Physiology Or Normal Pregnancy And Fetal Circulation

Question 1

How does hCG levels change with pregnancy

Answer 1

Starts at conception from the fertilized egg granulosa cells

Is usually measured in serum 7 days after fertilization and 14 days after fertilization in urine

peaks in the 1st 8-11 weeks of pregnancy and slowly declines and levels off for the remainder of pregnancy

Question 2

Gestation( menstrual age ) vs ovulation age

Answer 2

Gestation age = time elapsed since the 1st day of the last menstrual period (LMP)
- usually 40 weeks total in pregnancy

Ovulation age = time in days or weeks from ovulation
- usually 38 weeks total in pregnancy

Question 3

What is the time of conception

Answer 3

The term that marks the time in which the sperm travels up though the vagina into the uterus and fertilization of the egg

Question 4

What are the 3 periods of fetal growth?

Answer 4

Implantation = 2 weeks usually

Embryonic period = 7 weeks usually

• is the end of implantation phase -> the beginning of fetal period
• generates all the primordial structures with the neural tube and primitive tube being the 1st two structures

Fetal period = 29 weeks usually

• is the end of embryonic period (9 weeks after last Menses or 7 weeks after fertilization) to birth
• generates all of the actually structures from primordial structures

Question 5

What two tissues is the placenta made up of

Answer 5

Extraembryonic membrane (chorion) of the fetus and endometrial tissues (decidua) of the mother

Question 6

Role of the placenta

Answer 6

To supply the fetus with oxygen and nutrients from the maternal circulation and the decidua of the endometrium, anchors the fetus to the uterus and also acts as an endocrine organ in order to sustain the pregnancy
- the cardiac output from maternal rises 40-50%

Development of the placenta begins with implantation on the functional layer of the endometrium and is matured within 15-20 weeks of gestation

• the cytotrophoblasts erode the spiral arteries fo the endometrium (the main source of uterus vascular resistance in a non-pregnant female). This results in replacement with wide tortuous vessels with high flow rates which increases blood flow to the placenta
• blood pressure in the placenta = 70mmHg

Question 7

Fetal and maternal placenta

Answer 7

Fetal placenta = attached to the fetus by the umblical cord

• carries oxygen poor blood from fetus to the maternal blood supply via the umbilical arteries
• functions as fetal lungs, kidneys, GI tract and liver (thus it has major low-resistance circuit that receives (40%) of fetal blood

chorionic villi contain fetoplacental capillaries which are the primary site of gas exchange between maternal and fetal circulations

Maternal placenta
- provides oxygen rich blood to the fetus via uterine veins

Question 8

How does the placenta exchange gases and nutrients for the fetus?

Answer 8

Most materials cross by simple and facilitated diffusion by concentration gradients
- a small amount does pinocytosis

3 features of the placenta design for optimize transfer

1) minimal nature of the barrier
2) large surface area
3) positioning of the villous trees above maternal blood vessels

COVID seems to be worse in pregnant women, but fetuses dont seem to be effected much

Question 9

Steps in placenta development in days

Answer 9

1) 5-6 days after fertilization = implantation begins and the trophoblast has differentiated into cytotrophoblast and syncytiotrophoblast layers
2) 7-8 days after fertilization = syncytiotrophoblast layer increases in size and invades deeper, surrounding and eroding maternal vessels to form lacunae filled with maternal blood
3) 9-10 days after fertilization = interstitial implantation is close to complete with extension of cytotrophoblasts forming and becoming a covered layer of syncytiotrophoblasts called “primary villi”
4) 11-12 days after fertilization = interstitial implantation is complete extraembryonic mesoderm (amnion and primary yolk sac) has developed from epithelial layers. Also “secondary villi” have formed and ultimately mesoderm will give rise to umbilical blood vessels within the core of the villus to form “tertiary villi”

Question 10

When does implantation actually occur?

