed 11000 per mm3. The platelet count is normal. The erythrocyte sedimentation rate is much increased during normal pregnancy.
Changes in the circulation during pregnancy:
The cardiac output rises from 4.5 L/ min to 6 L/ min during the first 10 weeks of pregnancy, remaining at the higher level until after delivery. The systolic blood pressure is unaltered during normal pregnancy but the diastolic pressure is reduced in the 1st and 2nd trimester, returning to non-pregnant levels by term. The pulse rate rises by between 8-16 beats per minute so that the greatly increased C.O. must be achieved by the expulsion of 70-80ml more blood from the heart at each beat. The heart is displaced upwards in late pregnancy and the apex is rotated outwards and the electrical axis is altered. There may be slight left axis deviation in an electrocardiograph, but there is little evidence of muscular hypertrophy. There is increased blood flow through the uterus and increased renal blood flow and some dilatation of peripheral vessels. The hands and feet are often noticeably warm during pregnancy, and the skin capillaries are dilated. The enlarged uterus interferes with the venous return from the legs. So that there is stasis in the large veins and slight oedema of the ankles may occur. Because of this interference with venous return, some women complain of faintness when lying on their backs (supine hypotension); haemorrhoids or varicose veins may appear for the first time of become worse during pregnancy. [Hb ↓, haematocrit ↓, WBC ↑, ESR ↑, fibrinogen conc. ↑ S.albumin conc.↓, pl.folate conc. ↓, heart rate ↑ (10-20%) 10-15 beats/ min, stroke vol. ↑ (10%), C.O.P.↑ (30-50%), renal blood flow ↑, mean arterial pressure ↓ (10%), peripheral resistance ↓ (35%)].
Changes in the respiratory system during pregnancy:
Pulmonary ventilation is increased by about 40%, as a result of increased tidal volume. Oxygen requirements only increase by 20% and the overbreathing leads to a fall in PCO2. The low PCO2 gives rise to a sensation of dyspnoea, which may be accentuated by elevation of the diaphragm. When the fetal head engages in the pelvis in late pregnancy this breathlessness diminishes. (tidal vol. ↑ (40%), vital capacity ↓, inspiratory capacity↑, functional residual capacity ↓, diaphragm raised, PCO2 ↓ (15-20%), PO2 ↑ (slight), PH alters little, bicarbonate excretion ↑.Changes in the alimentary tract during pregnancy:
The most striking change in the digestive function in pregnancy is nausea or morning sickness, which occurs in about a third of pregnancies. It begins at the 6th week and stops spontaneously before the 14th. Usually the symptoms are slight, excessive or prolonged vomiting is certainly pathological. Appetite and thirst increase during pregnancy, but minor digestive upsets are common, probably due to the relaxant effect of progesterone on smooth muscle. Sometimes gastric or intestinal distension occurs, and especially in early pregnancy this causes a feeling of abdominal enlargement. Heart burn is a common complaint, and is caused by relaxation of the cardiac sphincter of the stomach. The emptying time of the stomach is prolonged (this is of considerable importance in relation to the risk of vomiting during anaesthesia). The gastric acidity is often reduced. Constipation is not uncommon (constipation with pelvic hyperaemia and pressure of the enlarged uterus may lead to the formation or increase in size of haemorrhoids).Changes in the urinary tract during pregnancy:
There is progressive increase in the glomerular filtration rate and renal plasma flow, starting in early pregnancy and reaching 50% at term. A progressive fall in blood creatinine levels from 73μmol/ L to 47 at term occurs, and there is a similar fall in blood urea from 3.5 to 3.1 mmol/ L. Values considered normal in a non-pregnant woman may therefore indicate impaired renal function during pregnancy. The cumulative water retention in pregnancy is 7.5 L, together with 950 mmol sodium. This is due largely to increased aldosterone, renin and angiotensin I and II.Frequency of micturition occurs during the 1st 12 weeks, when the enlarging uterus is still in the pelvic cavity and presses on the bladder. It may also occur in the last month of pregnancy when the presenting part of the fetus is engaging in the pelvis.
From about the 16th week of pregnancy onwards there is considerable and progressive dilatation of the renal pelvis and of the ureters down as far as the level of the pelvic brim. The dilatation is chiefly caused by loss of muscle tone (by progesterone), although pressure from the uterus, displaced to the right by the descending colon, may explain the greater degree of change which is usually seen on the right side.