MATERNAL PHYSIOLOGY & ENDOCRINAL CHANGES DURING

NORMAL PREGNANCY

By

Dr. Ram Lochan Yadav

Introduction In all mammalian species, there are extensive

biochemical, physiological and structural changes during pregnancy:

Any female of reproductive age could be pregnant

Virtually every organ system affected

The causes of these changes are:

1.To provide a suitable environment for nutrition, growth and development of fetus

2 . To prepare the mother for the process of parturition and subsequent support of the new born baby.

Mission

Understanding the adaptations to pregnancy

Anatomical

Physiological

Anatomical adaptations

• Uterus

• Cervix

• Ovaries

• Fallopian Tubes

• Vagina & Perineum

• Breast

Physiological adaptations

• Neurological

• Respiratory

• Hematologic

• Cardio Vascular

• Gastrointestinal

• Hepatobiliary

• Urinary

• Metabolic

• Endocrine

• Musculoskeletal

• Weight Change

• Dermatological

• Ophthalmological

• Dental

Uterus

Non Pregnant Uterus

Pregnant Uterus

Muscular

Structure

Almost Solid Relatively thin –walled (≤ 1.5 cm)

weight ≈ 70 gm Approx. 1100 gm by the end of pregnancy

Volume ≤ 10 mL ≈ 5 L by the end of pregnancy

Mechanism Of Uterine Enlargement

Individual muscle fibres increasing in length by 15 fold along with specialized cellular connections (gap junctions); spiral arteries changed into floppy thin-walled vessel.

Stretching & marked hypertrophy &

hyperpalsia myometrial cells (d/t

high level of maternal estradiol &

progesterone

Accumulation of elastic tissue &

fibrous tissue, particularly in the

external muscle layer.

Uterine size, shape & position

First few weeks, original peer shaped organ

As pregnancy advances, corpus & fundus assumes a more globular form.

By 12 weeks, the uterus becomes almost spherical .

Subsequently, uterus increases rapidly in length than in width & assumes an ovoid shape.

With ascent of uterus from pelvis, it usually undergoes Dextrorotation (caused by the rectosigmoid colon on the left side)

Cervix As early as 1 month after conception the cervix

begins to undergo profound swelling, softening

&cyanosis due to : (estradiol & progesterone)

Increased vascularity & edema of the entire cervix.

Hypertrophy & hyperplasia of the cervical glands.

Endocervical mucosal cells produce copious amounts

of a tenacious mucus that obstructs the cervical canal

soon after conception(mucus plug)

Estradiol stimulates growth of the columnar

epithelium of cervical canal that becomes visible on

ectocervix called ectropion

Ovaries

Cessation of ovulation & arrest of maturation of new follicles.

Single corpus luteum is found in ovaries of pregnant women that contributes to progesterone production maximally during the first 6 to 7 weeks of pregnancy

This explains the rapid fall in serum progesterone & the occurrence of spontaneous abortion upon removal of the corpus luteum before 7 wks.

Fallopian Tubes

The musculature of the fallopian tubes

undergoes little hypertrophy

The epithelium of the tubal mucosa becomes

somewhat flattened

Vagina & Perineum

Increased vascularity prominently affects the vagina resulting in the violet color (chadwick sign).

Considerable increase in the thickness of the vaginal mucosa, loosening of the connective tissue, hypertrophy of smooth muscle cells.

Vaginal epitheliumthickerdesquamationacidic discharge

Breast changes

• Increased size and vascularity

warm, tense & tender

• Increased pigmentation of the nipple & areola

• Secondary areola appear

(light pigmentation around the 1ry areola)

• Montgomery tubercules appear on the areola

(dilated sebaceous glands)

• Colostrum like fluid is expressed at the end of the 3rd month

Breast changes

Volume haemostasis Fliud retention 8-10 kg of average maternal weight

Some innrease in intracellular water, but most marked expansion

occurs in ECF (↑by 7 liter,~40% above prepregnant), especially

plasma volume 70% increase in blood volume

Factors contributing to fluid retention:

Na & H2O retention: 900 mmol (3-4 mmol/day), ↑anti-natriuretic

hormone (aldosterone & deoxycorticosterone)

Plasma osmolality – resetting osmostat

Decrease thirst thresold

Decrease in plasma oncotic pressure by 20%: major contributing

to starling mechanism & peripheral edema

HAEMATOLOGY

↑ Erthropoietin & hPL in pregnanacy stimulate hemopoiesis

Erythrocytes rises (no. & size) by 20-30% after 16 wks

↑ in RBC mass is slower & lesser than the ↑ in plasma volume hemodilution physiological anemia of pregnancy

Total WBC count ↑ due to ↑ed polymorphonuclear leukocytes (d/t ↑ estrogen)

T & B lymphocytes counts do not change rather their function is suppressed pregnant women more suceptible to viral infections, malaria & leprosy

HAEMATOLOGY

COAGULATIONSeveral procoagulent factors (factors VII, VIII & X, & Plasma fibrinogen doubles) rise from the end of 1st

trimester hypercoagulable state (advantage or disadvantage??)

