PHYSIOLOGICAL CHANGES IN PREGNANCY

Reproductive organs

A) Uterus:

 The muscular organ holding the fetus during pregnancy, nourishment of the fetus through the placenta. It is divided into the body (Corpus, and fundus)and the cervix.

During pregnancy, the uterus increases in weight from 60 to 1000g. In size, it changes from 6.5 to 32 cm. In a non pregnant state, the uterus is situated in the pelvic cavity. During pregnancy, it expands into the abdominal cavity. In addition to the growing foetus, uterine expansion is caused by an increase in connective tissue and in the size and number of blood vessels supplying the uterus

 

Ligamentous supports:

1) Round ligaments are fibrous cords attaching to the uterus and libia  majora  During pregnancy, they become elongated and hypertrophied. They supportthe uterus in its move from the pelvic cavity into the abdominal cavity.

 

2) Broad ligaments are large folds of peritoneum separating the pelvis into the anterior and posterior divisions. The lower portion of the ligament is known asthe cardinal ligaments, it attaches the lateral aspect of the uterus to the supravaginal area of the cervix.

 

3) Utero sacral ligaments attach the sacrum to the posterior aspect of the cervix to support the cervix.

Cervix: 

The portion of the uterus connecting the body of the uterus and the vagina.

1) The internal os joins the body of the uterus with the cervix.

2) The external os opens into the vagina.

3) During pregnancy, the cervix is closed. A mucus plug forms over the cervix , providing a protective barrier between the vagina and the uterine contents.

4) During labour and delivery, the cervix shortens (or effaces) and widens (or dilates), effectively disappearing. A 10 cm opening is left between the uterus and the vagina to allow for passage of the foetus into the birth canal.

5) If the cervix begins dilating prematurely, it is sometimes stitched together during the second trimester, until the foetus in mature. This procedure is known as a cerclage.

B) Ovaries:

 The organs storing ova. Through hormonal influence , one ovum is developed per month. It then travels into the fallopian tube and has the potential to be fertilized. One ovary is located on either side of the uterus, encased in the posterior aspect of the broad ligaments.

C) Fallopian tubes:

   The ducts bringing mature ova from the ovaries to the uterus via peristaltic action.

a) The fallopian tubes connect the uterine cavity to the abdominal cavity, near to the ovary. The opening at the abdominal site is lined with cilia to promote the peristalsis necessary to convey the ovum into the tube.

b) They are situated in the superior margin of the broad ligaments

D) Vagina:

The connecting passage between the uterus and the perineum, serving as the birth canal

a) The anterior borders include the bladder and the urethra.

b) Laterally, the ureters and broad and round ligaments lie.

c) Posteriorly, the peritoneum and the rectovaginal fascia.

Skin and hair system

Cutaneous system

    Due to overstretching of the skin, the elastic fiber may rupture together with small blood vessels and so red streaks appear; known as striae gravida rum. They  are usually more marked below the umbilicus, on the breasts and may appear on the buttocks and thighs. In some women they are not marked or even don't

   appear during pregnancy. After labour, the red striae become pale silvery white due to fibrosis and are known as (striae albicantes).

Linea nigra

Pigmentation: It is due to suprarenal changes, it usually begins to appear after the 4th month. The pigmentation may appear anywhere but the commonest sites are:

1. Linea nigra: which is a line of pigmentation between the umbilicus and the symphysis pubis.

2. Increased pigmentation of the nipple as primary areola and appearance of the secondary areola.

3. Stria gravidarum stretch marks of pregnancy appearance of reddish lines in the abdomen and thigh. 

4. Cloasma gravidarum (Butterfly pigmentation) or mask face of pregnancy which is butterfly pigmentation of the forehead, nose, upper lip and the adjoining parts of the checks. This pigmentation may persist but the cloasma gravidarum usually disappears.

5. Falling of hairs and brittleness of nails may occur during pregnancy.

6. vascular  spider  Minute, red elevations on the skin common on the face, neck, upper chest,   and arms, with radicles branching out  from a central lesion. The condition is often  designated as nevus,angioma, or telangiectasis. It is due to increase estrogen hormone. 

