LM 15.1: Normal Physiologic Changes of Pregnancy

Question 1

what are maternal adaptations to pregnancy ?

Answer 1

almost every organ system changes in response to pregnancy, some more significantly than others

most changes resolve by 6 weeks post delivery once all of the hormonal influences have cleared

Question 2

how does the uterus change from non-pregnant to pregnant state?

Answer 2

not pregnant uterus: 70 grams, 10 mL cavity capacity

pregnancy uterus: 1100 grams after delivery, 5 L cavity capacity but up to 10 L if multiple gestation or abnormal amniotic fluid

Question 3

what causes growth of the uterus during pregnancy?

Answer 3

enlargement is not by production of new cells, but by hypertrophy of the myometrial cells already present

early in pregnancy, hypertrophy likely is influenced by estrogen

at approximately 12 weeks, the uterus is large enough to extend out of the pelvis

late in the 3rd trimester it is causing elevation of the diaphragm

Question 4

how does blood blow into the uterus change during pregnancy ?

Answer 4

blood flow into the uterus increases progressively throughout the pregnancy

2nd trimester: 450 ml/min of blood flow

at term: 500-750 ml/min

Question 5

what are the 3 layers of the uterine wall?

Answer 5

1. outer hoodlike layer

covers fungus and extends into ligaments

2. middle layer

interlaced with blood vessels, myocytes running in different directions

3. inner layer

sphincter like fibers around the tubal ostia and internal os of cervix

Question 6

how does myocyte structure in the uterus help with pregnancy ?

Answer 6

in the myometrium, there are myocytes running in different directions

they have a double curve to increase the interlacing of cells and strength

this allows for creating the strength of the contractions as well as the direction of the force towards the cervix

once placenta delivered, the uterus contracts down—these myocytes have now contracted around the vessels and stopped bleeding by mechanical means of closing the vessels

Question 7

what is the blood supply of the placenta?

Answer 7

spinal arteries

Question 8

which medications cause uterine contraction?

Answer 8

1. oxytocin
2. methylergonovine
3. carboprost (F2alpha prostaglandin)
4. misoprostol (E1 prostaglandin analog)

Question 9

how does the cervix change throughout pregnancy?

Answer 9

early in pregnancy, the cervix takes on a bluish tinge from the increase in vascularity and changes in the collagen network (aka Chadwick Sign)

during the majority of the pregnancy, the cervix has the responsibility of retaining the pregnancy (holding it in)

the mucous produced by the cervix during pregnancy is thick, tenacious and rich in immunoglobulins and cytokines so it may act as a barrier to infection

by delivery time, the cervical glands have proliferated to the point of contributing half of the cervical volume

for delivery, the cervical matrix changes, allowing cervical change/dilation in response to contractions. The mucous thins and the mucous plug (thick mucous that was in the canal) is released

at delivery, the cervix has dilated up to 10 cm to allow passage of the fetus (it may have dilated from 1 to 10 cm in under 24 hours or less!)

Question 10

what is the normal pH of the vagina? what maintains it?

Answer 10

between 3.5 and 6

it’s maintained by the production of lactic acid by Lactobacillus

Question 11

how does the vagina change during pregnancy?

Answer 11

1. epithelial thickening
2. connective tissue loosening
3. smooth muscle cell hypertrophy

Question 12

how does skin change during pregnancy?

Answer 12

found in up to 90% of women

most noticeable in women of darker skin tones

not fully understood, but thought to be due to higher levels of Melanocyte stimulating hormone – estrogen and progesterone may play a role

examples:
1. linea nigra

2. cloasma
3. striae gravidarum
4. angiomas
5. palmar erythema

Question 13

what is the linea nigra?

Answer 13

darkly pigmented vertical line found in the midline of the abdominal wall of pregnant women

Question 14

what is cloasma?

Answer 14

AKA melasma gravidarum or the mask of pregnancy

also can be found in association with combination oral contraceptive agents

Question 15

how does hair change during pregnancy?

Answer 15

1. anlagen phase is lengthened in pregnancy (growth phase)

2. telogen effluvium = excessive hair loss in the postpartum period

Question 16

how is water metabolism effected with pregnancy?

Answer 16

increased water retention caused by a reset of osmotic thresholds for thirst and vasopressin secretion

starts in early pregnancy and results in a decrease of plasma osmolality of 10 mOsm/kg –> by the end of the pregnancy, pregnant woman has retained approximately 6.5 L (14.3 lbs)

there may also be peripheral edema due to combination of decrease in osmolality and increase in venous pressure due to pelvic mass (pregnant uterus)

Question 17

how do glucose levels change in pregnancy?