Antithombin III (inhibitor of coagulation) falls

ESR rises due to increase in fibrinogen favors rouleaux formation

Protein C (inactivates factor V & VIII)unchanged but protein S fall during 1st two trimesters

Plasma fibrinolytic activity is decresed

CardioVascular

Elevated progesterone & estrogen vasodilation

Endothelium derived vasoactive (eg.NO)

Vasodilation ↓TPR ↓afterload& BP, & perceived as

circulatory underfilling that acivates RAS↑ALD↑CO

Probably fall in baroreflex sensitivity as pregnancy

progresses & HRV falls & HR increases ↑CO

Small fall in SBP but greter fall in DBP. The BP then rises

steadly in parallel with ↑sympthetic activity (thus, ↑in PP).

MAP usually decreases during mid pregnancy & rises in 3rd

trimester remains at or below nomal (Why??)

No change in pressure in the right ventricle, WHY??

CardioVascular

Stroke volume

Heart rate

CO

SVR

Systolic BP

Diastolic BP

Mean BP

O2 Consumption

( 10%)

( 15%)

( 35%)

( 35%)

( 5-10 mmHg)

( 15 mmHg)

( 10%)

( 20%)

CardioVascular

ECG Changes

Increased heart rate ( 15%)

15° left axis deviation.

Inverted T-wave in lead ІІІ.

Q in lead ІІІ & AVF

Unspecific ST changes

Pulmonary Function ↓RV & FRC due to elevation of

diaphragm. No change in VC, pulmonary compliance, FEV1 & PEFR.

Though respiratory rate is little changed, TV↑(~40%)---> ↑alveolar ventilation. TV is ↑ed as progesterone ↓ the thresold & ↑ the sensityvity of medulla oblogata to CO2

Pco2 is lowest in early gestation (↑ Va + ↑CA in RBC) facilitates CO2 transfer from fetus to mother; ↓maternal plasma osmolaity (due to ↓HCO3- )

↑2,3 DPG in maternal RBCs

Pulmonary Function

Fig 5.9 baker

Gastrointestinal

Due to relaxation of smooth muscle ( d/t high progesterone level)

Pyrosis (heartburn) is common &is caused by reflux of acidic secretions into lower esophagus & decreased tone of sphincter.

Gastrointestinal

Slight reduction in gastric secretion and diminished gastric motility result in slow emptying and may lead to nausea.

Reduced intestinal motility lead to increase time for water absorption , which tends to induce constipation

Gastrointestinal

Growth of conceptus and uterus

leads to increase appetite and

thirst.

In late pregnancy pressure of the

uterus reduces capacity for large

meals leads to frequent small

snacks

Hepatobiliary

No distinct changes in morphology & size of liver in pregnancy. Despite this, there is increase in diameter of portal vein &its blood flow

Serum alkaline phosphatase almost doubles (heat stable placental alkaline phosphatase isozymes)

Serum AST,ALT,GGT, bilirubin levels are slightly lower than non pregnant normal values

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

Gallbladder changes

Reduced contractility of the gallbladder & rlaxation of biliary tract. Hence, bile flow decreases.

Progesterone impairs gallbladder contraction by inhibiting CCK mediated smooth muscle stimulation (1ry regulator of gallbladder contraction)

Impaired motility leads to stasis, associated with increase in cholesterol saturation of pregnancy.

Pregnancy causes intrahepatic cholestasis from retained bile salts.

Cholestasis of pregnancy is linked to high levels of estrogen which inhibit transductal transport of bile acids.

Urinary system Kidney increases in size mainly

because parenchymal volume rises

by about 70% with marked

dilatation of caluces, pelvis &

ureters.

↑ RBF(65-75%)↑ GFR (50%)

↑clearance of no. of substances

Plasma concn of urea & creatinine

fall to mid pregnanacy & increase at

term.

