GENITAL TRACT
Uterus
• The weight, internal volume and dimensions of the uterus increase compared to the pre-pregnancy period. This uterine growth occurs due to hypertrophy and stretching of muscle cells, and new myocyte formation is limited.
• 6-8 weeks of pregnancy. The fundus is softer than the cervix and the isthmus is compressible and excessively softened (Hegar sign).
• After the 12th week, the uterus enlarges to protrude beyond the pelvis, and the uterus is slightly turned to the right due to the presence of the sigmoid colon on the left. uterine pregnancy It reaches the level of the navel in the 20th week, and reaches the xiphoid in the 36th week. When engaged, it slowly descends.
• In the case of a term pregnant woman lying on her back, venous return to the heart is reduced due to the enlarged uterus's compression on the aorta and inferior vena cava. When a term pregnant woman needs to lie on her back, turning her to her left by 15-30 degrees will prevent supine hypotension.
• Due to the effect of estrogen, progesterone, relaxin and some adipocytokines (Chimerin, visfatin, leptin, resistin, adiponectin) during pregnancy, uteroplacental blood flow gradually increases throughout pregnancy and is 450-650 ml/min at term. . During contractions, the flow is markedly reduced.
In normal pregnancy, there is resistance to the vasopressor effects of angiotensin II and norepinephrine.
cervix
• Cyanosis and softening of the cervix are observed due to increased vascularity, diffuse edema, and hypertrophy and hyperplasia of the cervical glands during pregnancy (Godell's sign). Eversion occurs due to columnar cell metaplasia.
• The cervical canal is covered with a mucus plaque (marker) and this plaque is expelled at the beginning of labor. If the cervical mucus is dried and examined, a fern appearance is not observed due to poor crystallization.
vagina
• Increased vascularization and hyperemia are seen in the vagina, and accordingly the vagina turns purple (Chadwick's sign). Mucosal thickness increases, loosening of connective tissue and hypertrophy of smooth muscle cells occur.
• Vaginal pH is between 3.5-6.0.
ovary
• Ovulation stops during pregnancy in the ovary.
• While the corpus luteum is the main source of progesterone until the sixth and seventh weeks of pregnancy, progesterone secretion decreases after this week. The increase in the level of relaxin in the early weeks of gestation is due to the secretion from the corpus luteum.
SKIN
Hyperpigmentation
• There is increased pigmentation in the areola and genital area. This increase in pigmentation is due to the increase in melanocyte stimulating hormone. Linea alba hyperpigmentation is called linea nigra.
Chloasma (Melasma - Pregnancy Mask)
• They are macular hyperpigmentations on the forehead, cheeks and nasal root. It regresses after birth, but it can also be permanent.
Telangiectasia (Spider Angioma) and Palmar Erythema,
• They occur due to increased estrogen, but disappear in the postpartum period.
Striae Gravidarum
• It is due to collagen breakage that occurs as a result of excessive stretching of the skin. They are red, slightly sunken irregular lines that can be seen on the skin of the abdomen, chest, thighs and buttocks. Once formed, it cannot be recycled.
Hair Changes
• While the anagen phase (growth) is prolonged during pregnancy, the postpartum telogen ratio (resting) increases. Although not exaggerated in most pregnant women, excessive hair loss in the puerperal period is called telogen effluvium.
BREAST
• Breast tenderness and pain are common in the early weeks of pregnancy. From the second month, the breast volume increases and the veins begin to appear on the skin. Nipple enlarged, pigmented and erect! becomes. Colostrum may come after the first months. Hypertrophic sebaceous glands appear in the areola (Montgomery glands). Striae may occur as in the abdomen.
Prolactin plays an important role in lactation and increases throughout pregnancy. However, lactation is constantly suppressed by estrogen, progesterone and hPL so that it does not start before birth. Lactation begins with the sudden drop in the levels of these hormones after birth.
Hormones related to breast development and lactation
Mammogenesis (Breast development)
estrogen
progesterone
prolactin
Growth hormone
epidermal growth factor
Glucocorticoids
insulin
Lactogenesis (Start of milk secretion)
Estrogen reduction
Decreased progesterone
hPL reduction
prolactin
Glucocorticoids
insulin
Galactogenesis (continuation of milk secretion)
Absorption (Oxytocin + Prolactin)
low estrogen
low progesterone
insulin
Growth hormone
T4 and parathyroid hormone
Glucocorticoids
METABOLIC CHANGES
Metabolic Rate
• In the third trimester of pregnancy, the basal metabolic rate increases by approximately 20%.