Answer 17

1. mild fasting hypoglycemia
2. postprandial hyperglycemia
3. hyperinsulinemia
4. hepatic gluconeogensis is augmented especially in 3rd trimester

Question 18

what is gestational diabetes?

Answer 18

glucose intolerance that occurs during pregnancy and usually resolves by 6 weeks post delivery

because of the increased insulin resistance, diagnosis of diabetes increases

untreated gestational diabetes causes increased maternal AND fetal morbidity and mortality

Question 19

what are the risk factors for gestational DM?

Answer 19

1. history of gestational diabetes
2. multiple gestation
3. history of large for gestational age infant
4. high risk race or ethnicity
5. history of CVD
6. physical markers of insulin resistance like obesity, acnthosis nigricans
7. overweight
8. family history of DM
9. chronic HTN
10. history of PCOS

Question 20

what are the cardiovascular changes that occur during pregnancy?

Answer 20

1. systemic vascular resistance drops at 5 weeks
2. BP lowers around 16-20 weeks then rises after that
3. CO increases due to increased HR
4. blood volume increase
5. as diaphragm is pushed up, heart is shifted to the left and up, rotated on the long axis leading to larger cardiac silhouette on CXR and slight left axis deviation on EKG
6. exaggerated splitting of first heart sound, early systolic murmur without radiation
7. EF doesn’t change
8. supine hypotension due to the vena cava being compressed by uterus and decreasing venous return

Question 21

what is supine hypotensive syndrome?

Answer 21

arterial compression by the pregnant uterus occurring in the supine position usually in the 3rd trimester or 2nd trimester if multiple gestation

the vena cava is compressed markedly decreasing venous return resulting in supine hypotension and poor maternal and placental(fetal) perfusion

increase in the venous system due to the mass effect of the pregnant uterus leads to increased venous pressure in the pelvis and lower extremities which leads to increased:
1. venous varicosities of pelvis, vulva, vagina and legs

2. risk of DVT
3. incidence of hemorrhoids
4. lower extremity edema

Question 22

how is blood volume effected during pregnancy?

Answer 22

blood volume increases by 15% in the firs trimester and by 40-45% by 32-34 weeks gestation –> this is accomplished by increases in plasma volume and in erythrocyte numbers

increase in red cell production is due to increase in erythropoietin and is reflected with increase in reticulocyte count

Hb and Hct decline due to greater production of plasma than RBCs resulting gin a dilution decrease in Hb/Hct and decreased viscosity –> this protects the mother from negative effects of standing or lying on back resulting in impaired venous return and from anticipated blood loss with delivery

Question 23

how is coagulation/fibrinolysis effected during pregnancy?

Answer 23

pregnancy is a hyper coagulable state

coagulation and fibrinolysis are both augmented

level and rate of thrombin production increases progressively

1. increase in fibrinogen
2. increase in procoagulants
3. liver stimulated by estrogen

Question 24

what are the natural inhibitors of coagulation? how are they effected during pregnancy?

Answer 24

1. protein C
2. protein S
3. antithrombin

resistance to activated protein C increases during pregnancy

decrease in free protein S levels

Question 25

what are the structural changes that happen to the respiratory system during pregnancy?

Answer 25

1. subcostal angle increases from avg of 68.5 degrees to 103.5 degrees
2. diaphragm is elevated 4 cm from normal position in late 3rd trimester
3. thoracic circumference increases ~6 cm

Question 26

what are the physiologic lung changes that occur during pregnancy?

Answer 26

1. functional residual capacity decreases by 20-30%
2. residual volume decreases more than the expiratory reserve volume (ERV+RV = FRC)
3. inspiratory capacity increases by 5-10%
4. tidal volume and resting minute ventilation increase as pregnancy advances
5. peak expiratory flow rate increases with gestation
6. airway conductance increased
7. total pulmonary resistance decreased

lung compliance, maximum breathing capacity, and forced vital capacity are unaffected

Question 27

why does resting minute ventilation change during pregnancy?

Answer 27

resting minute ventilation increases due to:

1. stimulatory action of progesterone
2. low expiratory reserve volume
3. compensated respiratory alkalosis

Question 28

why do pregnant women note an increased desire to breath?

