maternal physiology

Physiological changes of pregnancy and labor
This lecture we will outline the major maternal physiological adaptations to pregnancy.‎
Pregnancy: ‎
it starts by the fertilization of the secondary oocyte by the male sperm forming the fertilized ‎
ovum which pass from the site of fertilization (ampulla of the tube) to the uterus, and ‎
Implantation: Occur in the 5-7th days after fertilization by the effect of proteolytic enzymes ‎
from the trophoblastic cells which digest the cells of the endometrium.‎
The placenta is formed by proliferating cells from blastocyst, trophoblast, and the ‎
endometrium.‎



Function of the placenta:‎
The development of the placenta with its villi surrounded by lakes of maternal blood in the ‎
large blood sinuses serves many functions.‎
Its main function is to carry nutrients from the mother to the fetus and the waste products ‎
from the fetus to the mother.‎
Oxygen is transmitted by simple diffusion, the dissolved O2 in the maternal blood pass to the ‎
fetal blood by means of pressure gradients between maternal and fetal blood (20mmHg).‎
CO2: which is formed in the fetus and excreted by diffusion through the placental membranes ‎
because of high solulability CO2 diffuse 20 times more rapid than O2. ‎
GLUCOSE: TRANSFERRED BY FACILITATED DIFFUSION BY MEANS OF A ‎
CARRIER MOLECULES IN THE TROPHOBLASTIC CELLS.‎
OTHER NUTRIENTS TRANSFERRED BY SIMPLE DIFFUSION ARE FATTY ACIDS, ‎
Na, K, Chloride…‎
Fetal waste products are excreted by simple diffusion through the fetal memb. Depending on ‎
a concentration gradient.‎

Maternal response to pregnancy
Major adaptations in maternal anatomy, physiology, and metabolism are required for ‎
successful pregnancy. Nearly every organ system is affected. ‎
Understanding these changes helps to distinguish normal physiology from pathological ‎
disease states. ‎
The changes that occur in the maternal body are numerous:‎
Systemic, reproductive, urinary, respiratory, digestive and endocrinological:‎

Systemic changes:‎

Volume homeostasis:‎
Pregnancy is a condition of chronic water overload (fluid retention), 8-10 kg of water is ‎
retained, the majority of it goes into the ECF ( MOST OF IT CONTRIBUTE TO THE ‎
PLASMA VOLUME EXPANSION) and this will lead to increased COP and increased ‎
urinary blood flow.‎
There is active Na and water retention: ‎
‎1. Changes in osmoregulation. ‎
‎ 2. Renin-angiotensin system.‎
Osmoregulation: ‎
Na retention increases 900 mEq but serum Na decreases 3-4 mmol/l ‎
Plasma osmolality decreases 10mOsm/kg ‎

In the kidney: ‎
Enhanced tubular reabsorption of Na secondary to aldosterone, estrogen and ‎
deoxycorticosterone. ‎
Increased GFR and Atrial Natriuretic Peptide favor Na excretion.‎

CVS:‎
Because of fluid retention:‎
‎1- Decrease Hb concentration.‎
‎2- Decrease HCT.‎
‎3- Decrease S.albumin.‎
‎4- Increased stroke volume.‎
‎5- Increased renal blood flow.‎

Heart : clinically
‎*Displaced to the left and upward ‎
‎*Apex is moved laterally ‎
‎*Apparent cardiomegaly on chest x-ray ‎
‎* systolic flow murmurs at left lower sternal border.‎

‎30-50% increase in CO (from 5 liters in the non pregnant state to 7 L) ‎
‎*CO= SV x HR ‎
HR: ‎
‎*Increases as early as 5 weeks GA ‎
‎*Peaks at 32 weeks at 15-20 beats above baseline(20% increase) ‎
SV: ‎
‎*Increases as early as 8 weeks GA ‎
‎*Peaks at 20 weeks with a 20-30% increase.‎

‎*BP= CO x SVR systemic vascular resistance ‎
SVR decreases to a minimum at midpregnancy with a gradual rise towards term but still 20% ‎
lower than nonpregnant ‎
the reduction in SVR due to: ‎
‎-Hormonal vasodilation due to progesterone,‎
‎-NO, prostaglandins, others.‎

