Fetal and Neonatal Lung Development Flashcards

1
Q

What are the 5 phases of lung development?

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

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

A

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

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3
Q

When does the embryonic phase of lung development occur?

A

3-6 weeks gestation

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4
Q

What forms during the embryonic phase of lung development?

A
  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

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5
Q

What is branching morphogenesis?

A

growth of undifferentiated respiratory epithelium to form tubes through cellular proliferation

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6
Q

What controls branching morphogenesis?

A

growth and differentiation factors

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7
Q

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

A

6-16 weeks gestation

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8
Q

What occurs at the pseudo-glandular stage?

A

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

Mesenchyme now has a loose network of capillaries

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9
Q

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

A

undifferentiated cuboidal or columnar

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10
Q

When does the canalicular phase of lung development occur?

A

16-26 weeks gestation

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11
Q

What occurs during the canalicular phase?

A

further branching into mesenchyme
- mesenchyme becomes more vascularised

respiratory bronchioles are formed

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12
Q

What occurs to the epithelium during the canalicular phase?

A

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

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13
Q

When does the saccular phase of lung development occur?

A

about 26 weeks gestation until term

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14
Q

What occurs in the saccular phase of lung development?

A

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

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15
Q

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

A

surfactant by type 2 cells

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16
Q

What is the role of surfactant?

A

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

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17
Q

When does the alveolar phase of lung development occur?

A

32 weeks until after birth

18
Q

What occurs during the alveolar phase?

A
  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

  1. increase in number of type 2 cells
19
Q

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

A

elongated cells with flat cytoplasmic extensions

large surface area for gas exchange to occur efficiently

20
Q

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

A

cuboidal cells with cytoplasmic inclusions (lamellar bodies)

these cells synthesise, store and secrete surfactant

21
Q

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

A

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

22
Q

What is fetal lung fluid and why is it important?

A

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)

23
Q

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

A

Chloride ions move from lung tissue into developing airway lumen

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

24
Q

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

Why does this occur?

A

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

25
Q

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

A

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.

26
Q

What is the relationship between FBM and intrauterine environment?

A

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

27
Q

What is the consequences of reduced lung liquid volume?

A

Lung hypoplasia (smaller lungs)
- can affect one (unilateral) or both (bilateral) lungs

This most commonly occurs secondary to another condition

28
Q

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

A

Reduced amniotic fluid
- oligohydramnios
- PPROM
- fetal renal blockages

Space occupying lesions
- congenital diaphragmatic hernia

29
Q

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?

A

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
30
Q

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?

A

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
31
Q

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?

A
  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
32
Q

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

A

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

33
Q

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?

A

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

34
Q

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?

A
  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)
35
Q

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

A
  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

36
Q

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

A
  1. reversal of lung secretion back into tissue
    - mediated by adrenaline (active labour)
37
Q

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

A

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)
38
Q

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?

A
  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

39
Q

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

A

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

40
Q

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

A
  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