Answer 10

Can occur at any stage after fertilization (usually day 7 after fertilization), however the uterus has to be primed with both progesterone and estrogen in order for implantation to actually properly occur

The embryo enters the uterus at around day 3-4 and stays for 3-4 more days and if implantation doesnt occur at this point = death

Question 11

How does the blastocyst obtain nutrients until the placenta is formed? (During first week of implnatation)

Answer 11

Trophoblast that are invading the decidua to generate the placenta digest the decidua cells and provide nutrients for the blastocyst
- this continues for 8 weeks total, but placenta slowly takes over

Placenta usually starts to provide nutrition at day 16 after fertilization

Question 12

Endocrine functions of the fetal placenta

Answer 12

1) hCG
- secreted by the syncytiotrophoblast (fetoplacental precursor) within days of fertilization
- hCG signals the corpus luteum to sustain progesterone and estrogen production
- prevents the uterus shedding and prepare it for implantation
- this continues until the placenta takes over at week 10

2) progesterone
- placenta syncytiotrophoblast and corpus luteum secrete this.
- luteum = prepares the endometrium for implantation
- placenta = reduces myometrial excitability and prevents contractions that could expel the embryo

3) Estrogen
- placenta and corpus luteum generate this (placenta is primary estriol)
- stimulates growth of uterus and breasts

**placenta however by itself has no cholesterol desmolase and 17a-hydroxylase enzymes so it can’t synthesis steroids itself

Question 13

Events of early pregnancy

Answer 13

Based on days after ovulation

1) ovulation = 0 days after ovulation
2) Fertilization = 1 day after ovulation
3) entrance of the blastocyst into the uterine cavity = 4 days after ovulation

4) implantation = 5 days after ovulation
- is critically dependent on low estrogen/progesterone ratio to work
- ** is the period of highest progesterone output
- the endometrium differentiates into decidua cells

5) Formation of trophoblast and attachment to the endometrium = 6 days

6) onset of trophoblast secretion of HCG = 8 days
- without this the corpus luteum with regress 12 days after ovulation which decreases progesterone and intimates menses

7) HCG “rescue” of corpus luteum

Question 14

What is the peptide hormone hPL (human placental lactogen)

Answer 14

Is structurally similar to GH and is secreted by the placenta

Helps to coordinate fuel economy in the fetoplacental unit via converse of glucose to fatty acids and ketones.

Question 15

How does steroid synthesis in the fetus system work

Answer 15

Progesterone steps

1) Cholesterol ester -> cholesterol
- ** only step done in the mother

2) Cholesterol -> pregnenolone

3) pregnenolone -> progesterone
* *2-3 is done in the placenta**

Estriol steps

1) Cholesterol ester -> cholesterol
- ** only step done in the mother

2) Cholesterol -> pregnenolone
- done in the placenta

3) pregnenolone is shuttled out of placenta into the fetus adrenal glands where it is converted into DHEA-sulfate and then 16-OH DHEA-sulfate in the fetus adrenal gland and liver respectively
4) 16-OH DHEA-sulfate is shuttled back into the placenta and converted to Estriol and then sent into the mother

Question 16

Cardiovascular changes in pregnancy

Answer 16

Increases cardiac output

• increases to 50% above prepregnancy value
• caused by increased stroke volume and heart rates
• returns to normal 24 hrs postpartum

Decreases in systemic vascular resistance
- decreases by 20% in uncomplicated pregnancy (diastolic decreases more than systolic)

Increased blood volume but physiological anemia

Hypercoagulability states

Presence of supine hypotension

MAP (COx SVR) remains the same roughly dipping on 3% at most

Question 17

Electrocardiography and echocardiogram changes

Answer 17

Electrocardiography
- increases PR and QT intervals

• QRS axis shifts right in 1st trimester but left in the 3rd trimester
• ST depression in precordial and limb leads
• isoelectric T waves precordial and limb leads
• small Q and T wave inversions in lead 3

Echocardiogram

• displacement of heart anteriorly and leftward
• right chambers increased by 20% and left bu 10%
• Eccentric LVH
• valvular regurgitation (tricuspid is most common)

Question 18

Why does femoral and antecubtial venous pressures differ dramatically in pregnancy if the patient lays supine

Answer 18

Compression of the inferior vena cava occurs as early as 13-16 weeks

• this causes an increase in femoral venous pressure by 50% when supine (since the gravid uterus is impinging on it)
• can get as high as 24mmHg

At birth the pressures go back to the same around 10-8 mmHg

this increase in inferior vena cava pressure results in an increase in mean capillary pressure in the lower extremities resulting in net fluid filtration from blood -> interstitum due to the decrease in plasma colloid osmotic pressure resulting in edema!

