Fetal physiology & changes at birth

Question 1

What are the shunts present in the fetal circulation?

Answer 1

1. Ductus arteriosus: Between the pulmonary trunk and the descending portion of the arch of aorta. It allows blood from right side of heart to bypass the high resistant pulmonary circulation.
2. Foramen ovale: Between right and left atria. Allows blood to flow straight from right to left atrium as it enters from the IVC.
3. Ductus venosus: Between the umbilical vein and the IVC. Allows blood to bypass the high-resistance hepatic vasculature and enter the IVC.

Question 2

Which side of the fetal heart is dominant?

Answer 2

Right side

Question 3

What is the normal cardiac output for fetal heart and why is is that high?

Answer 3

• ~300 ml/kg/min
• High to maintain adequate blood supply to fetal liver despite 40-50% of CO going to placenta

Question 4

What is the normal heart rate for fetus?

Answer 4

120-180 bpm

Question 5

How does the fetal circulation ensure that the cerebral circulation receives most oxygenated blood?

Answer 5

The foramen ovale allows oxygenated blood from the IVC to pass directly into the left atrium and ventricle. Blood leaving the left ventricle is much better oxygenated compared to blood from the right as it has mixed with the least amount of deoxygenated blood from SVC. It supplies the carotid arteries and thus the brain.

Question 6

What are the sources of amniotic fluid?

Answer 6

1. Kidneys (400-1200 ml/day)
2. Lungs (300-400 ml/day)

Question 7

What factors can influence fetal renal fluid output?

Answer 7

• ADH
• ATII
• Aldosterone
• Prostaglandins

Question 8

What causes increased fetal cortisol production prior to birth?

Answer 8

Maturation of HPA

Question 9

What are the changes to the pulmonary circulation that occur at birth?

Answer 9

1. At birth, expansion of the lungs as the neonate takes its first breath causes decrease in pulmonary vascular resistance.
2. This causes increased pulmonary blood flow (from 35ml/kg/min to 150-200ml/kg/min).

Question 10

What mediates the closure of the foramen ovale at birth?

Answer 10

• Closure of FO is purely physiological, as a result of its one-way valve nature.
• As pulmonary blood flow increases, VR to left atrium increases so that LAP > RAP, resulting in closure of FO.
• Anatomical closure occurs much later in life (or not at all, “probe patent FO”).

Question 11

What mediates closure of the ductus arteriosus at birth?

Answer 11

Closure occurs as a result of decreased concentration of PGE2 and PGI2 possibly due to increased pulmonary blood flow (and enzymes present in pulmonary circulation).

Question 12

What mediates closure of the ductus venosus at birth?

Answer 12

Closure due to collapse caused cessation of blood flow in umbilical vein, which is due to tying off of umbilical cord (passive) and possibly contraction in response to elevated PO2.

Question 13

How is patent ductus arteriosus at birth treated?

Answer 13

COX inhibitors such as indomethacin

Question 14

Why does fetal CO/mass need to be high compared to adult?

Answer 14

1. High contribution to the placenta (~50%)
2. Lower PO₂ in fetal blood

Question 15

What is the consequence of closure of ducts in fetal circulation in terms of its effects on the circuitry of circulation?

Answer 15

• Before birth, the 2 sides of the heart work like pumps in parallel, both pumping blood into the systemic circulation.
• After birth, the 2 sides of the heart work like 2 pumps in series. Right side pumps blood into pulmonary ciruclation while left side pumps blood into systemic ciruculation.

Question 16

What is the nature of fetal breathing movements?

Answer 16

1. These begin 10 weeks into gestation but intensify 2-3 weeks before parturition.
2. Breathing occurs in 1-4 hour period each day, and occurs in ~30 minute episodes coinciding with REM sleep.

Question 17

What are the functions of fetal breathing movements?

Answer 17

1. Helps develop breathing neuromuscular reflexes before birth.
2. Helps development and maturation of the lungs and alveoli.

Question 18

How does the pulmonary epithelium mediate secretion of lung fluid in fetus?

Answer 18

Fluid secretion is driven by Cl^- secretion from the pulmonary epithelium, which also drives passive Na⁺ secretion.

Question 19

How is lung liquid removed during birth?

Answer 19

• About 30% is achieved through mouth by increased intra-thoracic pressure during birth in birth canal
• 70% is taken up by reabsorption (or 100% during c-section).

Question 20

What stimulates change in pulmonary epithelium from fluid secretion to fluid abosrption?

Answer 20

Cortisol and TH

Question 21

How does cortisol stimulate lung fluid absorption at birth?

Answer 21

1. Increased expression of β-adrenoreceptors in the fetal lungs
2. Increased expression of ENaC in fetal lungs
3. Increased expression of PNMT expression in the fetal adrenal medulla and lungs (increased production of adrenaline)
4. Increased activity of deiodinase enzyme and conversion of T₄ to T₃

Question 22

What is the role of cortisol in inducing pulmonary surfactant production?

Answer 22

1. Induces maturation of type II pneumocytes
2. Increases expression of β-adrenocreceptors in the lungs

Question 23

How can IRDS be treated?

Answer 23

1. High pressure artificial ventilation (rarely used as O₂ can cause blindness in neonates)
2. Artificial surfactant
3. Maternal administration of glucocorticoids before birth

Question 24

What are the possible stimuli for first breath in neonate?

Answer 24

1. General arousal (increases sensory inputs)
2. Cold (increased C fibres stimulation)
3. Breaking/tying of umbilical cord (causes hypoxia)
4. Neonate grunting against closed glottis (increases trans-pulmonary pressure and expands lungs)

Question 25

Why is important that the thresholds fetal baroreceptors/chemoreceptors are reset at birth?

Answer 25

- The baroreceptors/chemoreceptors function in the fetus in order to maintain constant blood pressure and blood P_O2. However, in the neonate, blood pressure (due to no more contribution to placenta) and blood P_O2 (due to breathing) increase. - The baroreceptors/chrmoreceptors are set to maintain the fetal BP/P_O2 before birth. - If these thresholds aren’t changed post-birth, the high BP/P_O2 experienced would cause reflex bradycardia and hypoventilation.

Question 26

Why is heat loss a challenge to the neonate?

Answer 26

1. High surface area to volume ratio 2. Increased evaporation heat loss due to being wet after birth 3. Little insulation (hair, subcutaneous fat) 4. Little skeletal muscle for shivering 5. Inability to carry out behavioural responses (e.g. move to hot area)

Question 27

How is thermoregulation achieved in neonate?

Answer 27

Non-shivering thermogenesis (brown adipose tissue)

Question 28

What mediates increased activity of brown adipose tissue in neonate?

Answer 28

Increased brown adipose activity is mediated partly by cortisol before birth, which increases synthesis of T₃, which increases synthesis of UCP1.

Question 29

Why is heat gain a challenge to the neonate?

Answer 29

1. High surface area to volume ratio 2. Underdeveloped sweating mechanism 3. Inability to carry out behavioural responses (e.g. move to cool area)