Weight Gain
• The most striking physiological change in pregnancy is the recommended weight gain of 11.5-16 kg.
Distribution of weight gain in a term pregnancy
Fetus------------------------------------------------ ------------------------------------------ 3400 g
Placenta------------------------------------------------- -----------------------► 650g
amniotic fluid------------------------------------------------ ----------------► 800g
Uterus------------------------------------------------- --------------------------► 970 g
Blood volume increase------------------------------------------------ -----------► 1450 g
Maternal fat deposition------------------------------------------------ --► 3345 g
Extravascular fluid------------------------------------------------ -----► 1480 g
Breast tissue------------------------------------------------ ---------------► 405g
Total------------------------------------------12.5 kg
Protein Metabolism
• Total protein, albumin and colloid pressure decrease during pregnancy. In contrast, the total globulin concentration increases.
• Binding proteins, transferrin, pregnancy-specific proteins, IgM and IgD increase, while IgG decreases.
• The concentration of most amino acids {ornithine, glycine, taurine, proline) is reduced in maternal plasma.
Carbohydrate Metabolism
• Pregnancy is characterized by mild fasting hypoglycemia, postprandial hyperglycemia and hyperinsulinemia. Since the resistance of peripheral insulin increases during pregnancy, latent diabetes becomes evident or worsens if diabetes is present.
• A number of endocrine and inflammatory factors are responsible for the increase in insulin resistance and decrease in insulin sensitivity during pregnancy. These include pregnancy-related hormones {human placental lactogen, progesterone, placental-derived growth factor, prolactin and cortisol}, cytokines {TNF}, and central adipose tissue-derived hormones {leptin} and hormones interacting with prolactin.
• While glomerular filtration of glucose increases during pregnancy, tubular reabsorption decreases minimally. Therefore, physiological glucosuria is seen in half of the pregnant women (150 mg/dl).
Lipid Metabolism
• All lipids increase during pregnancy {triglyceride, T.cholesterol, VLDL, HDL, LDL, apolipoproteins, phospholipids, free fatty acids}. The main mechanism responsible for these changes is increased lipolytic activity and decreased lipoprotein lipase activity in adipose tissue.
• Leptin; It is associated with fetal birth weight because fetal organs have a role in development. Low leptin levels are associated with IUGR. It is secreted mainly from adipose tissue and partially by the placenta. Therefore, there is a significant correlation between placental weight and leptin level. Maternal serum leptin levels increase during pregnancy. Leptin level peaks especially in the second trimester and then plateaus and maintains this level until term. In addition, abnormal leptin elevations have been associated with preeclampsia and gestational diabetes.
• Ghrelin; It is secreted from the placenta and has a role in fetal development.
Water and Mineral Metabolism
• From the early period of pregnancy, tubular reabsorption increases and water retention occurs in the body. As a result, there is an increase of approximately 6.5 liters of extracellular fluid in pregnant women.
Edema is normal in pregnant women, it does not show any pathology
• Glomerular filtration of sodium (Na) and potassium (K) increases during pregnancy, and 1,000 mEq Na and 300 mEq K are uptake during pregnancy. However, Na and K levels are relatively low due to the increase in plasma. (0.5 mEq/L drops). Since the tubular resorption of these electrolytes has increased, their urinary excretion does not change.
Serum osmolarity decreases in pregnant women.
• While the total calcium concentration decreases during pregnancy, the ionized calcium level does not change. On the other hand, the level of both the total and ionized form of magnesium decreases significantly in pregnant women. The phosphate level in the serum does not change.
Folate Metabolism
• The need for folic acid increases during pregnancy and this need becomes 400-800 µg/day.
• Folic acid needs increase in cases such as multiple pregnancy, hemolytic anemia, Crohn's disease, alcoholism and inflammatory skin diseases, children with NTD and family history of congenital heart disease.
Disorders that can be seen in folic acid deficiency
1. Megaloblastic anemia
2. Neural tube defect
3. Preeclampsia
4. Ablation placenta
5. Fetal cardiac anomaly
vitamins
• Diet is sufficient for many vitamins.
• Vit B12 decreases during pregnancy and this decrease is due to the decrease in transcobalamin. Vit 86 support is useless; however, it is beneficial to use it together with doxylamine in the treatment of nausea and vomiting. Vitamin D deficiency is common during pregnancy and 15 ug/day (600 IU) vitamin D intake is sufficient during pregnancy and lactation.
