Dr. ISHRAQ MOHAMMED

Early pregnancy In early pregnancy, the developing fetus, corpus luteum and placenta produce and release increasing quantities of hormones, growth factors and other substances in to maternal circulation which triggers a cascade of events. Changes in all body systems to prepare the mother to support fetal growth Following implantation, the maternal adaptation to pregnancy can be categorized based on following functions: 1. Increased availability of precursors for hormone production and fetal-placental metabolism. 2. Improved transport capacity. 3. Maternal-fetal exchange. 4. Removal of additional waste products.

Increased availability of metabolic substrates is achieved by increases in dietary intake. Transport capacity is enhanced by increases in cardiac output. The placenta regulate maternal-fetal exchange by weeks gestation. Disposal of waste product occurs through peripheral vasodilatation and by increases in ventilation and renal filtration.

Volume homeostasis Maternal blood volume expand during pregnancy to allow adequate perfusion of vital organs including the placenta and fetus, and to anticipate blood loss associated with delivery. The rapid expansion of blood volume begins at 6-8 weeks gestation and plateaus at weeks gestation. The most marked expansion occurs in extracellular fluid volume especially circulating plasma volume, this accounts for between 8 and 10 kg of average maternal weight gain during pregnancy.

The factors contributing to fluid retention are: 1. Sodium retention. 2. Resetting of osmostat. 3. Decrease thirst threshold. 4. Decrease plasma oncotic pressure. Consequences of fluid retention: 1. Decrease in haemoglobin concentration. 2. Decrease in haematocrit. 3. Decrease in serum albumin concentration. 4. Increasing in stroke volume. 5. Increasing in renal blood flow.

Blood Haematology Maternal Hb levels are decreases because of discrepancy between increases in plasma volume &the increases in erythrcyte mass. The mean Hb concentration falls from 13gm/dl in non-pregnant state to10,9gm/dl at 36 weeks of normal pregnancy. The haematocrit is also reduced 32-34per cent. Pregnancy without iron supplementation lead to depletion of iron stores. Renal clearance of folic acid increase leads to fall in plasma folate conc. However red cell folate conc. Do not fall to the same extent. Folate supplementation in women eating adequate diet & carrying a single fetus is not routinely indicated. Platelet count may be lower than the non-pregnant state due to increased aggregation. Erythrocyte sedimentation rate is inreased in pregnancy

Haemostasis &coagulation Pregnancy is a hypergoagulable state & return to normal around 4 weeks after delivery. Almost all procoagulant factor including factor 7,8,9,10&11& fibrinogen are increased during pregnancy Fibrinogen is increased by 50 per cent 300mg/dl to 450mg/dl in pregnancy Level of von Willebrand factor increase in pregnancy The increase in procoagulant, potential for vascular damage & increase venous stasis particularly in the lower extremities, explain why the incidence of venous thromboembolic complications is five times greater during pregnancy but this is to protect women from bleeding after delivery Activated protein c resistance is increased in pregnancy D-dimers increased in pregnancy

Biochemistry Plasma protein concentration particularly albumin, are decreased during normal pregnancy, which not only affects the plasma oncotic pressure, but also affects the peak plasma concentration of drugs that are highly protein bound. Serum creatinine, uric acid & urea concentration are reduced during normal pregnancy. Alkaline phosphatase levels increases thoughout pregnancy. In contrast SGOT & SGPT show lower level in uncomplicated pregnancy

The immune response Immunobiology of the maternal-fetal interaction: The presence of the fetus is analogous to the grafting of tissues or organs between two individuals of the same species who are genetically dissimilar. Proposed mechanisms for the success of the fetal allograft: 1- maternal/systemic: none (normal cell mediated immunity). 2-fetal: a-uterus & local lymphatic system: -uterus has been considered as privileged immunological site. -localized, non specific suppression induces tolerance & generate suppressor T cells. b-placenal: -separation of the maternal-fetal circulations, including tight local barriers. -lack of expression of class 2 HLA at the maternal-fetal interface. -limited immune response of cytotoxic T lymphocytes to trophoblasts. c-sytemic : unidentified humeral &cellular immunosuppressive elements.

The maternal brain & the senses Decline in memory in the third trimester, the underlying mechanisms are less clear. Proposed causes include lack of oestrogen or elevated level of oxytocin, which has an amnesic effect while progesterone has a sedative effect. Pregnant women appear to have greater tolerance for pain, which is biochemically mediated by increased serum level of B- endorphins THE SENSES Changes in perception of odours during pregnancy,olfactory sensitivity & odour thresholds are significantly decreased during the third trimester. Corneal sensitivity decreases inmost pregnant women & this can be related to an increase in corneal thickness caused by oedema & a decrease in tear production occurs in around 80 per cent of pregnant women.

Respiratory tract Airway: the neck, oropharyngeal tissues, breast & chest wall are all affected by weight gain, breast engorgement & air way edema, can compromise the airway leading to difficulty with visualization of the larynx during tracheal intubation. Ventilation: this begins to increase significantly at around 8 weeks gestation in response to progesterone sensitization of the respiratory centre to CO2.the diaphragm is elevated 4cm by the enlarging uterus& the lower chest circumference expand by 5cm. Increase minute ventilation Increase tidal volume Decrease residual volume Decreased functional residual capacity Vital capacity unchanged or slightly increased

Oxygenation: during pregnancy there is an increase in 2,3-diphosphoglycerate concentration within maternal erythrocytes. This lead increase availability of oxygen within the tissues(shifts the oxygen-hemoglobin dissociation curve to the right). Decreased Pco2 Increased pO2 PH alters little Increased bicarbonate excretion