BP changes: ‎
‎*Nadir by midpregancy ‎
‎*Increases to baseline in third trimester‎
‎*diastolic BP is measured by the 4th korotkoff sound(muffling) and nowadays they depend on ‎
the 5th sound (disappearance) which is more accurate.‎

CO increased during labor between 17 – 35% of the normal value‎

Haematological changes: ‎
‎*40-50% increase in blood volume beginning at 6 weeks and plateaus at 30 weeks ‎
‎*both plasma volume and cell mass increase ‎
‎*Physiologic anemia of pregnancy maximally at 30 weeks ‎
‎*Increase in erythropoietin and reticulocyte count‎

The increase in plasma volume is by effect of fluid retention lead to:‎
Decreased red cell count
Decreased Hb concentration (from 13.3 to 10.9g/dl
Decreased HCT
The platelet count slightly decreased ‎

Other parameters are elevated during normal pregnancy:‎
WBC 9 ×10 9 /L may reach up to 20×10 9 /L mainly by neutophilia.‎
Plasma fibrinogen increased and this contribute to the elevation of ESR during pregnancy‎
There is reduction of the plasma fibrinolytic activity‎

Iron Metabolism: ‎
‎*1000mg iron requirement, about 3.5 mg/d, 375 mg to form fetal blood, 600 mg for maternal ‎
blood. ‎
‎*Requirements increase in third trimester ‎
‎*Fetus receives Fe through active transport‎

Fe supplementation: ‎
‎*Fe supplemention usually not needed before 20 weeks ‎

Coagulation System: ‎
‎*Hypercoaguable state:‎
‎ Increased venous stasis ‎
‎ Changes in the coagulation cascade

Reproductive organs:‎
The ovary: change its position to become an abdominal organ when it is pulled up by the ‎
growing uterus, becomes hyperemic, and functionally ovulation is stopped.‎

Uterus: the rising E & P in the maternal blood lead to hyperplasia and hypertrophy of the ‎
myometrial cells which lead to increase in the weight from 50-60 g to 1000 g, 30 cm in length ‎
and 23 cm in width at term, with the formation of the upper and the lower segments.‎
The growth in the early pregnancy is mainly by hyperplasia while in the 2nd half the growth is ‎
by hypertrophy which is stimulated by growing fetus and uterine distension.‎
At term 500-700 ml of blood flow to the uterus and myometrial contraction is the 1st defense ‎
mechanism against bleeding after labor.‎
‎ ‎
The cervix: becomes swollen, and softer by the effect of E &P ‎
E lead to the growth of the columnar epith. Of the endocervical canal which appear on the ‎
ectocervix as the ectropion which bleeds easily on touch. the mucous is more viscous and ‎
opaque to close the cervical canal against the ascending infection, The cervix becomes bluish ‎
in color because of high vascularity.‎

Vagina: E lead to thickening of the epith. Which desquamate leading to increased vaginal ‎
discharge and becomes more acidic PH( 4.5 – 5) because of the action of the lactobacilli on ‎
the glycogen this high acidity is protective against ascending infection but favored by candida ‎
albicans.‎
The vagina also becomes more vascular (bluish in color).‎
Ferning sign is completely absent during normal pregnancy. ‎

Urinary System: ‎
‎ Anatomic Changes ‎
‎ *Renal hypertrophy ‎
‎ *Dilation of renal pelvis/calyces: ‎
‎ -Predisposition to pyelonephritis in the presence of assymptomatic bacteriuria ‎
‎ *Dilatation of ureters to 2 cm because of compression by the gravid uterus and by the effect ‎
‎ of Progesterone which induce smooth muscle relaxation.‎

Renal Hemodynamics and function: ‎
‎*Renal blood flow is increase ‎
‎*GFR increases. ‎
‎*Serum Creatinine and BUN levels decrease ‎
‎*Glycosuria occurs due to exceding of maximum tubular reabsorptive capacity ‎
‎*No increase in proteinuria ‎
if proteinuria is present it indicates pathological condition

Respiratory Changes: ‎
‎*Mechanical changes (earlier than mechanical pressure of rising uterus) ‎
‎ Chest circumference expands ‎
‎ Subcostal angle increases ‎
‎ Transverse diameter increases ‎
‎ Level of diaphragm rises ‎
‎ Respiratory muscle function is not affected by pregnancy‎

Pregnancy is a condition of:‎
‎*Chronic hyperventilation which is Progesterone induced ‎
‎*Respiratory rate is unchanged.‎

Gas Exchange ‎
‎*Hyperventilation leads to ‎
‎ deceased PCO² ‎
‎ Increases CO² gradient between fetus and mother ‎
‎ ‎
Digestive Tract Changes: ‎
‎ ‎
‎*Stomach: ‎
‎ Delayed gastric emptying time ‎
‎ Gastro oesophageal reflux due to: ‎
‎ Esophageal dysmotility ‎
‎ Gastric compression due to enlarging uterus ‎
‎ Decrease sphincter tone

Small bowel ‎
Motility is reduced due to progesterone allowing for more efficient absorption ‎
Large bowel ‎
increased transit times allows for both water and sodium absorption

‎*LiverSize and histology are unchanged ‎
‎*Spider angiomas and palmar erythema due to elevated estrogen level ‎

Skeletal and Postural Changes ‎
‎ ‎
‎*Lordosis of pregnancy--> progressive increase in anterior convexity of the lumbar spine to ‎
Preserves center of gravity ‎
‎*Ligaments of the symphysis and sacroiliac joints loosen during pregnancy due to relaxin ‎
which is secreted from the placenta in preparation for labor.‎

Skin changes: ‎
‎ ‎
‎*Hyperpigmentation of skin (cloasma), skin hyperemia, stria gravidarum on the abdomen, ‎
upper thigh and the breasts due to elevated level of cortisol which lead to weakness and ‎
breakdown of connective tissues on overstretching.‎
Increased activity of sweat glands and sebaceous glands. ‎


Parturition
Means birth of the baby, toward the end of the pregnancy the uterus increase its excitability.‎
The mechanism responsible for initiation of labor is still unknown? due to hormonal and ‎
mechanical factors. Strong uterine contractions develop ended by expulsion of the fetus‎
‎.‎
‎1- Hormonal factors: in the mother increase estrogen to progesterone ratio, and increased ‎
secretion of the oxytocin by the posterior pituitary.‎
P inhibits uterine contractions during pregnancy but there is no evidence it decreases near ‎
term.‎
E: a rising level of E during pregnancy sensitizes uterine muscles and makes it more easily ‎
responding to stimuli like oxytocin but there is no evidence of increased level prior to labor.‎
Oxytocin it can induce and augment labor but there is no increase level prior to delivery.‎
‎

In the fetus:‎
Fetal adrenal glands may play part in the initiation of labor there is evidence that ‎
anencephalic fetus has defective adrenal cortex, this pregnancy usually is prolonged..‎
‎ Increased oxytocin, increased cortisol, increased prostaglandin from the fetal membrane,‎
PG present in large amount in the decidua of late pregnancy, and synthetic PGs are used in ‎
induction of labor when placed vaginallyto stimulate uterine muscles contractions. ‎
‎2- Mechanical factors: stretching of the smooth muscle lead to inccreased contractility, so ‎
contractions can be induced by fetal movements.‎
But the question is why the uterus remains quiescent during the whole pregnancy and ‎
contracts only at its end?‎
‎*Over distended uterus: probably there is a limit for uterine distention that can be reached at ‎
term, which explain why twin pregnancy or polyhydramnios develop preterm labor? probably ‎
because of overstretching.‎

‎*Rupture of the amniotic membranes stimulate labor but labor can start without rupture of ‎
membranes
‎*The level of the intracellular Ca ion when raised leads to stimulation of contractions so we ‎
use the calicium chanel blockers and the beta adrenergic agonists to get uterine relaxation, ‎
while PG and oxytocin elevate Ca ion levels.‎
‎*The gap junction between myometrial cells increase in no and size near term which is ‎
stimulated by PG.‎
‎