7. Palmar erythema   The two conditions are of no clinical significance and disappear in most women shortly after pregnancy(estrogen).

Hair growth:

The cycle of hair growth is altered in pregnancy, with a greater proportion (95% vs 85%) of hairs in the actively growing phase. As a result, there are many over-aged hairs at the end of pregnancy, which fall out and lead to the common symptom of hair coming out ‘in handfuls’ postnatally. This change is temporary.

Dental and Buccal mucosa:

Gums may become hyperemic & soft during pregnancy and may bleed if mildly traumatized as with a toothbrush.

Epulis of pregnancy (a focal highly vascular swelling of the gum develops occasionally & regresses spontaneously after delivery.

Most evidence indicates that pregnancy doesn't incite tooth decay.

Gastrointestinal 

Pyrosis (heartburn) is common &is caused by reflux of acidic secretions into lower esophagus & decreased tone of sphincter action that mediated by progesterone. Intraesophageal pressure is lower & intragastric pressure is higher in pregnant women.

               

There is a general reduction in gut motility and a slowing of transit times. This may benefit the fetus by increasing the absorption of certain nutrients. Delayed gastric emptying and gastric relaxation are a feature of pregnancy, especially with highly osmotic foods (e.g. glucose) and are particularly marked in labour. 

Nausea and vomiting are common in early pregnancy. It is not clear whether they are caused by rising human chorionic gonadotrophin (hCG) or oestrogen levels or some other factor. 

Most pregnant women report increased appetite and thirst, and many have cravings for, or aversions to, certain foods. A pica will indicate a graving to a non food objects.

Gastric acid secretion is reduced in pregnancy, which is presumably the reason why peptic ulcer disease commonly improves. In contrast, reflux oesophagitis is likely to be more severe, and results from a combination of reduced tone in the lower oesophageal sphincter and increased intra-abdominal pressure.

Many women report constipation in pregnancy and this is usually attributed to the relaxing effect of progesterone on gut smooth muscle. There is, however, little good evidence that constipation really is more common in pregnancy. If it occurs, it should be managed, as in the non-pregnant state, with increased dietary fibre and stool-bulking agents.

 

Rectal haemorrhoids probably result from a combination of increased straining and increased intra-abdominal pressure, and as part of the generalized vasodilatation mentioned above.

Hepatobiliary

No increase in size of the liver of pregnant woman. There is no distinct changes in liver morphology as evidenced by histological evaluation of postmortem liver biopsies by EM. Despite this, there is increase in diameter of portal vein &its blood flow. Liver function tests varies greatly during normal pregnancy.

Serum alkaline phosphatase almost doubles (heat stable placental alkaline phosphatase isozymes). Biochemical tests of liver function, however, lie within the normal range, with the exception of alkaline phosphatase levels, which are approximately doubled. Most of this increase comes from placental secretion of this enzyme, rather than from the liver. 

Serum concentration of albumin decreases. Decrease in albumin to globulin ratio occurs due to combined reduction in albumin concentration & slight increase in serum globulin levels.

Normal pregnancy is a mildly ‘cholestatic’ state. Oestrogen increases the serum cholesterol and this is translated into bile salt production, which saturates the bile. Since progesterone also reduces gall bladder emptying, pregnancy predisposes to gallstone formation. Progesterone impairs gallbladder contraction by inhibiting cholecystokinin-mediated smooth muscle stimulation, primary regulator of gallbladder contraction.

Pregnancy causes intrahepatic cholestasis & pruritus gravidarum from retained bile salts. Cholestasis of pregnancy is linked to high levels of estrogen which inhibit transductal transport of bile acids, also increased progesterone & genetic factors has been implicated in pathogenesis.