HEMATOLOGICAL CHANGES
Blood Volume
• The blood volume increases by approximately 1600-1700 ml. The increase in blood volume is due to an increase in both plasma and erythrocyte levels, but most of the increase occurs in plasma (1200 ml). Since the erythrocyte volume increases by only 450 ml, there is a physiological anemia with dilutional effect. Therefore, hemoglobin concentration and hematocrit decrease slowly throughout pregnancy. Erythropoietin levels increase during pregnancy and peak in the third trimester. Accordingly, there is mild erythroid hyperplasia in the bone marrow during pregnancy and the reticulocyte count increases slightly during normal pregnancy.
• There is a picture of leukocytosis in pregnancy (15,000/ul). Especially in travay, it can rise up to 25,000.
• Platelet count also decreases during pregnancy.
changes in blood cell content during pregnancy
Neutrophil ► Increases
Erythrocyte ► Increases
Erythrocyte fragility ► Increases
Sedimentation ► Increases
Leukocytes ► Increases
Cover. melt. Volume ► Slightly increases
Lymphocyte ► Unchanged
Cover. melt. Hgb. Conc ► Invariant
Basophil ► Decreases
Hemoglobin ► Decreases
Hematocrit ► Azahr
Platelets ► Decreases
Iron Metabolism
• The need for iron increases during pregnancy and usually this open store cannot be met by iron. From early pregnancy periods, hepcidin levels decrease and accordingly, iron absorption in the intestines increases (up to 40%). However, iron supplementation may be required as the daily requirement is 6-7 mg/day.
• Serum iron and ferritin levels decrease during pregnancy. However, a serum ferritin level of <10-15 mg/L during pregnancy makes the diagnosis of iron deficiency anemia.
• There is no need for iron support for the first 4 months in pregnant women who do not have anemia. The reason for Hb concentration below 11 g/dl in the second half of pregnancy is iron deficiency rather than hypervolemia. Pregnant women should be given 30 mg of elemental iron daily as a supplement.
Coagulation System
• Fibrinogen (factor I) increases. This increase is the most important reason for the increase in sedimentation during pregnancy.
• Plasminogen activator inhibitor 1-2 (PAI-1,2) levels increase during pregnancy and accordingly, the efficiency of tissue plasminogen activator (tPA) decreases. As a result of all these, fibrinolytic activity is insufficient during pregnancy. Therefore, there is hypercoagulability in pregnant women and the risk of thromboembolism in pregnant women is 5 times higher than in normal women.
Coagulation changes in pregnant women
F 1 (Fibrinogen) F 5, F 7, F 8, F9, F10, F12 ---increases
PA1-1 , 2 ► Increases
Plasminogen ► Increases
Thrombin time ► Increases
aPC resistance ► Increases
Activated PTT ► Unchanged
F 11 (prothrombin) ► Does not change
Antithrombin ► Unchanged
F XI, XIl1 ► Decreases
tPA activity ► Decreases
Protein C and S ► Azahr
aPC level------decreases
CARDIOVASCULAR SYSTEM
Heart
• In the last trimester, with the rise of the diaphragm, the heart is pushed upwards, rotates forward and the left margin is displaced laterally. Due to this displacement, the most common change in the ECG is mild left axis deviation.
• Significant changes occur in heart sounds:
► The first heart sound is markedly doubled and its volume increases.
► There is no change in the aortic and pulmonary elements of the second heart sound.
► The third heart sound becomes clear and easily audible.
► Systolic murmur is normal up to 3rd degree.
► Diastolic murmur is not normal and should be investigated
• Cardiac output increases and becomes 6 L/min. The output, which increases by 30-50% during pregnancy, increases the most within 10-30 minutes following birth.
• The increase in heart rate occurs with the inotropic effect of the increased estrogen of pregnancy. If the heart rate rises above 100 beats/min, it should be investigated.
Hemodynamic Functions
Status of hemodynamic parameters in term pregnant (compared to puerperium and non-pregnant)
Heart rate ► Increases
Cardiac output ► Increases
Mean arterial pressure ► Does not change
Pulmonary capillary wedge pressure ► Does not change
Central venous pressure ► Does not change
Left ventricular power index ► Unchanged
Pulmonary vascular resistance ► Decreases
Systemic vascular resistance ► Decreases
Colloid oncotic pressure ► Decreases
Blood pressure
• There is a slight decrease in blood pressure in 24-26 weeks of pregnancy and this decrease is more evident in diastolic pressure. Diastolic pressure decreases slightly in the first two trimesters; however, it returns to its normal level in the pre-pregnancy period at term
• Renin, angiotensin II and aldosterone levels increase.
