LEARNING TOPIC
Physiology of normal pregnancy

  updated 13 May 1999 

Keywords
  • human placental lactogen
  • human chorionic gonadotrophin
  • progesterone
  • weight gain
  • intermediary metabolism
  • cardiovascular system
  • respiratory system
  • renal tract
  • gastrointestinal tract
  • genital tract
   

Multiple changes occur in pregnancy to maternal anatomy, physiology, biochemistry and psychology. The main reasons for the changes are 1) to the nurture the fetus in an optimal environment, 2) to protect the mother from the risks imposed by pregnancy, 3) to prepare the mother for the delivery process, and 4) to prepare the mother for breastfeeding. The points to note are that the physiological changes I) occur early in pregnancy even though they may not be needed until the last trimester, II) exceed fetal needs, III) occur to a level that matches fetal size, and IV) all changes in the mother, except for stretch marks in the skin and the final stages of breast development that occur in early pregnancy, are completely reversible.

Most of the physiological changes in the mother are related to hormones associated with pregnancy. These hormones come from various sites. The most important are 1) Placental: human chorionic gonadotrophin (HCG), human placental lactogen (HPL), progesterone. 2) Feto placental: oestrogens, 3) Endometrial: prolactin, 4) Maternal: cortisol, renin/angiotensin/aldosterone.

HCG is a glycoprotein with both alpha and beta subunits, the beta subunit being specific to HCG and thus forms the basis of the commonly used pregnancy test. Concentrations rise in early pregnancy to very high levels but then fall again during the second trimester. Its actions are firstly to maintain the corpus luteum, in early pregnancy, secondly it acts as a thyrotrophin to increase thyroid hormone production and BMR in the mother, thirdly to induce fetal testosterone in the male fetus, and fourthly to regulate the fetal adrenal cortex. Human Placental Lactogen is a protein of 190 amino acids . It is similar in nature to human growth hormone. Its levels increase in relation to placental size. Its actions are to aid breast development for later breastfeeding, it antagonises the action of insulin on all tissues except the liver making the mother diabetogenic, it mobilises free fatty acids as the preferential form of nutrition for the mother, and has growth hormone like effects causing trophic changes in various organs of the body. Progesterone is initially secreted from the corpus luteum but as the placental develops is secreted from that source, and therefore concentrations relate to placental size. Its actions are thermogenic, it relaxes smooth muscle (this takes place in the uterus, uterers, eye, arterioles etc thus causing problems with vision and maintenance of blood pressure etc), it alters hypothalamic sensitivity to C02 causing mother to ventilate more rapidly and therefore blow off C02 causing a compensated respiratory alkalosis, it antagonises the action of aldosterone at the distal convoluted tubule, it antagonises the action of insulin at the periphery, it increases elastin levels in connective tissue this making joints more distensible, causes ductile growth in the breast and it increases the secretion of insulin, this latter factor causing a fall in the fasting level of blood glucose in pregnancy. Other hormones; oestrogens: increase breast development and increase water content of connective tissue; prolactin: controls amniotic fluid volume and aids breast secretory tissue development.

Specific changes in the mother are:

Weight Gain:

The average weight gain during pregnancy is 12.5 kg, approximately 80% of that weight gain occurring in the second half of pregnancy. The increase in weight is not only due to the presence of a fetus and placenta and amniotic fluid, but is also due to an increase in size of the uterus, an increase in blood volume, an increase in fat deposits, an increase in interstitial fluid, and an increase in breast tissue size. In order to maintain the increased nutritional requirements of pregnancy, a women needs to have an increased intake of energy at a level of approximately 300 kcal per day. Given that the levels of insulin are increased in the mother, and the effects of insulin at the periphery are antagonised during pregnancy, there is a marked change in the intermediary metabolism with an increase in free fatty acid utilisation. Glucose is therefore available for the fetus to grow, and readily crosses the placenta. The mobilisation of free fatty acids in pregnancy makes mothers susceptible to Ketone body production.