Respiratory system

 During pregnancy, the body is in a state of hyperventilation due to high level of progesterone.

a. Breathing becomes more costal than abdominal. Additionally, most women are mouth breathers during pregnancy.

b. Anatomically. the diaphragm is progressively elevated. Possibly because of expansion and elevation of the rib cage. Uterine pressure during the first and second trimesters does not appear to be a factor in this phenomenon.

Oxygen consumption is increased by around 15–20%.

Around 40% of the increased oxygen requirement is for the feto--placental unit.

Pregnant women hyperventilate, increasing minute ventilation (the amount of air breathed in and out of the lungs in 1 minute) by about 40% above the normal 7 L/min. This increase in ventilation is far greater than the increase in oxygen consumption, effectively providing a safety net. The increase is predominantly achieved by increasing tidal volume rather than respiratory rate via an increase in tidal volume alone, as the respiratory rate does not change during pregnancy.[ – in other words, the mother breathes more deeply. As a result, carbon dioxide levels in the blood decrease and the pH of the blood becomes more alkaline (i.e. the pH is higher and more basic).  Also, Maternal serum CO2 falls, favoring CO2 transfer from the fetus to the mother.

Tidal volume, minute ventilatory volume, and minute oxygen uptake increase significantly as pregnancy advances.

T V  increase  by about 40% lead to   MVV from 7.25 liters to 10.5 liters.

The functional residual capacity (FRC) and the residual volume of air are decreased due to the elevated diaphragm.

Lung compliance remains  unaffected.

Airway conductance is increased and total pulmonary resistance is reduced, possibly as a result of progesterone action. 

Fetal respiration

1. The high O2 affinity of fetal haemoglobin. The dissociation curve of fetal haemoglobin is shifted to the left so that at a given PO2, the percentage saturation is higher than for adult haemoglobin. More importantly, for the fetal interest, at a given level of oxygen transfer the PO2 will be lower.

2.The high fetal Hb (normal 140–200 g/L) also results in a lower PO2 for a given saturation.

3. Finally, the passage of CO2 from fetus to mother helps increase maternal oxygen dissociation and fetal association. This shift of the maternal oxygen dissociation curve to the right caused by CO2 accumulation is called the Bohr effect.

CardioVascular 

There is a decrease in peripheral vascular resistance due to dilatation of peripherl arterioles leading to decreased peripheral resistance and sensation of hotness helping also to get rid of increased temerature.

Cardiac output rises by about 40%, from around 3.5 L/min to 6 L/min. As both stroke volume and heart rate increase. 

COP =  SV  X HR.

This high blood flow maximizes PO2 on the maternal side of the placenta and maximizes oxygen transfer to the fetal circulation. 

The plasma volume expansion and increased cardiac output may also help heat loss by increasing blood flow through the skin, thus compensating for the increased metabolic rate of pregnancy. 

Peripheral vasodilatation causes a feeling of warmth.

Late in pregnancy, the mass of the uterus is liable to press on, and partially occlude, the inferior vena cava. This reduced venous return leads to a reduced cardiac output and may lead to hypotension, so-called ‘supine hypotension’.

Blood, plasma and extracellular fluid volume:

On average, the total red cell mass increases steadily throughout the pregnancy by 25%, from around 1300–1700 mL.

The circulating plasma volume, however, increases by 40%, from around 2600–3700 mL. Because the plasma volume increases proportionately, more than red cell mass, there is a dilutional drop in the haemoglobin concentration and in the haematocrit, such that a haemoglobin level of 105 g/Lwould be normal in a healthy pregnancy.

Plasma colloid osmotic pressure falls in pregnancy; as a result, fluid shifts into the extravascular compartment, causing oedema. Around 80% of pregnant women have some degree of dependent oedema.

Blood constituents and physiological anaemia:

Iron requirements are increased to meet the requirements of the larger red cell mass, developing fetus and the placenta, and the serum ferritin level therefore falls. The fetus gains iron from maternal serum by active transport across the placenta, mostly in weeks 36–40. In the absence of iron deficiency, routine supplementation is not recommended. Nevertheless, iron deficiency is not rare particularly if iron stores are low before pregnancy. 

