Fetal and Neonatal Lung Development

Question 1

What are the 5 phases of lung development?

Answer 1

1. embryonic
2. pseudo-glandular
3. canalicular
4. saccular
5. alveolar

Question 2

what is the definition of:
- preterm
- term
- age of viability

Answer 2

preterm:
- less than 37 weeks

term:
- about 40 weeks
- average 38-40 weeks

age of viability:
- time at which a fetus can survive outside the womb based on lung development as all other body systems are developed at this stage (usually with medical intervention)
- about 22 weeks

Question 3

When does the embryonic phase of lung development occur?

Answer 3

3-6 weeks gestation

Question 4

What forms during the embryonic phase of lung development?

Answer 4

1. diverticulum (primitive trachea) on ventral surface of foregut
2. primitive lung buds form (which will give rise to the main bronchi) off the primitive trachea

these both occur through branching morphogenesis

Question 5

What is branching morphogenesis?

Answer 5

growth of undifferentiated respiratory epithelium to form tubes through cellular proliferation

Question 6

What controls branching morphogenesis?

Answer 6

growth and differentiation factors

Question 7

When does the pseudo-glandular phase of lung development occur?

Answer 7

6-16 weeks gestation

Question 8

What occurs at the pseudo-glandular stage?

Answer 8

rapid growth and proliferation of peripheral airways forming the bronchioles and terminal bronchioles
- penetrates further mesenchyme

Mesenchyme now has a loose network of capillaries

Question 9

What type of epithelium is found in the pseudo-glandular phase?

Answer 9

undifferentiated cuboidal or columnar

Question 10

When does the canalicular phase of lung development occur?

Answer 10

16-26 weeks gestation

Question 11

What occurs during the canalicular phase?

Answer 11

further branching into mesenchyme
- mesenchyme becomes more vascularised

respiratory bronchioles are formed

Question 12

What occurs to the epithelium during the canalicular phase?

Answer 12

the cuboidal cells begin to flatten and differentiate into type 1 and type 2 alveolar cells

Question 13

When does the saccular phase of lung development occur?

Answer 13

about 26 weeks gestation until term

Question 14

What occurs in the saccular phase of lung development?

Answer 14

sacs form on the terminal bronchiole which become the alveolar ducts and sacs

the blood air barrier is formed
- occurs through the fusion of capillaries to respiratory epithelium due to mesenchyme thinning

Question 15

What begins being produced by respiratory epithelium during the saccular phase?

Answer 15

surfactant by type 2 cells

Question 16

What is the role of surfactant?

Answer 16

stabilises lungs during expiration by preventing alveolar collapse through lowering surface tensions of water

Question 17

When does the alveolar phase of lung development occur?

Answer 17

32 weeks until after birth

Question 18

What occurs during the alveolar phase?

Answer 18

1. alveolarisation
   - 20-50 mil alveoli develop before birth but mostly immature
   - majority of alveoli are formed after birth
   - sacs form secondary septal crests which arise in walls of alveoli
2. vascularisation
   - vasculature grows in similar pattern to alveoli secondary septal crests

These increase gas exchange capacity

3. increase in number of type 2 cells

Question 19

What is the shape and role of type 1 alveolar epithelial cells?

Answer 19

elongated cells with flat cytoplasmic extensions

large surface area for gas exchange to occur efficiently

Question 20

What is the shape and role of type 2 alveolar epithelial cells?

Answer 20

cuboidal cells with cytoplasmic inclusions (lamellar bodies)

these cells synthesise, store and secrete surfactant

Question 21

Between type 1 and 2 alveolar cells what is the difference between the proportion of each during lung development?

Answer 21

during gestation type 1 cells are up-regulated compared to type 2.

around birth
- type 1 decrease in amount
- type 2 increases in amount until they are both of the same proportion newborn to prepare for breathing

Question 22

What is fetal lung fluid and why is it important?

Answer 22

fetal lung liquid is secreted into developing airways from early gestation
- this provides a distending force (a force that stretched or expands something) to promote normal lung development

Fetal lung liquid has a unique composition (it is not amniotic fluid)

Question 23

How is lung liquid secreted before birth into airway lumen before birth?

Answer 23

Chloride ions move from lung tissue into developing airway lumen

Osmosis occurs to diffuse the chloride ions in lumen (water moves into lumen)

Question 24

How is the lung liquid reabsorbed molecularly out of the lumen of the lung tissue at/after birth?

Why does this occur?

Answer 24

Sodium ions move from lumen into the lung tissue
- this causes water to flow into cells

Stimulated by labour (adrenaline and vasopressin)

Liquid needs to be cleared so baby can breath when born

Question 25

Fetal breathing movements (FBM) are episodic periods of breathing (20-30 m/h). Why are FBMs important for fetus?

Answer 25

when fetus is apneic the lung liquid is trapped in lungs FBM's function is not entirely known but is thought it help tone smooth muscle and develop alveoli.

Question 26

What is the relationship between FBM and intrauterine environment?

Answer 26

FBM/s are sensitive to intrauterine environment (e.g. infection, inflammation, smoking)

Question 27

What is the consequences of reduced lung liquid volume?

Answer 27

Lung hypoplasia (smaller lungs) - can affect one (unilateral) or both (bilateral) lungs This most commonly occurs secondary to another condition

Question 28

Lung hypoplasia commonly occurs secondary to another condition. What are these other conditions?