It should be noted that a women who is pregnant cannot cope with the glucose load as well as a non pregnant women due to the effects of the pregnancy hormones on insulin.

Cardiovascular system:

The vasodilatation due to progesterone increases regional blood flow to the kidney, skin, uterus, liver, gut, breast but not the brain. This vasodilatation is compensated by an increase in cardiac output by the mother which arises about 40% above the non pregnant level by 12 weeks of pregnancy. Similarly the plasma volume increases by between 30-50%, with the red cell mass increasing by 18-20%. The results of these changes mean that there is diminished cardiac reserve due to the increased cardiac output, the raised plasma volume causes a rise in the jugular venous pressure and pulmonary pressure, the rise in plasma volume out of relation to the rise in red cell mass causes a physiological anaemia in pregnancy, and mean blood pressure tends to fall particularly in the second trimester as the progesterone levels rise making the mother proned to fainting.

The Respiratory System:

The fetus utilises oxygen and produces carbon dioxide and non diffusible acids associated with metabolism. This factor, along with the resetting of the carbon dioxide receptors in the brain stem associated with progesterone, an increase in the intra-abdominal contents limiting the movement of the diaphragm, and a diminished defusing capacity in the lungs due to increased interstitial fluid and connective tissue, causes marked changes in the maternal respiratory system. In order to remove the carbon dioxide there is a rise in respiratory tidal volume by approximately 40%, however the respiratory rate does not change. This increase in tidal volume results in subjective dyspnoea. The increased problem tidal volume also decreases lung reserve which is important in women who have asthma. The respiratory alkalosis associated with the diminished carbon dioxide levels causes cramps and tetany, common problem in pregnant women. There is a small rise in the PO2 levels in the aorta however the major change within the blood gases is the fall in the carbon dioxide which is thought to be beneficial to off loading of carbon dioxide by the fetus.

The Renal System:

The increase non diffusible acids associated with the raised basal metabolic rate in pregnancy and the production of these acids by the fetus causes an increase load to the renal system. Renal vasodilatation results in an increase in blood flow to the kidneys of about 60% changing the glomerular filtration rate from 120 ml per minute in the non pregnant to 160 ml per minute in the pregnant. This increase in the glomerular filtration rate leads to an increasing number of amino acids and glucose being presented to the tubules after filtration at the nephron, and the excess load of these substances may lead to a degree of glycosuria or proteinuria being detected. The serum maternal plasma, urea and creatinine are lowered due to the increase glomerular filtration rate which is an advantage to the off loading the nitrogen waste from the fetus to the mother.

The GI Tract:

Progesterone relaxes smooth muscle in the GI tract and there is also a diminished buffering capacity of saliva due to the lowered serum bicarbonate associated with the levels of progesterone. The effects of these changes are to cause an increased rate of dental caries during pregnancy and also a problem with gastric emptying due to the smooth muscle relaxation. This diminished gastric emptying leads to increased stomach contents which leads to increased problems with oesophageal reflux as the uterus gets bigger and raises abdominal pressure. Gallstones in pregnancy are also increased due to the raised level of steroid excretion from the liver.

The Genital Tract:

During pregnancy, the uterus increases in weight by approximately 20 times due to hypertrophy of the myometrial muscle cell size. Progesterone diminishes electrical activity of the cells and therefore depresses formation of electrical connections between the cells causing the uterus to remain quiescent and compliable to the increasing size of the fetus, placenta, and the amniotic fluid. The cervix undergoes hypertrophy due to the increase in connective tissue collagen and this increase in collagen provides enough strength to ensure that the cervix remains closed until the effects of prostaglandin cause softening at the time of labour. The ovary provides the progesterone in early pregnancy to ensure that the conceptuous stays in utero. After 8 weeks however the placenta produces sufficient progesterone to keep the pregnancy in place and the ovary itself is in fact redundant after this time.

Recommended and Optional Readings and Resources

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Author/s:   Dr Henry Murray, Dept. of Obstetrics & Gynaecology, Nepean Hospital