• PgE2 and Pgl2 increase.
• Atrial natriuretic peptide and brain natriuretic peptide levels do not change.
THE RESPIRATORY SYSTEM
• The increase in basal oxygen consumption during pregnancy, excessive increase in progesterone (resistance in the pulmonary vessels decreases), and the ribs opening outward and the diaphragm rising up to 4 cm create some differences in respiratory functions and capacities during pregnancy.
Changes in the respiratory system
Increases:
1. Tidal volume 150- 200 mL
2. Inspiratory capacity increases by 5-10% (200- 250 mL)
3. Minute ventilatory volume increases by 40% (3,000 mL/min)
4. Minute oxygen uptake
5. Peak expiratory flow rate
6. Oxygen consumption
invariants
1. Lung compliance
2. Vital capacity
3. Respiration rate
4. Inspiratory reserve volume
Descendants
1. Total lung capacity is reduced by 5% (200 ml)
2. Functional residual capacity decreases by 20-30% (400-700 mL) -96)
3. Residual volume decreases by 20-25% (200-400 mL)
4. Expiratory reserve volume decreases by 15-20% (200-300 mL)
• Arterial pCO2 decreases slightly as tidal volume increases. Mild compensated respiratory alkalosis (pH 7.45) occurs due to hyperventilation during pregnancy. In contrast, HCO3 decreases compensatory (20-22 mEg/L).
• This pH increase shifts the oxygen dissociation curve to the left, increasing maternal hemoglobin's affinity for oxygen, thereby reducing the oxygen-freeing capacity of maternal blood. The decrease in pCO2, which develops as a result of maternal hyperventilation, facilitates the passage of CO2 from the fetus to the mother, while at the same time increasing the oxygen transmission to the fetus.
URINARY SYSTEM
• There is a slight increase in kidney size and approximately 30% volume increase in both kidneys during pregnancy. Hydroureter and hydronephrosis can often be seen on the right side due to compression and dextrorotation of the pregnant uterus.
• Asymptomatic bacteriuria occurs in 5% of pregnant women, of which 25-30% causes pyelonephritis. The ureters dilate and the slowing of the urine flow increases the susceptibility to infection.
• In addition to physiological glucosuria during pregnancy, physiological proteinuria is also seen due to the decrease in hyperfiltration and tubular reabsorption, and it is more prominent especially in the second half of pregnancy. The upper limit for physiological proteinuria in pregnancy is 300 mg/day. Hypercalciuria is also observed during pregnancy.
• Daily urine volume increases by 25%, nocturia and frequent urination can be seen. While glomerular filtration rate (GFR) increased by 50% , creatinine clearance Increases by 30%. The serum creatinine level decreases by 25% and at values of 0.9 mg/dl and above, the patient should be investigated for renal pathology. Urea level (25%) and uric acid level also decrease.
In preeclampsia, serum uric acid level is increased due to decreased GFR. The first biochemical marker of preeclampsia may be an increase in uric acid levels.
Relaxin is involved in an increase in GFR and an increase in renal blood flow.
GASTROINTESTINAL SYSTEM
• Nausea and vomiting (emesis gravidarum) is seen in 70% of pregnant women, usually peaks at the 10th week and lasts until the 16th week.
• With the effect of progesterone, relaxation of the smooth muscles of the gastrointestinal tract and, as a result, decrease in intestinal motility, reflux esophagitis (pyrosis) due to relaxation of the lower esophageal sphincter are observed.
• During pregnancy, gastric acid secretion is decreased but mucus secretion is considerably increased, so active peptic ulcer is almost never seen in pregnant women .
• An increase in gastric volume is observed in pregnant women due to increased gastric secretion. There is no slowdown in gastric emptying rate during pregnancy; however, gastric emptying rate slows down when labor begins.
• Relaxation in the colon leads to an increase in water and salt absorption and, as a result, constipation. Hemorrhoids are common in pregnant women due to compression and constipation.
• Gallstone formation becomes easier during pregnancy. The reason for this is the decreased contractility of the gallbladder that occurs with progesterone activity, the condensation of bile and the increase in the residual volume of the gallbladder. Cholesterol stones are the most common gallstones in pregnant women.
• Liver function tests (AST, ALT, GGT) and bilirubin levels are slightly decreased. Serum alkaline phosphatase increases 2-fold (placental synthesis increased). Bromsulfophthalein (BSP) clearance is reduced. Spleen size increases approximately 70% during pregnancy, but hepatomegaly is a potentially pathological finding (A-18).