Frequency of micturition is a

common symptom of early

pregnancy and again at term.

Urinary System

Glycosuria - may rise 10-fold as the greater filterd

load exceeds the proximal tubular Tmax for glucose

(~1.6-1.9 mmol/min)

Excretion of most of amino acids increases

microalbuminuria (0.3 g/day)

Urinary Calcium excretion is increased even though

tubular reabsorption is enhanced under the influence

of 1,25-dihydrxyvitamin D.

↑TBW (~20%) with fall in plasma osmolality about

4-6 wks of pregnancy (d/t hCG) edema

Neurological

Women often report

problems with attention,

concentration, &memory

throughout pregnancy &

early postpartum period.

Neurological

In a longtudinal study done by keenan

&colleagues (1998) investigating memory

in pregnant women by a matched control

group, they found pregnancy related

decline in memory limited to 3rd trimester

an attributable to depression, anxiety, sleep

deprivation or any other physical changes

associated with pregnancy

Neurological

Zeeman and co-workers (2003) used MRI to measure cerebral blood flow across pregnancy in 10 healthy women.

They found that mean blood flow bilaterally in the middle and posterior cerebral arteries decreased progressively from 147 and 56 ml/min when non pregnant to 118 and 44 ml/min late in the third trimester, respectively.

The mechanism and clinical significance of this decrease, and whether it relates to the diminished memory observed during pregnancy is unknown.

Musculoskeletal Progressive lordosis compensates

for the anterior position of the

enlarging uterus.

Increased mobility of sacroiliac,

sacrococcygeal &pubic joints

leading to wadling gait, correlated

to increased levels of maternal

estrogen, progesterone & relaxin

levels.

Joint mobility causes low back

pain which is bothersome late in

pregnancy.

Dermatological

Reddish, slightly

depressed streaks

commonly develop in

the skin of the abdomen

and sometimes in the

skin over the breasts

and thighs.

Striae gravidarum

Dermatological

The midline of the

abdominal skin “linea

alba” becomes

markedly pigmented,

assuming a brownish-

black color to form the

linea nigra.

Dermatological

chloasma or melasma

gravidarum

Weight Changes

Metabolic changes, accompanied by fetal growth, result in an increase in weight of around 25% of the non-pregnant weight.

Approximately 12.5 kg in the average woman (usually at a rate of 0.5 kg/wk for the last 20wks).

Weight Changes

5kg is the fetus, placenta, membranes and amniotic fluid

and the rest maternal stores of fat and protein and increased

intra and extra-vascular volume.

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

9.70-14.55Kgtotal=Muscle and fat 0.48-2.91 kg

Ophthalmic

Decrease in intraocular pressure due to increased vitreous outflow

Decreased corneal sensitivity especially, late in gestation

Slight increase in corneal thickness thought to be due to edema

Visual function remains unaffected except for transient loss of accomodation

Dental

Gums may become hyperemic & soft during

pregnancy and may bleed if mildly traumatized

as with a toothbrush GINGIVITIS OF

PREGNANACY

Dental

Epulis gravidarum:

regress 1-2 mths after

delivery excise if

persistent or excessive

bleeding -

PREGNANACY

GINGIVAL TUMOR

Human Chorionic Gonadotropin secreted by the syncytial trophoblast

cells, starts at 8-9 days after

ovulation, maximum10-12 wks of

pregnanacy.

prevent involution of the corpus

luteum at the end of sexual cycle.

Instead, it causes the corpus luteum

to secrete sex hormones—

progesterone & estrogens (for the

next few months)

hCG acts interstitial cell

(stimulating effect on testes of male

feteus) to produce testesterone untill

the time of birth

Estrogens by the Placenta

Trophoblast cell of placenta form estradiol, estrone, & estriol from dehydroepiandrosterone & 16-hydroxydehydroepiandrosterone, which are formed from adrenal glands of mother & fetus

Functions:

Enlargment of mother’s uterus, breasts & growth of ductal structure, external genitalia

Relax the pelvic ligaments, sacroiliac joints become limber, pubic symphysis becomes elastic

progesterone by the Placenta

Functions:

Causes decidual cells to develop in uterine endometrium & provide nutrition

Prevent uterine contractions from causing spontaneous abortion

Development of conceptus before implantation

During pregnancy helps estrogen prepare the mother’s breasts for lactation

Human chorionic somatomammotropin (hCS):

Partial development of animal’s breast & lactation (also K/A hPL)

Acts like GH; ↓insulin sensitvity & ↓glucose utilisation,

& release free fats in mother to provde more glucose to

fetus

The hypothalamus & pituitary gland

Size of anterior pituitary lobe increases (2-3 times) due to growth of prolactin secreting cells. Prolactin secretion increase by 10-20 times from the end of 1st trimester

Hypothalamo-pituitary-ovarian axis is suppressed by high level of sex steroids. This decrease LH & FSH secretion & thus prevents ovulation in pregnancy.