Folate metabolism:

The daily folate requirement rises from 50 μg to 400–600 μg, and folate deficiency may occur. It is usually possible to meet this increased requirement through a normal diet, although intake in those with a poor diet is likely to be inadequate. Daily folic acid supplementation from before conception reduces the risk of neural tube defects.

Coagulation and fibrinolysis in pregnancy

Pregnancy is a hypercoagulable state, with an increase in procoagulants (particularly fibrinogen, but also platelets, factor VIII, von Willebrand factor) and a reduction in naturally occurring anticoagulants (e.g. protein S and antithrombin). Fibrinolysis is also increased, so there is an increased net turnover of coagulation factors.

Fibrinolytic activity returns to normal within 1 h of placental delivery, suggestive that inhibition of fibrinolysis is mediated by the placental unit.

The reason for this hypercoagulable state is presumably, from a developmental point of view, to minimize blood loss at delivery, but the disadvantage is the increased risk of thromboembolic disease

              Platelets aggregability and prostaglandins:

In normal pregnancy, there is increased biosynthesis of eicosanoids – particularly prostacyclin (PGI2), a vasodilator with platelet inhibitory properties, and thromboxane A2, a vasoconstrictor with a tendency to stimulate platelet aggregation. As both usually increase in proportion to each other, there is a net neutralization and homeostasis is maintained. This homeostasis is disrupted in pre-eclampsia because of a relative deficiency in prostacyclin owing to either a decrease in its synthesis and/or an increase in the production of thromboxane A2. This imbalance leads to vasoconstriction, hypertension, and platelet stimulation.

Urinary system

Striking anatomical changes are seen in the kidneys and ureters. This  is due to changes in pelvic anatomy and is a feature of  a 'normal' pregnancy. Frequency of micturation is a common symptom of early pregnancy due to compression by a gravid uterus in the pelvis. and again at term due to engagement of the presenting part.

A degree of hydronephrosis and hydroureter exists. loss of smooth muscle tone due to progesterone, aggravated by mechanical pressure from the uterus at the pelvic brim. These changes predispose to UTI.

Kidneys : Renal blood flow and glomerular filtration rate (GFR) increase by about 60% from early in the first trimester to around 4 weeks postpartum. This causes a fall in plasma creatinine from around 73–47 mmol/L and urea from 4.3 to around 3.1 mmol/L. It is important to be aware of this fact when assessing renal function, as values that would appear normal pre-pregnancy may in fact indicate impairment in the pregnancy state. The increased GFR is not matched by increased tubular reabsorption and there would therefore be a tendency to lose sodium. Glycosuria is common because the filtered load of glucose is greater than the tubular reabsorption capacity. 

Again dilatation of the renal pelvis and ureters are caused by both progesterone and local obstruction by the gravid uterus. It occurs from early in the first trimester and results in urinary stasis, which increases the likelihood of urinary tract infection; this may be further exacerbated by the presence of glycosuria.

Nutrition and metabolism in pregnancy

Maternal weight gain

There are no reliable data available for weight gain in   

the first 12 weeks of

pregnancy. But in normal pregnancy the average gain is   0.3 Kg/week up to 18

weeks, 0.45 Kg/week from 18-28 weeks and a slight reduction with a rate of 0.36-

0.41 Kg/week until term.

Failure to gain weight and sometimes slight weight loss may occur in the last 2

weeks. The average weight gain for primigravidae for the inhal pregnancy is 12.5

Kg. and is probably about 0.9 Kg. less for multigravidae. Acute excessive weight

gain is commonly associated with abnormal fluid retention.

Weight gain is produced by:

Fetus 3.63-3.88 Kg

Placenta 0.48-0.72 Kg

Amniotic fluid 0.72-0.97 Kg

Uterus and breasts 2.42-2.66 Kg

Blood and fluid 1.94-3.99 Kg

 9.70-14.55Kg  total=    Muscle and fat 0.48-2.91 kg

The developing fetus requires energy, largely provided by glucose, amino acids and fatty acids. These are mostly transported across the placental membrane by active processes. In later pregnancy, excessive glucose is converted into glycogen and fat, such that by term, 15% of the body weight is fat. In pre-term babies and those with fetal growth restriction, these energy stores are lower.