Answer 28

greater tidal volume during pregnancy lowers the PCO2 since you’re blowing off more CO2 and causing a respiratory alkalosis (PCO2 of 25-33 in 3rd trimester)

likely caused by progesterone which acts centrally to lower the threshold and raises sensitivity of chemorelfex response to CO2

this results in a lower HCO3 as well since it’s compensating for the respiratory alkalosis

it’s totally normal and can be misunderstood as a sign of CVD or respiratory disease

Question 29

how do pregnancy women compensate for the respiratory alkalosis that occurs during pregnancy?

Answer 29

O2 affinity in RBCs is increased (Bohr effect)

slight increase in pH stimulates increase in 2,3-BPG in RBCs

PO2 is unchanged

Question 30

how is the GFR effected in pregnant women?

Answer 30

increased GFR

25% by the 2nd week of conception!!!! 50% by the beginning of the 2nd trimester

occurs due to hypervolemia-induced hemodilution lowering the protein concentration and oncotic pressure of plasma entering the glomerular microcirculation

renal plasma flow increases by 80% by the end of the first trimester and then declines after 20 weeks

leads to:
1. increased frequency of urination due to increased in volume

2. decrease in serum creatinine (0.4-0.9)

Question 31

how are the kidneys effected in pregnancy?

Answer 31

1. glucosuria

can be normal due to increased GFR and impaired tubular reabsorption

2. proteinuria

due to increase in GFR and possible reduction of tubular reabsorption

300 mg/24 hrs compared to 150/24 hrs for non-pregnant female

Question 32

how are the ureters effected by pregnancy?

Answer 32

1. uterus enlarges, resists out of the pelvis and can compress the ureters at the pelvic brim
2. progesterone causes relaxation of the ureters = dilation and stasis
3. ureteral dilation; can lead to hydronephrosis

Question 33

how is the bladder effected during pregnancy?

Answer 33

as pregnancy progresses, the space for the bladder to expand with collected urine decreases

vesicoureteral reflex can occur

signs/symptoms:
1. urinary frequency

2. urinary incontinence
3. increased risk for UTI and pyelonephritis
4. higher risk of urosepsis

Question 34

what are the intestinal changes that occur during pregnancy?

Answer 34

1. intestines displaced upward – alters location of appendix and increases pressure on stomach
2. progesterone slows GI motility, relaxes esophageal sphincter and leads to delayed gastric emptying with labor and narcotics

leads to constipation, heart burn, increased risk of aspiration at time of cesarean or other surgeries

Question 35

what is hyperemsis gravidarum?

Answer 35

excessive nausea and vomiting during pregnancy

can lead to:

1. dehydration
2. ketosis
3. weight loss
4. electrolyte imbalance
5. alkalosis due to HCl loss
6. hepatic dysfunction

Question 36

how is the liver effected during pregnancy?

Answer 36

1. alkaline phosphatase almost doubles due to production of same by the placenta
2. serum albumin declines

liver enzymes, GGT and bilirubin should not rise and may be slightly lower

Question 37

how is the gallbladder effected during pregnancy?

Answer 37

1. contractility reduced

leads to increased residual volume; may be due to progesterone

2. increase of cholesterol saturation of bile
3. cholelithiasis

Question 38

how is the pituitary gland effected during pregnancy?

Answer 38

increases in size 135% largely driven by estrogen stimulated hypertrophy and hyperplasia of lactotrophs

normalized size by 6 months postpartum

Question 39

how do prolactin levels change during pregnancy?

Answer 39

at term, prolactin levels are 10 time what they are in non-pregnant women

they return to normal after delivery even in breastfeeding women

Question 40

how is the thyroid effected during pregnancy?

Answer 40

1. TRH has no change
2. thyroid gland production increases 40-100% to meet maternal and fetal demands so moderate enlargement occurs
3. TSH levels decline
4. TBG increases

Question 41

how are TSH levels effected during pregnancy?

Answer 41

TSH and hCG share the same α-subunit.

hCG has intrinsic thyrotropic activity and can cause thyroid stimulation

TSH levels decline in >80% of women in the first trimester, but remain in the normal range

Question 42

how are TBG levels effected during pregnancy?

Answer 42

thyroid binding globulin increases as a result of estrogen stimulation for higher liver production and lower metabolism rate due to sialylation and glycosylation of TBG

higher TBG increases Total T4 and Total T3 but does not change Free T4 or Free T3

maternal T4 crises the placenta and maintains normal fetal thyroid function so the fetus relies on lateral T4!