*The onset of parturition is thought to depend on interaction between fetal tissues(membranes ‎
and placenta) and maternal tissues(decidua) both contain increasing amounts of PG which ‎
initiate labor partly by stimulating uterine contraction and partly by ripening of the cervix.‎

‎*The baby is delivered and this process is called labour, and the contractions are called labour ‎
contractions

‎*Labor contractions continue to occur by a +ve feedback mechanism when the uterine cervix ‎
is stretched by the fetal head this will lead to contractions of the uterine body and increase the ‎
oxytocin secretion by the posterior Pituitary.‎


Breast changes and lactation:‎
The breast enlarge in size early in pregnancy and becomes lobular in texture with dilated ‎
veins under its skin. The nipple enlarge in size, becomes darker in color and erectile. The ‎
areola is enlarged and darkened.with the growth of Montgomery tubercle.‎
Growth of the ductal system, role of estrogens: the placental estrogen cause ductal system of ‎
the breast to grow and branch, and the stroma increase in quantity with laying down of fat.‎
Other hormones essential for growth of ductal system are:‎
‎* G.H‎
‎* Prolactin‎
‎* Adrenal glucocorticoid
‎* Insulin‎

Development of the lobule alveolar system-role of progesterone: ‎
P work synergistically with E and other hormones leading to the development of the alveoli ‎
and lobules, with secretory changes in the alveoli
Colostrum is secreted from the middle of pregnancy.‎
Initiation of lactation-function of prolactin:‎
E and P --> breast growth but inhibit milk secretion, therefore no milk is produced in ‎
pregnancy.‎
Once the baby is born---> lowering of E and P and therefore removal of suppression on the ‎
milk production.‎

Ejection or let-down process in milk secretion-function of oxytocin:‎
Milk is secreted continually in the alveoli but not flow easily into the ducts and the nipples.‎
The milk ejection is both a neurogenic and hormonal process by the pit. Oxytocin
The 1st few sucks of the baby produce no milk flow but stimulation of the nippleàsensory ‎
impulses to the spinal cord to the hypothalamus to the pituitary gland to secrete both oxytocin ‎
and prolactin.‎

Oxytocin secreted in the blood reaching the breast leading to contraction of the myoepithelial ‎
cells surrounding the alveoli leading to ejection of the milk into the ducts then the baby can ‎
get milk after 30 sec. to 1 minute after starting of suckling leading to milk flow from both ‎
breasts
‎.‎

‎ Endocrinological changes of pregnancy:‎
Hormones produced from the uterus:‎
Placental hormones:‎
Human chorionic gonadotropin( hCG), estrogen, progesterone, and human chorionic ‎
somatomamotropin (hPL) are all placental hormones and essential for normal pregnancy‎

hCG:‎
‎ is a glycoprotein produced by the syncytiotrophoblast cells into the maternal blood consist of ‎
‎2 parts a and b subunits, and can be detected in the maternal blood from the 9th day of ‎
fertilization and its level in the plasma doubles every 2 days and reach maximum value at ‎
about 10-12 wks 50 000 -100 000 IU / L and then decrease toward the end of the pregnancy ‎
reaching half its level at 18 – 20 wks. hCG detectable in urine between 30 – 60 days‎
Its main function is to maintain the corpus luteum of the pregnancy to secrete E & P; other ‎
function is to induce immunological tolerance in the mother.‎
In the fetus the hCG stimulate the interstitial cells of the testes to secrete testosterone to ‎
enhance the development of the male sex organs and descent of the testes and stimulation of ‎
fetal adrenals. ‎
The b subunit is unique to pregnancy and used for the diagnosis of pregnancy by urine and ‎
blood tests, while a subunit is shared with other hormones like the FSH, LH, and TSH.‎

Estrogen:‎
‎ produced by the placenta increasing toward the late part of the pregnancy to reach up to 30 ‎
times the normal female level.‎
E produced by the placenta from precursors from maternal and fetal adrenals which secrete ‎
weak androgens that are converted by the placenta to E.‎
E functions: ‎
enlargement of the mother uterus from 50gm to 1000 gm, angiogenesis, stimulation of protein ‎
synthesis ans cholesterol metabolism in the liver, Na and water retention, enlargement of the ‎
breast and development of the duct structure, enlargement of the mother external genitalia, ‎
relaxation of the maternal ligaments in preparation to labor in addition to many other ‎
functions.‎