Extra energy is required not only for the developing fetus but also to fuel the increase in maternal physiological parameters. The resting metabolic rate is increased by around 20% and weight increases on average by around 12 kg.

Initially, there is an increased sensitivity to insulin, which leads to increased glycogen synthesis, increased fat deposition and an increase in amino acid transfer into cells.

After mid-pregnancy there is a degree of insulin resistance. The serum glucose level at this stage may therefore rise, a change presumably in the fetal interest as fetal glucose levels will also rise. The insulin resistance also leads to increased levels of serum lipids, which can be used by the mother as an alternative energy source to glucose. Although maternal amino acid levels fall, there is increased transport across the placenta.

Calcium homeostasis

Fetal skeletal development requires 20–30 g of calcium, and this need is met by increasing maternal intestinal absorption. There is usually, therefore, no maternal bone demineralization. Calcium transfer across the placenta is an active process occurring against a concentration gradient and it is therefore not surprising that maternal free calcium levels are not significantly changed. Serum protein and albumin fall as part of the plasma dilution of pregnancy so that total calcium is reduced. Vitamin D deficiency is commoner in pregnancy. Some recommends that all pregnant and breastfeeding women should take a daily supplement containing 10 μg of vitamin D.

Musculoskeletal System

Abdominal muscles are stretched to the point of their elastic limit by the end of pregnancy. Hormonal influence on the ligaments is profound producing systemic decrease in ligamentous tensile strength and an increase in mobility of structures supported by ligaments and may predispose the patient to joint injury especially in the weight-bearing joints of the back, pelvis and lower extremities. The pelvic floor muscles must withstand the weight of the uterus, the floor drops as much as 2.5 cm.

Progressive lordosis compensates for the anterior position of the enlarging uterus.

Increased mobility of sacroiliac, sacrococcygeal &pubic joints(not correlated to increased levels of maternal estrogen, progesterone &relaxin levels.

Joint mobility causes low back pain which is bothersome late in pregnancy.

Bones & ligaments of pelvis undergo remarkable adaptation

Relaxation of the pelvic joints, particularly symphysis pubis

Symphyseal diastasis

Postural changes:

During pregnancy, postural changes occur to accommodate for abdominal growth.

a. These changes include forward head, rounded shoulders, increased lumbar lordosis, hyperextended knees, and pronated feet.

b. The center of gravity changes, resulting in changes in balance.

c. Muscular changes are also typical. often noted alterations include shortened hip flexors, lower back musculature, and pectorals. Abdominal muscles, neck, and upper back muscle groups elongate. This may promote stretch weakness or adaptive shortening.

Bones and joints:

    There is tendency to decalcification of bones, sublaxation of joints due to softening of ligaments by relaxin hormone. It is more marked in sacroiliac joint and symphysis pubis, leading to waddling gait.

Nervous system

Functional changes may appear especially in neurotic women as :

-sleepy, depressed

-while others become irritable, excited and suffer from insomnia.

-The nausea and vomiting may have a neurotic element.

-Change of appetite such as refusal of some types of   food.

-Neuralgias.

Carpal tunnel syndrome 

Endocrine system

Pregnancy influences endocrine functioning in two main ways: 1) placental hormonal production and 2) by increased protein binding.

The placenta produces a number of hormones, including oestrogen, progesterone (which relaxes smooth muscle), human placental lactogen (which increases maternal glucose and lipids) and human chorionic gonadotrophin (which prevents degradation of the corpus luteum in early pregnancy).

Pregnancy is a diabetogenic state. Cortisol, progesterone, oestrogen and human placental if there is maternal insulin resistance, the maternal glucose level may rise pathologically. lactogen are all insulin antagonists, and tend to increase the glucose level. If the pancreatic islet β-cells are unable to produce sufficient insulin to balance this increase,

The placenta also produces corticotrophin-releasing hormone, which in turn stimulates maternal production of ACTH, leading to increased aldosterone and cortisol, which in turn contribute to the maternal fluid changes described above.

Roles of selected placental hormones:

Thyroid function:

                             In pregnancy, there is increased iodine uptake activity and the total serum levels of T3 and T4 are also raised. Only the unbound portion of thyroxine is metabolically active, however, and as oestrogens also induce synthesis of thyroid-binding globulin, the levels of free T3 and T4 remain within the normal range or may even fall slightly.

Pituitary function

                            Oestrogen stimulates the release of thyrotrophin-releasing hormone, which in turn increases prolactin production by the anterior pituitary. Prolactin stimulates breast growth antenatally, but lactation is usually inhibited by progesterone until after delivery of the placenta, when the prolactin acts with oxytocin from the posterior pituitary to stimulate milk production. Pituitary prolactin production is increased to such an extent in pregnancy (around 10 times the pre-pregnancy level) that the pituitary increases in size by around 135%.

Other functions of placenta apart of hormone synthesis will include:

Respiration, Nutrient transfer, als and o providing the mechanism for waste excretion. 

Examples of the mechanism of different mechanisms of placental transfer 

1.Passive diffusion (from a higher gradient to a lower one) e.g., CO2, O2, water.

2.Facilitated diffusion as with Glucose (by a carrier molecule).

3.Active transport by enzymatic action and using energy as in Amino acids, Ca, Fe, vitamins B and C, free fatty acid.

4.Organelle transport by pinocytosis as with IgG

Relaxin is a hormone secreted by the corpus luteum.  Relaxin softens connective tissue during pregnancy in preparation for  labour and delivery. When  the pelvis must open to allow for the birth of the foetus. Relaxin  is not specific to the pelvis. Other joints can also be affected.  Relaxin peaks in early and late pregnancy. Women with chronic joint instability may notice an increase in symptoms during these times.  Relaxin has also been speculated to increased in the  non pregnant women after ovulation and throughout the menstrual period. This may cause softening of the joints and pain in affected women.

Edema is present in the hands. feet. face and eyelids. This is due in part to sodium and water retention. 

Immunology

In pregnancy there is an immune-modulation, this changes in immune system is more favor of hmoral immune system than cell mediated immunity, Cell mediated immunity depends on T lymphocyte, Natural killer cells or macrophage, that ia why pregnant woman are at risk of intracellular organisms as viral infection e,g, Con vit 19 and H1 N1influenza virus. Humoral immune system will depend on antibody production by B lymphocyte and plasma cell.

Most human cells have a gene on chromosome 6 that codes for a particular protein called the human leucocyte antigen or ‘HLA’. Each of us has a unique HLA gene and the protein synthesized from this gene coats the surface of all the cells in our body, allowing our immune cells to recognize ‘self’ cells. If leucocytes identify a ‘non-self’ code, they initiate a process of cell destruction. The fetus is genetically unique and will have a different HLA complement from that of either parent. If a skin graft is taken from a child and grafted onto its mother, the graft will be rejected. Yet, while the fetus is ‘grafted’ onto the lining of the maternal uterus, it is not rejected.

WHY?

There must therefore be some protective mechanism, or mechanisms, to prevent immunological fetal rejection.

HLA has different subtypes. The classical genes, HLA-A, -B and -C, provide the highly individual molecules coding for ‘self’, and these molecules are absent on many of the placental cells. This would render these placental cells less susceptible tomaternal leucocyte recognition and therefore less liable to destruction. Some immunological reaction, however, may be important to prevent placental over-invasion, and some placental cells do express the classical genes, particularly HLA-C. Further modulation of this uneasy fetomaternal immune relationship may be modified by another HLA molecule, HLA-G, specific only to placental tissue. Much more work is required before these mechanisms are understood more clearly, particularly as it is becoming apparent that immunological disparity may lie behind recurrent miscarriage, fetal growth restriction and pre-eclampsia.