Lecture 10

Question 1

What are the airways germ layer?

Answer 1

Primarily endodermal in origin and the parenchyma and pleura are mesodermal.

Question 2

Describe the lung development stage at 26days to 7 weeks?

Answer 2

EMBRYONIC:
The first starting of the lung development at 3-4th week. It is the ventral out pouching of the foregut/bud that comes form the primitive gut. Primitive trachea, forms two lung buds. Already down to the segmental bronchi. Need contact with the capillaries in order to survive.

Question 3

Describe the lung development stage at 5-17 weeks?

Answer 3

PSUEDOGLANDULAR:
Mesenchyme (non-specific structure) and tubes are pressing into it. Drives the branching morphogenesis - by the mesenchyme. Gone through 17 rounds of branching.

Question 4

Describe the lung development stage at 16-25 weeks?

Answer 4

CANALICULAR:
The lung airways are starting to form in the respiratory zone - respiratory bronchioles and lots of capillaries that are forming in the mesenchyme. The 25th week is a critical point for survival. Starting to get primitive alveolar ducts forming - cuboidal cells. So we will have limited gas exchange. Physically the baby could survive but it would be struggle (10-20% survival rate).

Question 5

Describe the lung development stage at 24 weeks to birth?

Answer 5

SACULAR:
Start to get the development of primitive alveoli. Type 1 cells are intimately associated with blood and lymph capillaries - getting the contact. Type 2 cells develop and begin to produce surfactant. Chance of survival start to increase.

Question 6

Describe the lung development stage at late foetal to 8 years?

Answer 6

FOETAL/ALVEOLAR:
The number of terminal sacs increase. The alveoli continue to get thinner and establish greater contact with capillaries - establish alveolar septa. Increase the septa, so increase the number of alveoli thus increase the SA.

Question 7

What happens in utero?

Answer 7

The foetus doesn’t breathe as the lungs are filled with amniotic fluid. The baby will practice breathing/contraction of the diaphragm. The mother will be abel to feel hiccups. The pulmonary vasculature has high resistance (just enough to supply development).

Question 8

What happens during birth?

Answer 8

During vaginal birth, there is high compression which starts to remove the process of fluid in the baby’s lungs.

Question 9

What happens after birth?

Answer 9

There is occlusion of the umbilical vein. Then there will be an increase in carbon dioxide pressure which will increase respiratory drive (ventilation increase). There will be an increase in inflation of the bronchial tree, and then there will be drainage of blood and lymph. The pulmonary vasculature resistance decreases, and there is closure of the foramen oval and ductus arteriosus.

Question 10

Describe tracheoesophageal fistula?

Answer 10

1 in 3000 live births, more common in males. It is poor development of the out pouching. Most common one is blind ending of oesophagus.

Question 11

Describe surface tension?

Answer 11

Need to lower surface tension in the lung, otherwise it is too high and will increase the work of breathing. If the surface of the liquid lining of the lung was plasma (71mNm-1) the pressure required to maintain lung volume would be 28cmH2O rather than 5cmH2O. This is quite high, thus the work would be higher.

Question 12

What is the makeup of pulmonary surfactant?

Answer 12

95% phospholipid

5% protein. Mixture of these things, need all proteins.

Question 13

What produces surfactant?

Answer 13

Produced in Alveolar Type 2 cells. Have lamellar bodies, the layers in there are the surfactant packaged.

Question 14

Describe pulmonary surfactant phospholipids?

Answer 14

Non-polar tail - does not want to be in an aqueous environment. Up to 18 carbon chain length, derived from glucose and/or glycerol. Hydrophobic.
Polar head - prefers aqueous environment. Choline, inositol, serine, glycerol, ethanolamine.

Question 15

Describe the surfactant proteins?

Answer 15

There are 4 proteins: SP-A, SP-B, SP-C, and SP-D.

Question 16

Describe SP-A protein?