Answer 28

Reduced amniotic fluid - oligohydramnios - PPROM - fetal renal blockages Space occupying lesions - congenital diaphragmatic hernia

Question 29

Oligohydramnios is an amniotic fluid disorder resulting in decreased amniotic fluid volume for gestational age. There ar acute or chronic forms of this disorder. What is acute oligohydramnios?

Answer 29

Less than 48 hours water breaking - loss of amniotic fluid which allows the fetus to get ready for birth 1. compression of abdominal contents 2. diaphragm needs to move up 3. compression of the lungs which leads to lung liquid loss which is needed for birth

Question 30

Oligohydramnios is an amniotic fluid disorder resulting in decreased amniotic fluid volume for gestational age. There ar acute or chronic forms of this disorder. What is chronic oligohydramnios?

Answer 30

occurs longer than 48 hours 1. compression of abdominal contents 2. diaphragm needs to move up 3. compression of the lungs which leads to lung liquid loss - occurring during non labour time spinal flexion occurs

Question 31

Babies in utero with lung hypoplasia do fine in utero as they do not rely on their lungs for gas exchange. Newborns however are at risk for cardiorespiratory morbidity and mortality, why is this?

Answer 31

1. reduced alveolar number and surface area - thicker inter-alveolar walls leading to less adequate gas exchange 2. less type 1 AEC's - Type 1 are flat allowing for gas exchange - lowering gas exchange capabilities 3. reduction in vasculature branching and vessel number - reducing amount of oxygen getting into blood and an efficient rate - lowering pH levels of blood due to increase in CO2 4. increase respiratory support required - lower lung compliance and ventilation efficiency 5. altered haemodynamics - lower blood flow to lungs - increase blood flow to brain

Question 32

What are the differences between pre-term lungs vs term lungs

Answer 32

pre-term - minimal airway branching and volume for gas exchange within poorly developed alveoli - thick inter-alveolar septa (impaired oxygen transfer) - fewer differentiated type 2 AEC's (lowered surfactant) - lowered surfactant production and secretion to assist in transition to air breathing at birth

Question 33

Respiratory distress syndrome (RDS) is the leading cause of morbidity and mortality in preterm infants (less than 37 weeks gestation). What is the cause of RDS?

Answer 33

reduced surfactant and immature lung structure The reduced surfactant leads to collapsed alveoli persistence of RDS can progress to severe respiratory distress and pulmonary hypotension - increases mortality

Question 34

In fetus: 1. placenta provides oxygen 2. liquid filled lungs help normal growth 3. high pulmonary vascular resistance 4. low pulmonary blood flow (10% of cardiac output) How these change in the fetus's transition to a newborn?

Answer 34

1. lungs provide oxygen 2. air-filled lungs 3. low pulmonary vascular resistance (vessels opened and dilated) 4. high pulmonary blood flow (100% of cardiac output)

Question 35

How do postural changes before birth help the clearance of airway liquid?

Answer 35

1. uterine contractions 2. amniotic fluid loss (water breaking) 3. increase in spinal flexion Due to fetus being squashed in womb there is liquid loss via nose and mouth

Question 36

How do molecular changes at/after birth help the clearance of airway liquid?

Answer 36

1. reversal of lung secretion back into tissue - mediated by adrenaline (active labour)

Question 37

How does inspiration after birth help the clearance of airway liquid?

Answer 37

inspiration triggers lung aeration to clear large volumes of airway liquid rapidly at birth created tans-pulmonary pressure which moves liquid out of airways into tissue - liquid moves into distal airways when air enters lung - liquid then moved across distal airway wall - liquid is the re-absorbed into pulmonary vasculature and lymphatics (4-6 hours after birth)

Question 38

Historically newborns were given invasive respiratory support at birth i the form of intubation and mechanical ventilation which was associated with risk of lung and brain injury. Clinical practice has moved towards less invasive approaches through: 1. Intermittent positive pressure ventilation (iPPV) 2. Continuous positive airway pressure (CPAP) How do these work?

Answer 38

1. iPPV - artificial breaths delivered 2. CPAP - provides constant pressure to support lung aeration and reduced work of breathing - allowing baby to breath on own This occurs through helping baby gain functional residual capacity

Question 39

How does elevated airway liquid volumes at birth predispose to RD?

Answer 39

Term RD most commonly occurs following delivery by caesarean section No labour leads to no postural change to help clear airway liquid and babies then rely solely on movement of liquid into tissues to allow entry of air - babies at risk of greater airway liquid volume and lung oedema lowering oxygen transfer to blood Elevated airway liquid volumes alters size of alveolar and distribution lung - small/distal airways unable to aerate

Question 40

What is the physiology underpinning respiratory pattern observed in term newborns with RD?

Answer 40

1. greater volume in chest (liquid+air) - increase chest wall expansion - lowered diaphragm curvature (flattening) - causing laboured breathing) 2. lungs siffer and harder to aerate - lower lung compliance - decrease in infants ability to inspire (more effort) 3. Reduced respiratory function - lowered functional residual capacity - decreased gas exchange - increase in liquid re-entry between breaths - expiratory grunts to prevent loss of gas volume increased respiratory rate due to poor oxygenation and lung oedema