ENDOCRINE SYSTEM
• The pituitary gland is the most enlarged endocrine gland (135%). While an increase in lactotroph cells and a decrease in gonadotroph and somatotroph cells are observed, the amount of corticotropic and thyrotropic cells does not change. Prolactin levels in pregnant women can increase up to 10 times normal. However, the incidence of prolactinoma does not increase during pregnancy. Even in women who are breastfeeding after giving birth, prolactin levels decrease. However, there are pulsatile increases in secretion in response to breastfeeding in early lactation periods.
• Thyroid gland enlarges anatomically, glandular hyperplasia and vascularity increase. With the effect of high estrogen, thyroxine binding globulin (TBG) increases. Total thyroxine (T4) level increases; however, there is a slight increase in the free thyroxine (T4) level due to the increase in hCG, and then it goes down to normal. Total triiodothyronine (T3) increases; however, there is no significant change in free triiodothyronine (T3) level. Resin T3 uptake (uptake} decreases. TRH level does not change during pregnancy. However, TRH may cross the placenta and stimulate thyrotropin release from fetal pituitary. Although thyrotropin (TSH) level is slightly suppressed during pregnancy, serum level is within normal limits in non-pregnant women.
• Iodine requirement increases in normal pregnancies due to the increase in maternal and fetal thyroid hormone production and renal excretion of iodine during pregnancy.
• The plasma concentration of parathyroid hormone decreases during the first trimester and then increases progressively until the end of pregnancy.
• Serum 1,25-dihydroxyvitamin D3 level in pregnant women increases due to placental PTH or PTH-related protein (PTH-rP), and accordingly, calcium absorption in the gastrointestinal tract increases, especially in the third trimester.
• While the corticotropin (ACTH) level is low in the early weeks of pregnancy; In the following weeks, both ACTH and free cortisol levels increase. Serum total cortisol level increases in pregnant women; however, most of it is bound to increased transcortin (cortisol binding globulin). Although the production of adrenal cortisol does not increase, the reason for the increase in cortisol level is that the metabolic clearance of cortisol is reduced by half.
• Aldosterone level increases during pregnancy and has a role in determining the trophoblast development and placental diameter. Deoxycorticosterone level also increases 15 times during pregnancy. The level of antiduretic hormone (vasopressin) does not change during pregnancy.
• Androstenedione and testosterone levels increase in maternal serum; however, since almost all of them are converted to estrogen in trophoblasts, there are no fetal side effects. DHEA-S levels are decreased in maternal serum and urine.
IMMUNOLOGICAL SYSTEM
• In order not to reject the semiallogeneic fetal graft during pregnancy, some adaptations occur in the humoral and cellular immune system and immune silence is ensured.
• Th2-mediated immune system becomes dominant to Th1-mediated immune system. Suppression of Th1-dependent immunity plays an important role in maintaining pregnancy. This is the main reason why Th1 activity-dependent autoimmune diseases (rheumatoid arthritis, multiple sclerosis, Hashimoto's thyroiditis) go into remission during pregnancy.
• While T lymphocyte counts increase during pregnancy, B lymphocyte count and CD4/CD8 T lymphocyte ratio do not change.
• C-reactive protein level, which is an inflammation marker, increased in pregnant women and continues to increase in labor. Another marker, the erythrocyte sedimentation rate, is also increased during pregnancy (due to increased plasma globulin and fibrinogen). In the second and third trimesters of pregnancy, complement factors C3 and C4 are very high. Procalcitonin levels also increase at the end of the third trimester and in the first few days postpartum.
MUSCLE AND SKELETON SYSTEM
• Normal pregnancy is characterized by progressive lordosis and the center of gravity shifts forward.
• Sacroiliac, sacrococcygeal and pubic joint mobility also increases.
CENTRAL NERVOUS SYSTEM and EYE
• During pregnancy, a decrease is observed in middle and posterior cerebral artery blood flow, especially in the late stages of pregnancy, and mild concentration, attention and memory problems are observed in most pregnancies.
• Intraocular pressure decreases due to the increase in the flow of vitreous fluid. While corneal thickness increases slightly, corneal sensitivity decreases. Brown/red opacities (Krukenberg spindles) may be observed on the posterior surface of the cornea; however, visual functions are not affected during pregnancy.
• Pregnancy causes an increase in sleep disorders and changes in sleep patterns. In the third trimester, Stage 1 non-REM sleep increases, while total sleep time, Stage 3 and 4 non-REM sleep and REM sleep decrease.