TSH secretion responds normally to hypothalamic thyrotropin-releasing hormone (also formed by placenta)

ACTH concentrations rise during pregnancy partly because of placental synthesis of ACTH & corticotropin-releasing hormone & do not respond to normal control mechanisms

THE ADRENAL GLAND

Plasma total & unbound cortisol, cortsol binding globulin (CBG) & other corticosteroid concentration increase

Excess glucocorticoid inhibit fetal growth . However, the placenta synthesizes a pregnancy-specific 11β-

hydroxysteroid dehydrogenase, which inhibits transfer

of maternal cortisol.

THE THYROID GLANDMaternal iodine requirements ↑ because of active

transport of iodine to feto-placental unit & because ↑ed iodine renal clearance. Because the plasma level falls, thyroid gland increases iodine uptake from the blood. If there is dietary insufficiency,thyroid gland hypertrophies.

Parathyroid glands & Ca metabolism

The increased demand of Ca for fetal growth is achieved by increased absorption of Ca form GIT by vit. D & by increase in PTH secretion--- so, Ca supplement is imp.

Maternal total plasma Ca falls as albumin level also falls, but unbound ionized Ca unchanged.

PTH regulates synthesis of 1,25-dihydroxycholecalciferol (vit. D) in proximal convoluted tubule.

PTHrP, from fetal parathyroid gland & placenta, is transferred to maternal circulation & affects Ca haemostasis by acting trough PTH receptor

Renal hormones

RAS is activated from early oregnanacy

A vasodilator component of RAS has recently been described in which angiotensin 1-7 is the agonist, which rises during pregnancy, which stimulate the release of NO & prostacyclin

Erthropoietin synthesis stimulated by hCG

THE PANCREAS

No. of β cells & size of islet of Langerhan’s increase in

pregnancy

Energy requirements

BMR increased by ~5% by 3rd trimester

Additional protein (30gm/day): to meet the demand of the growing fetus, placenta, uterus, and breasts, as well as the increased maternal blood volume.

iron (60 mg/day): to support the expanding maternal hemoglobin mass, the placenta, and the fetus . iron uptake increased in pregnancy (from 1.5 to 7 mg/day)

Folate (400 to 800 μg/day): for blood cells formation

Carbohydrate s & lipids Pregnancy is hyperlipiadaemic & glucosuric

After mid pregnancy insulin resistance develops progressively (why??) & plasma glucose concentration rise.

Resistani is beneficial to fetus as glucose crosses the placenta readily & fetus uses glucose as its primary enery substrates.

Increased maternal blood glucose stimulates glycogen synthesis & storage, deposition of fat & transport of amino acids into cells.

↑ VLDL, HDL, free fatty acids, triglycerides

Preclampsia & eclampsia rapid rise in BP to hypertensive levels during the last few

months of pregnancy & with leakage of large amounts of protein into the urine. This condition is called preeclampsia or toxemia of pregnancy.

characterized by excess salt and water retention by the mother’s kidneys and by weight gain and development of edema and hypertension , impaired function of the vascular endothelium, & arterial spasm in many parts of the mother’s body, especially in the kidneys, brain, and liver.

Both the renal blood flow and the glomerular filtration rate are decreased, which is exactly opposite to the changes that occur in the normal pregnant woman.

Preclampsia & eclampsia

Causes: unknown

results from some type of autoimmunity or allergy in the mother caused by the presence of the fetus

caused by excessive secretion of placental or adrenal hormones

insufficient blood supply to the placenta

increased levels of inflammatory cytokines such as tumor necrosis factor-a and interleukin-6.

Dewhurst’s textbook of Obstetrics & Gynaecology, 8th

edt.

Obstetrics by Ten Teachers, N. Baker- 18th ed.

Textbook of medical physiology- GK Pal

Textbook of medical physiology- Guyton, 11th ed

Textbook of medical physiology- Walter F. Boron

References: