Pathophys Normal Pregnancy 2020 21

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Normal Pregnancy

Danielle Cullen, M.D.


Dr. Cullen is a former Drexel faculty member. Direct questions about this IL to Drs. Baranoski or Farabaugh.

Link to Full Video (46 minutes long)

Learning Objectives
Part 1
1. Describe the process of fertilization and implantation
2. Review basic embryology
3. Identify maternal physiologic changes associated with pregnancy
4. Review placental physiology and fetal circulation
Part 2
5. Discuss the basics of prenatal care and normal labor.

NORMAL PREGNANCY: PART 1 (27 minutes)

Fertilization

-egg is released from the ovary in metaphase II surrounded by the cumulus oophorus (granulosa cells)
and the clear zona pellucida

-at the same time sperm is moving through cervical mucus and uterus
Sperm undergoes capitation and acrosome reaction

-sperm and egg meet in the ampulla of the fallopian tube

-sperm passes the zona pellucida, attaches to the cell membrane and enters the cytoplasm

-male and female pronucleus are present after the completion of a second meiotic division
Each pronucleus contains a haploid set of chromosomes
The nuclear membrane disappears and a diploid set of chromosomes is re-established

-Intercourse must occur prior to ovulation for successful fertilization to occur

-once the zygote is formed the cells will continue to divide

-This division allows for the potential for twinning


Twinning may occur at any stage until the formation of the blastula
Occurs by the separation of the two cells produced by cleavage
Each cell has the potential to develop into an embryo
Types of Twins
Diamniotic/dichorionic- prior to three days post fertilization
Diamniotic/monochorionic- 4-8 days post fertilization
Monoamniotic/monochorionic- 9-12 days post fertilization
Conjoined- 12 days or more post fertilization

-The embryo continues to divide as it travels through the fallopian tube


-Enters the uterus in 3-4 days after fertilization

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Implantation

Implantation can be as early as 6 days after fertilization, usually 3 days after embryo enters the uterus

The zona pellucida must be removed prior to implantation


Endometrial capillaries come in contact with the invading syncytiotrophoblasts and are engulfed to
form venous sinuses- generally 7.5 days after conception

The endoplasmic reticulum of the syncytiotrophoblasts is responsible for production of human


chorionic gonadotropin (HCG)
HCG enters the maternal circulation which allows for the corpus luteum to be
maintained Corpus luteum maintains the pregnancy until the placenta takes
over.
Progesterone is steroid of greatest importance in maintaining pregnancy
After 7 weeks the placenta becomes the dominate place for steroid production

Embryology

Embryonic period is the first 49 days after conception- organogenesis is complete at this time

Effects of Teratogens

1. Susceptibility to a teratogen depends on the genotype of the conceptus and on the manner
in which the genotype interacts with the environmental factors.
2. Susceptibility varies with the developmental stage at the time of exposure.
a. Week 2-8 is when most structural defects occur.
3. Teratogens act by different mechanisms
a. Alter normal cellular or biochemical
processes.

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Maternal Physiologic Changes of Pregnancy

1. Cardiovascular System
a. Earliest and most dramatic changes
b. Changes are to improve the festal oxygenation and nutrition
c. Anatomic Changes
i. Heart is displaced upward and to the left
ii. Assumes more horizontal position
1. Result of diaphragmatic elevation from displacement of
abdominal viscera by expanding uterus
iii. Ventricular mass increases
iv. Left ventricle and atrium increases in size parallel with an increase in
circulating blood volume
d. Functional Changes
i. Primary functional change in CV system during pregnancy is increase in
cardiac output (CO)
1. Overall CO increases 30-50%
a. 50% of this increase occurs by 8 weeks
b. Relative reduction in blood flow to splanchnic and skeletal
muscle- absolute amount remains the same
c. 20% of CO to the uterus at term
i. 750cc/min to the uterus at term
2. First half of pregnancy
a. Increase in stroke volume leads to increase in cardiac output
b. Change in stroke volume due to alterations in circulating blood
volume (peak increase at 32 weeks) and systemic vascular
resistance
i. SVR decreases because progesterone increases
ii. This will decrease smooth muscle tone and AV shunting
to the uteroplacental circulation and increase
vasodilatory substances (progesterone, nitrous oxide, and
atrial naturietic peptide).
3. Second half of pregnancy
a. Increase HR and SV returns to normal leading to increase
cardiac output.
ii. Blood pressure
1. Decreased through the second trimester and then normalizes toward
the end of pregnancy
iii. Pulse
1. Resting pulse increases throughout pregnancy
e. Physical Findings
i. Increase in the second heart sound split with inspiration distended neck veins
ii. Low grade systolic ejection murmurs
f. Symptoms
i. Some women have dizziness and syncope
2. Respiratory System
a. Primarily mediated by progesterone
b. Changes occur due to the increase in oxygen demand of the mother and fetus.
c. Anatomic Changes

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i. Elevation of diaphragm- 4cm
ii. Chest diameter and circumference increase
d. Functional Changes
i. Increase in total body oxygen consumption
1. Gravid uterus
2. Respiratory muscles
3. Heart and kidneys
4. Mammary tissue
ii. Elevated diaphragm
1. Decrease in residual volume
2. Decrease in functional residual volume
3. Decrease in total lung volume
4. Increase in tidal volume
5. Increase in inspiratory capacity and minute ventilation
a. Leading to increased ventilation and decreased PCO2
i. Leading to a respiratory alkalosis
b. Respiratory alkalosis is compensated by increased excretion
of bicarbonate via the kidneys
i. Maintains normal maternal arterial pH
e. Physical Findings – no change
f. Symptoms – Dyspnea
2. Hematologic System
a. Increase in plasma volume-(50% increase)
b. Increase in red cell volume
c. Increase in coagulation factors
d. The increase in the oxygen delivery to the lungs and the amount of hemoglobin in the
blood leads to a significant increase in total oxygen carrying capacity

Lungs Placenta
Increased hemoglobin affinity for O2 Increased CO2 gradient between fetus and
mother allows for transfer of CO2 from fetus to
the mother
e. Symptoms- edema
f. Physiologic anemia- the increase in plasma volume is more than the increase in red
cell volume which leads to a normal anemia associated with pregnancy.

Placental Physiology

Three key functions of the placenta

1. Respiratory exchange
a. All gases cross placenta via simple diffusion
b. Dependent on blood carrying capacity of the mother and fetus
c. Uterine and umbilical blood flow
2. Metabolite exchange
a. Glucose is the single primary metabolic substrate for placental metabolism
b. Facilitated diffusion
c. Other solutes dependent on concentration gradient, degree of ionization, size and
lipid solubility

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3. Hormone production
a. Estrogen
b. Progesterone
c. Human chorionic gonadotropin
d. Human placental lactogen

Fetal Circulation

Oxygenation of fetal blood occurs in the placenta

Oxygenated blood is carried by the umbilical vein to the portal system

50% of the blood flows through the ductus venosus to the left ventricle via the foramen ovale

Blood from the proximal aorta supplies the brain and upper body

Blood from the distal aorta supplies the lower body and the umbilical
arteries This blood is deoxygenated and returns to the placenta

(See next page for diagram)

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PART 2 - NORMAL PREGNANCY – PRENATAL CARE and LABOR: PART 2 (19 minutes)

Initial Visit

1. Diagnosis of Pregnancy
a. History
i. Amenorrhea
ii. Fatigue, nausea, vomiting, breast tenderness
b. Physical
i. Enlarged, softened uterus
ii. Chadwick’s sign- bluish discoloration of vagina and cervix
iii. Hegar’s sign- softening of the cervix
iv. Fetal heart tones detectable at 12 weeks by doppler
c. Laboratory
i. urine pregnancy test- measures HCG
1. HCG shares alpha subunit with LH- test must differentiate
2. Tests for beta subunit of HCG
3. Will be positive by 4 wks- best on early morning urine- highest
concentration
ii. Serum pregnancy test- measures HCG
1. More sensitive and specific than urine
2. Can get a quantitative result
iii. Ultrasound
1. Transvaginal- able to see at beta of 1000-2000mIU/mL
2. Transabdominal- able to see at beta HCG of 5000-6000mIU/mL
3. Cardiac activity detectable at >4000MIU/mL
2. Dating
a. Gestational age
i. number of weeks since last period
ii. not conceptual age
b. Naegle’s rule
i. LMP + 7 days – 3 months = Estimated Delivery Date (EDD)
1. First day of the last period is crucial
2. Gestation is 40 +/- 2 weeks
3. Initial Labs
a. Blood type- Rh status is important
b. Antibody screen
c. Complete blood count - Hemoglobin/hematocrit and Platelets
d. Maternal infections or immunity to a number of infections (don’t need to memorize this
list) – Rubella; Hepatitis B surface antigen; Hepatitis C antibody; RPR; HIV; Gonorrhea;
Chlamydia; Varicella
e. Pap (only if indicated at the time of the visit based on current guidelines) for evaluation
of cervical dysplasia / cancer
f. Cystic fibrosis and spinal muscular atrophy (SMA) carrier screening; Hemoglobin
Electrophoresis to look for Sickle Cell trait and other hemoglobinopathies
g. Urinalysis and Urine culture
4. Follow-up visits – you’ll learn these details on your Ob Gyn rotation so don’t worry about this
right now

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Normal Labor

1. Definition- progressive change in a woman’s cervix in the setting of regular, rhythmic uterine
contractions
2. Spontaneous contractions occur throughout pregnancy- most go unperceived
3. Contractions become stronger and more frequent toward term
a. Braxton-Hicks- contractions that are perceived but not associated with cervical change
i. False labor
ii. Typically shorter and less intense than true labor
4. Evaluation of Labor-
b. Historical aspects
i. Contractions every 5 minutes for one hour
ii. Leaking of vaginal fluid
iii. Significant vaginal bleeding
iv. Decreased fetal movement
c. Physical exam
i. Fetal heart tracing
ii. Tocodynamometer- measurement of contractions
iii. Cervical exam
1. Dilation- opening of cervical os
2. Effacement- shortening of cervical canal- expressed as a percentage
3. Station- level of fetal presenting part in the birth canal in relation to the
ischial spines between the pelvic inlet and the pelvic outlet
a. Measured as a 6 or 10 point scale
b. Zero station represents the fetal presenting part at the level of
the ischial spines
c. Positive numbers represent the fetal presenting part below the
level of the ischial spines
d. Negative numbers represent the fetal presenting part above the
level of the ischial spines
iv. Fetal lie- relation of the long axis of the fetus with the maternal long axis
1. Longitudinal
2. Transverse
3. Oblique
v. Presentation- what is the presenting part lowest in the birth canal
1. Vertex
2. Breech
vi. Position- relation of presenting part to the right or left side of maternal pelvis

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Physiology of Labor

Uterine Distension

Mechanical stretch

Gap junction; oxytocin receptor; Prostaglandin

synthase; IL-8

Chorion
+ CRH
Decidu

Proteases Uterotonins

Cervical Change Uterine Contractions

Rupture membranes

Delivery

You will learn about the normal stages of labor, management of labor, and post-partum care in your
Ob-Gyn clerkship.

I have no financial relationships related to this lecture to disclose. – Danielle Cullen, M.D.

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