Progesterone:‎
Its functions:‎
Formation of the decidua, relaxation of the uterus maintaining the pregnancy, also help E in ‎
preparing the breast for lactation, vasodilatation, natriuretic, hyperventilation, thermogenic ‎
and increase thirst, appetite and fat deposition. Affect the nutrition and cleavage of cells in ‎
early embryo, it cross the placenta to be converted to cortisol in the fetal adrenals.‎
P is synthesized from cholesterol which is derived from LDL. The placenta produces at term ‎
‎250 mg P per day most of it bound to CSBG and only 5-15% is free. The increase in plasma ‎
level is 10 times quantitatively greater than the plasma level of E, but toward the end of ‎
pregnancy this ratio is inverted leading to initiation of labor. ‎
Other hormones produced by the placenta are: like most of the hormones secreted from the ‎
pituitary and the hypothalamus
‎ hPL is a polypeptide,and is a general metabolic hormone for the mother and the fetus, also ‎
have a prolactin like effect on the breasts. ‎
Relaxin: ‎
produced by the C.L and the placenta causing relaxation of the maternal uterus and ligaments.‎
Prolactin: present in high concentration in the AF in early pregnancy till the 20 wks then ‎
decreases, is secreted from the decidua and its function is to regulate the electrolyte and fluid ‎
balance in the AF and the fetus, it increase myometrial contractility, the main source in the ‎
mother is the pituitary, its level is decreased in normal labor in the mother but surges 2 hours ‎
after labor.‎
Other endocrine effects of pregnancy:‎
Most of the maternal endocrine glands react to placental hormones and metabolic load on the ‎
mother, like the pitutary gland, thyroid and parathyroid gland enlarge by about 50% during ‎
pregnancy.‎


Diabetogenic effects of pregnancy ‎
‎*hPL--> lipolytic and anti-insulin it antagonize the action of insulin ‎
‎*Cortisol which is elevated in normal pregnancy ‎
‎*Prolactin ‎
‎*Estrogen and progesterone ‎
Fetal glucose levels are 20 mg/dl less than maternal values ‎
Placental glucose transport is carrier mediated facilitated transport that is energy independent

Pancreas and Fuel Metabolism ‎
‎*Physiologic glucose intolerance to insure continuous transport of nutrients from mother to ‎
fetus ‎
‎*Fasting hypoglycemia ‎
‎*Postprandial hyperglycremia ‎
‎*Hyperinsulinemia due to insulin resistance induced by placental hormones‎

Thyroid Physiology ‎
‎*Euthyroid state ‎
‎*Slight thyromegaly ‎
‎*Free T4 and T3 remain normal but the total hormones are elevated because of the increased ‎
TBG. ‎
‎*Fetal thyroid active by 12 weeks‎
‎ ‎
Pituitary gland ‎
‎*Enlarges due to proliferation of prolactin-secreting cells ‎
‎*Prolactin levels are increased (ten times higher at term) to prepare breasts for lactation

Wt gain:‎
‎*Addition of 300 kcal/day ‎
‎*the mother gain about 24 pounds during pregnancy mainly in the 2nd and 3rd trimesters of ‎
pregnancy ‎
‎7 p by the baby ‎
‎4 p by the placenta A.F, and membranes ‎
‎9 p by the maternal body--> 6 p ECF ‎
‎ -->3 p by fat ‎
‎2p by the uterus ‎
‎2 p by the breasts‎
There is increased BMR especially in the 2nd half of pregnancy leading to increased calories ‎
requirements, and increased sensation of heat.‎
Diet: the growth of the fetus mainly in the last 2 mo of pregnancy, suppliments of iron, Ca, ‎
phosphate, proteins, vit. D, and vit K.‎
Plasma lipids increased
TG Is doubled
LDL is increased
Cholesterol incr.‎
FFA is doubled