Answer 16

It is a large hydrophilic protein, that reduces surface tension, host defence and is involved int he regulation of surfactant synthesis.

Question 17

Describe SP-B protein?

Answer 17

It is a small lipophilic protein, that is involved in the formation of tubular myelin, the phospholipid monolayer and the stabilisation of the monolayer.

Question 18

Describe SP-C protein?

Answer 18

It is a small lipophilic protein that is involved in the formation and the stabilisation of the phospholipid monolayer.

Question 19

Describe SP-D protein?

Answer 19

It is a large hydrophilic protein that is involved in the regulation of surfactant synthesis. Host defence (does not exhibit SPA’s effect on dynamic surface tension).

Question 20

Describe the formation of phospholipid monolayer?

Answer 20

The lammetlar body is excreted into the surface of the liquid lining of the lung and forms the tubular myelin. Need SP A and B to make the lammetlar body into the tubular myelin. Then SP A and B break it up to form this single monolayer of phospholipids all aggregated at the surface.

Question 21

Describe the degradation and catabolism of phospholipids?

Answer 21

Phospholipids turnover rate is 3-11 hours depending on your age. In acute situations where phospholipid production is impaired, this is one of the things that can cause work of breathing to increase. The phospholipids are taken up by alveolar type 2 cells and are transported up towards the ciliated airways (due to surface tension gradient). Degradation by extracellular enzymatic activity (proteases). Macrophage phagocytosis. Epithelial reabsorption into either lymph or blood.

Question 22

Describe the effect of pulmonary surfactant on surface tension?

Answer 22

Water molecules at the surface are attracted to each other, this is what is producing the tension effect. If you put surfactant molecules within there, it interferes with the water molecule attraction. If all the surfactant is at the surface (they don’t attract each other) then there is no surface tension. There is marked reduction in the desire for a surface to collapse, thus easier to expand and easier to keep pressure constant. Reduces surface tension from 70mNm-1 to 10mNm-1.

Question 23

What happens when you breathe?

Answer 23

As you expand the surface the molecules move in and as you compress the molecules move out. Still requires energy but not that much. Reduction in VT reduces the surface area and squeezes the surfactant out.

Question 24

Describe compliance in terms of surfactant?

Answer 24

Compliance is the degree to which the lung will distend per unit change in pressure. It is determined by the elasticity of the lung and the surface tension of the air liquid interface in the alveoli. When you inflate the lung with saline, you eliminate the surface tension effect - so only see the elastic recoil of the lung (so don’t need that much pressure to increase volume). Where as when you inflate lung with air, you require a greater pressure to change the volume due to surface tension.

Question 25

Describe the Law of Laplace?

Answer 25

For a sphere r1 and r2 are equal. The thickness of the alveolar wall can be considered to be negligible. If radius is small then pressure will be high. Reduce the tension of the lining of the lung will decrease the pressure.

Question 26

Describe the fluid balance function of surfactant?

Answer 26

Surfactant reduces the tendency for fluid to be “sucked” into the airspace.

Question 27

Describe the host defence function of surfactant?

Answer 27

Movement of particulate matter towards ciliated regions is aided by surface tension gradients.
Both SP-A and D act to bind to pathogens to promote the action of macrophages in the immune response.

Question 28

Describe the reduction of formation and maintenance of liquid plugs function of surfactant?

Answer 28

With liquid plugs there is no movement of gas - thus no gas exchange. Surfactant increases the likelihood of the plug breaking up.

Question 29

Describe the varying degrees of surfactant dysfunction?

Answer 29

Premature:
1. NRDS - neonatal respiratory distress syndrome.

Infectious Lung Diseases:

1. Pneumonia.
2. HIV.
3. Pulmonary Oedema.

Obstructive Lung Diseases:

1. Asthma.
2. Bronchiolitis.
3. COPD.

Congenital Diseases:

1. Cystic fibrosis.
2. Surfactant protein-B deficiency.

Non-specific Respiratory Diseases:
1. ARDS.