Question 19

Respiratory changes during pregnancy

Answer 19

Generally has minor effects on it

However it does increase minute ventilation and tidal volume by 45%
- this occurs at the end of the first trimester to compensate for the increase oxygen demand and CO2 production by the fetus

Also decreases lung capacities below

• TLC (5%)
• FRC (20%)
• ERV (20-25%)
• RV (15-20%)

Partial pressure of oxygen in alveoli increases by 5 mmHg

• this decreases in PaCO2 from 40 -> 30 mmHg
• both result in an increase in cardiac output and Basilar atelectasis as well as decreases alveolar dead space

pregnancy usually results in a respiratory alkalosis which results in renal bicarbonate excretion (this in combo with decreases PaCO2 = slight drop in pH but not clinically relevant. This causes a increase in 2,3-BPG which causes a right shift curve

Question 20

Dilutional anemia of pregnancy

Physiological anemia of pregnancy

Answer 20

This is caused by plasma volume expansion which exceeds the increase of RBC mass increase
- this results in hemodilution

The plasma volume increase (50%) occurs due to Na+/H20 retention. The RBC increase (25%) doesnt keep pace with the plasma volume increase

This reduces total O2 capacity but also helps prevent super high Hypercoagulability states

can cause benign murmurs

Question 21

How does the oxygen-hemoglobin curves differ between maternal and neonates fetal system?

Answer 21

Maternal = right shift
- p50 = 30 mmHg

Fetal = left shift
- p50 = 18 mmHg

This difference in partial pressures results in a concentration gradient from maternal -> fetal system

Question 22

Function of fetal ductus venous, foramen ovale and ductus arteriosus

Answer 22

Ductus arteriosus = shuttles blood from pulmonary trunk to the aorta
- Becomes the ligamentum arteriosus

Ductus venous =- shuttles blood from the hepatic vasculature directly into the inferior cava
- becomes the ligamentum venosum

Umbilical arteries = delivers low oxygen blood from the fetus to the placenta
- becomes the medial umbilical ligaments

Umbilical vein = delivers high oxygen blood from placenta to the fetus
- becomes the ligamentum teres

Foramen ovale = delivers blood directly from right atrium -> left atrium
- closes and becomes the intratrial septum

the placenta acts as the fetal lung, not the lungs so there is no reason for the pulmonary vasculature to get blood at this time

Question 23

How does all the fetal shunts close

Answer 23

Ductus arteriosus/venous and foramen ovale
- increase in systemic vascular resistance, decrease in pulmonary vascular resistance, increases in left atrial pressure, decreases in right atrial pressure and increases in PaO2 also causes closer of ductus arteriosus and foramen ovale

Question 24

Patent ductus arteriosus (PDA)

Answer 24

The ductus arteriosus remains open and high BP from the systemic circulation shunts into the pulmonary circulation (left -> right shunt)

• this causes 50% of blood in left atria to flow back into right atria and results in diastolic pressure to fall very low before each heartbeat
• if severe can cause pulmonary HTN and right sided heart failure

is caused by high levels of circulating PGE2 so administration of indomethacin COX inhibitor that’s okay in children) helps close this

Is common in premature and very low birth weights
- causes a machine-like consistent murmur

Question 25

Patent foramen Ovale

Answer 25

Congenial heart lesion affecting 25-30% of general population

This is usually asymptomatic since the high vascular pressure in the left vs the right atria keeps blood from shunting from right -> left since the valve is occluded for the most part

While it is asymptomatic it does increase the risk for stroke, MI and systemic embolism

Question 26

Persistent pulmonary HTN of newborn

Answer 26

Results from PVR remaining high and not decreasing normally at birth

Causes:

• underdevelopment of pulmonary vasculature
• vascular abnormalities
• bacterial infections

If high enough causes right -> left shunting which results in cyanosis, respiratory distress and tachypnea

Treatment = O2 supplementation and inhaled NO to dilate the pulmonary vasculature

Question 27

Tetralogy of Fallot

Answer 27

Most common cause of blue baby at brith

Shows 4 abnormalities at once usually

1) ventricular septal defect
2) overriding aorta
3) pulmonary valve stenosis
4) RVH

**all 4 combine to cause a large right -> left shunt which results sin low oxygenation at birth

Usually treated with BT shunts within weeks of birth

Question 28

Fetal Cardiovascular response to acute hypoxia

Answer 28

Is triggered by a carotid chemo reflex which causes

• bradycardia (vagal influence)
• increases in peripheral vasoconstriction (constrictor hormones released into fetal circulation O2-:NO ratio and interaction determines this)
• more superoxide anion ions causes constriction, more NO ions causes vasodilation
• *in early gestation the high glycogen levels that prevails in cardiac myocytes may protect the heart from acute hypoxia periods**
• these decrease in late gestation