Lecture 10: Lung development and surfactant

Question 1

What are the basic embryology origins of the lung tissues?

Answer 1

• Lungs are primarily endodermal in origin

- Parenchyma and pleura are mesodermal

Question 2

Describe the periods of the lung development;

Answer 2

Embryonic period (26 days to 7 weeks)
Psuedoglandular period (5-17 weeks)
Cannicular period (16-25 weeks)
Saccular stage (24 weeks to after birth)
Alveolar period (late feotal to 21 years)

Question 3

Describe what happens in the embryonic period;

Answer 3

• Lung bud arises as VENTRAL outpouching of the foregut endoderm
• Initial 3 rounds of branching produces:
  = Primordia of two lungs (primary bronchi)
  = Lung lobes (Lobar bronchi)
  = Bronchopulmonary segments (segmental bronchi)

Question 4

Describe what happens in the psuedoglandular period:

Answer 4

Branching forms:

• Bronchi
• Bronchioles
• Terminal bronchioles

(Only conducting zone formed), looks like glands

Question 5

Describe what happens is the cannicular period:

Answer 5

• Each terminal bronchiole gives rise to two or more respiratory bronchioles
• Each divides into 3-6 alveolar ducts lined by cuboidal cells.

Primitive resp. zone developed

Question 6

Describe the saccular stage:

Answer 6

Alveolar ducts give rise to primitive alveoli

AT1 and AT2
- Surfactant starts to be produced

Question 7

Describe the alveolar stage:

Answer 7

• Increasing n. terminal sacs
• Alveoli mature
• AT1 continue to thin

Question 8

Whats the risk of the embryonic / psuedoglandular stage?

Answer 8

Potential for tracheal / oesophogeal separation defects

Question 9

Describe the in-utero changes to the lungs;

Answer 9

Heart - Ductus arterosus and foramen ovale

= No O2 exchange

Question 10

Describe the changes to the lungs at birth:

Answer 10

During birth - Compression of chest wall expells fluid from lungs +/- fluid re-absorption in lymphatics

• UC clamped, closure of DA and FO
• Inflation of lungs = Dec resistance of pulm. circuits
• Established of air:liquid interface

Question 11

Why is surfactant necessary for reducing surface tension?

Answer 11

Surface tension needs to be lowered because:
- If the surface of the lung was plasma not surfactant, the pressure required to maintain lung volume would be 28cm water rather than 5cm water

Question 12

Describe the constituents of surfactant:

Answer 12

95% phospholipid (polar head, non-polar tail)

5% protein

Question 13

What are the surfactant proteins and structure;

Answer 13

SP-A (Large hydrophilic)
SP-B (small lipophilic)
SP-C (small lipophilic)
SP-D (Large hydrophilic)

Question 14

What is the function of SP-A in surfactant?

Answer 14

• Surface tension reduction
• Host defence
• Regulation of surfactant synthesis

Question 15

What is the function of SP-B in surfactant?

Answer 15

• Formation of tubular myelin

- Formation and stabilisation of phospholipid monolayer

Question 16

What is the function of SP-C surfactant?

Answer 16

• Formation and stabilisation of the phospholipid monolayer

Question 17

What is the function of SP-D surfactant?

Answer 17

• Regulation of surfactant synthesis

- Hose defence (Does not exhibit SPA’s effect on dynamic surface tension)

Question 18

Describe the turnover of surfactant?

Answer 18

Degradation and catabolism (phospholipid turnover 3-11hrs)

• Taken up by AT2 or transported towards ciliated airways
• Degraded by extracellular enzymatic activity
• Macrophage phagocytosis
• Epithelial reabsorption into either lymph or blood

Question 19

Describe the effect of pulmonary surfactant on surface tension:

Answer 19

Reduces surface tension from 70mNm to 10mNm

Creates the PV hysteresis

Question 20

What does pulmonary surfactant do?

Answer 20

Reduces the tendancy for fluid to be sucked into the airspace (i.e from ECM)

Question 21

How does surfactant influence hose defence?

Answer 21

Movement of particular matter towards ciliated regions is aided by surface tension gradients i.e (low in alveoli and higher in airways)

Both SP-A and SP-D act to bind pathogens to promote the action of macrophages in the immune response

Question 22

What are the functions of pulmonary surfactant?

Answer 22

• Improves pulmonary compliance
• Aids fluids balance (removes from airspace)
• Host defence

Others:

• Reduces formation and maintenance of airway plugs
• Reduction of adhesion
• Aids in the hydration and rheology mucus

Question 23

What is NRDS?

Answer 23

Neonatal resp. distress syndrome

• Lack of lung development i.e surfactant or airway development