Cardiovascular system Sign & symptoms of pregnancy mimics those of heart disease such as breathlessness, edema in the extremities, palpitation are common & usually represent sinus tachycardia, which is normal in pregnancy. In normal pregnancy, cardiac output increases as early as5 weeks gestations Non pregnant adult female4.5L/min 20weeks pregnant6.3L/min 40per cent rise Early labour17 per cent rise 7.3 Active labor 7.7 L/min 2 nd stage of labor 8.4 Most increase in cardiac output is contributed to raise of stroke volume Decreases in diastolic blood pressure are more marked than the decrease in systolic pressure lead to increase in pulse pressure. Later, diastolic blood pressure increases to level that are at least equivalent to those found in the non-pregnant state. The best measurement are obtained when the fifth Korotkoff sound is used

A 70 per cent reduction in peripheral vascular resistance has been demonstrated by 8 weeks gestation due to alteration in the production vasoconstrictor& vasodilator agent that peripheral arterial tone. 1 st heart sound is loud, wide splitting of the 2 nd heart sound, 3 rd heart sound is audible in 84 per cent of the pregnant women by 20 weeks gestation, an ejection systolic murmur can be heard in 96 per cent of normal pregnant women, diastolic murmur occur transiently in only 20 per cent of pregnant women &10 per cent develop continuous murmur due to increased mammary blood flow.

Gastrointestinal changes Oral: pregnancy gingivitis, edema, hyperplasia & increased bleeding of gingival tissue & dental caries &increase tooth mobility. Gut: the uterus displace the stomach & intestine upwards, increase incidence of reflux oesophagitis & heartburn, delayed gastric emptying. Liver: physical finding such as telangiectasia & palmer erythema, otherwise suggestive of liver disease in non- pregnant women, appear in up to 60er cent of normal pregnancies because of the hyperoestrogenic state of pregnancy. Absolute hepatic blood flow remain largely unaltered & hepatic function remain normal.

The kidney & urinary tract Increased kidney size(1cm) Dilatation of renal pelvis & ureters Increase blood flow(60-75per cent) Increase glomerular filtration (50per cent) Increase renal plasma flow(50-80per cent) Increase clearance of most substance Decreased plasma creatinine, urea& urate Glycosuria is normal

Reproductive organ Uterus: uterine blood flow increases 40- folds(700ml/minute at term) High levels of maternal oestradiol & progesterone induce hyperplasia &hypertrophy of the myometrium increasing the weight of the uterus from 50-60gm prior to pregnancy to 1000gm by term. By the third trimester, the uterus is described in lower & upper segments. In addition to changes in the size &number of myometrial cells, intercellular gab junction facilitating the spread of membrane depolarization & subsequent myometrial contraction. These are apparent initially as Braxton Hicks, painless contractions that are notice in the 2 nd half of pregnancy.

cervix: looks bluer during pregnancy, swollen &softer under the influence of progesterone & oestradiol. Vaginal epithelium becomes more vascular during pregnancy, & there is increased desquamation resulting in increased vaginal discharge. This discharge has a more acid pH & may protect against ascending infection Breast & lactation: the number of glandular duct is increased by oesrtogen, while progesterone & human placental lactogen increase the number of gland alveoli.

Endocrinology Hormones produced within pregnant uterus 1. Pregnancy specific: hCG& hPL 2. Hypothalamus: GnRH & CRH 3. Pituitary: prolactin, hGH, ACTH 4. Steroids: oestradiol, progesterone 5. Other peptides: insuline like growth factor, parathyroid hormone related peptide, renin & angiotensin 2

Pituitary gland Enlarged, concentration of prolactin 15 fold increase which is necessary for initiation of lactation, it also may play a role in the regulation of insulin secretion. Human growth hormone production by the anterior pituitary gland is suppressed during pregnancy & human placental lactogen is involved in suppressing its release. Thyroid function : maternal TSH production is suppressed during the first trimester but return to normal after this. Thyroid binding globulin increases in the first 2 weeks of pregnancy & reaches a plateau by 20 weeks. Increase renal loss of iodide which result in enlargement of the thyroid gland during pregnancy.

Uterus & placenta HCG produced by the trophoblast cells, the B-subunit is pregnancy specific & used as a sensitive pregnancy test, this hormone has a major role during early pregnancy in maintaining the function of corpus luteum, which produces progesterone. Sex steroid hormones are produced in large quantities by the placenta & fetus. Oestrogen encourages cellular hypertrophy of the myometrium while progesterone discourages contraction &, together with prolactin, on the tissues of breast.

corticosteroids A progressive increase in maternal circulating concentrations of cortisol throughout normal pregnancy has been notice as early as 11weeks & reaches 2-3fold higher concentration than in the non-pregnant. Much of cortisol is bound to cortisol-binding globulin, which doubles in concentration during pregnancy, but there is also a slight increase in unbound cortisol. Aldosterone increase ten-fold in pregnancy. The increased production of angiotensins is the result of increase production of the enzyme renin & its substrate angiotensinogen.

Corticotrophin-releasing hormone (CRH) is produced by the placenta in the second half of pregnancy, which stimulate the fetal adrenal to synthesize & release dihydroepiandrosterone, which the placenta then converts to oestrogen. It also stimulate the fetal adrenal gland to synthesize & release cortisol. CRH peak level 48hours before delivery. The placental regulation of its own metabolism through effect on the fetus, with subsequent effects on maternal uterine physiology, & possibly the onset of labor, has been called the placental clock theory.

Metabolism Energy requirements & weight gain Carbohydrate metabolism Lipid metabolism Calcium meabolism Skin changes: Hyperpigmentation Striae gravidarum Hirsuitism Increase sebaceous gland activity.

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