L10 Lung Development and Surfactant Flashcards Preview

Respiratory System Module > L10 Lung Development and Surfactant > Flashcards

Flashcards in L10 Lung Development and Surfactant Deck (48):

What is the origin of airways?

primarily ENDOdermal
-epithelial tube lining layer


What is of Mesodermal origin?

Parenchyma and pleura
BV and SM and CT


Mesenchymal and Epithelial transition

complicated signalling process
vice versa/interplay
-happens during lung development


Variation between periods of development

rough stages which overlap
Develop different depending on whether closer or further away from brain


Embryonic period

26days(3/4wk) to 7th week
Ventral Outpouching of Foregut.
form two lung buds --> successive branching
very primitive + limited epithelium
Segmental bronchi formed prior to 7 weeks
Survival: contact w. capillaries thin blood air barrier. no neurdevelopmental areas


Pseudoglandular period

5 to 17 weeks
Mesenchyme. Non-specific structure with tubes pressing into it
-signal driving branching morphogenesis from mesenchyme
-reach Terminal bronchiole (17 generations of branching at 17th week)


Canalicular period

16 to 25th week
1) lung airways (respiratory bronchioles)
2) capillary network (coming into mesenchyme) (capillary invasion working towards epithelium)
25th week- 3-6 primitive alveolar ducts form w. cuboidal cells. beginnning Transitionary area, not bulk but some gas exchange (thick respiratory cuboidal membrane). begin to attenuate
-not many in contact w. thin cells
Survival: possible, but low 20% .have respiratory drive, mechanical diaphragm and intercostal muscles to mechanically drive changes in pressure. no surfactant so increased work of breathing (stop alveolar collapsing)


Saccular / Terminal Sac Period

24th week to after birth
beginning to finish sac formation
Type I associ w. blood and lymph vessels. in contact. (thinning of cells)
Type II pneumocytes appear. limited and begin to produce surfactant
Exponential increase in survival rates


2x critical lung development stages for survival

1. Surfactant
2. Physical ability for gases to exchange from alveoli from blood


Foetal/Alveolar Period

Late Foetal to 8 years
Alveoli formed. Lungs still development
Septisation: Increased interalveolar septa (increase alveoli number) to increase SA
Thinning : until 8 year old. increased demand as more physically active


Formation --> Function of lung development

First 16 weeks : Majority of Formation
Last few branches


Lung Development In Utero

Fluid filled lungs
1) Breathing "practice movement".
2) Hiccups- contractions of diaphraghm
3) Pulmonary vasculatory = High resistance (limited blood going to lungs. just enough to supply development)
4) Rib compressed


Lung Development During Brith

Vaginal Birth
1) Compression: start process of removing fluid


After birth

1) Occlusion of umbilical vein
2) Increased Partial Pressure CO2 (Hypoxic drive)= First Breath
=Huge first breath as has to overcome massive surface tension
=drain fluid away from all airways
1) Inflation of Bronchiole Tree
2) Fluid drains into blood supply and Lymph
3) Reduction in Pulmonary Vascular Resistance
4) Closure of Foramen Ovale
5) Closure of Ductus Arteriosus


Tracheoesophageal Fistula

1 : 3000 Live births
Males (more common)
Blind ending tube of oseophagus (pouch)
-Regurgitation and choking. Fixed surgically.


Variations of Tracheoesophageal Fistula and Rare anomalies of Trachea

Upper segment of oesophagus ending in trachea
Lower segment of variable length
1. double fistula
2. fistula w/o oesophageal atresia
3. oesophageal atresia w/o fistula
4. aplasia of trachea (lethal)
5. stricture of trachea (web/hourglass)
6. Absence of cartilage (inspiration billowing, expiration sucked in)
7. Deformity of cartilage
8. Abnormalities of bifurcation (upper + lower lobes, right + left bronchus)



Phylogeny reflects Ontogeny
Evolution of organ systems is largely effected in developmental embryology


Water Surface Tension

if remove surface tension, the energy of the surface at tension development has gone


Diver's swimming pool bubbles

1. diver can see what they're hitting
2. breaks surface tension, reducing possibility of injury upon entry into water


Necessity of Lower Surface Tension

Need to lower surface tension in lung
otherwise at Tension development, it is too high for the lungs to achieve an adequate amount of work, to overcome the work of breathing


Surface lining and pressure of lung volume

If the surface of the liquid lining of the lung was plasma (71mNm-1 surface tension) (relatively high)
the pressure required to maintain lung volume would be 28cmH2O, rather than 5 cmH2O
-6x higher water-pressure-gradient
-the surface tension/recoil is trying to collapse the alveoli. therefore to maintain alveoli expansion need to create an opposite pressure
Larger than Work to expand and collapse lungs


Pulmonary Surfactant composition

95% Phospholipid
5% Protein (terminal defects if some absent/dont survive)


Pulmonary Surfactant Production

Type II Alveolar Cells
Lamellar Bodies (electron dense structures)
-onion like
-layers= surfactant phospholipids and proteins packed in a highly structured/ordered manner
-similar to cell membranes
-once produced has a mechanism to get out of cells and be distributed around liquid membrane


Pulmonary Surfactant Phospholipids

Fulfil energetic demands
1) 2x Non-polar Tails
=fatty/lipid components. HydroPHOBIC
=carbon chain length (up to 18) (vary in length)
=Derived from glucose and/or glycerol
2) Polar Head
Hydrophilic (actively favour surface enviro)
-Choline, Inositol, serine, Glycerol, Ethanolamine


Pulmonary Surfactant Phospholipid Tail

Fulfil energetic demands
1) 2x Non-polar Tails
=fatty/lipid components. HydroPHOBIC
=carbon chain length (up to 18) (vary in length)
=Derived from glucose and/or glycerol


Pulmonary Surfactant Phospholipid Head

2) Polar Head
Hydrophilic (actively favour surface enviro)
-Choline, Inositol, serine, Glycerol, Ethanolamine
-actively favour the surface environment
-aggregate at the surface, if dont interfere/interact with each other, then reduces its surface tension


Surfactant Protein SP-A

SP-A : Large Hydrophilic (favour aqueous enviro)
Surface tension reduction. Host Defence. Regulation of surfactant synthesis
(non-specific immunological molecules)


Surfactant Protein SP-B

SP-B: Small Lipophilic
Formation of tubular myelin (highly structured) (then needs to be broken up). Formation and stabilisation of the phospholipid monolayer
-important in converting phospholipids from highly ordered membrane-like components --> into useful independant molecules


Surfactant Protein SP-C

SP-C: Small Lipophilic
Formation and (2 secondary to SP-B) Stabilisation of the phospholipid monolayer


Surfactant Protein SP-D

SP-D: Large Hydrophilic
(favour aqueous enviro)
Regulation of surfactant synthesis. Host Defence. (Does not exhibit SPA's effect on dynamic surface tension)
(non-specific immunological molecules)


Where is the production of surfactant proteins?

Synthesis of surfactant proteins occurs primarily in alveolar type II cells


Formation fo Phospholipid Monolayer

Lammelar Body (+ SPA, SPB and Ca2+)
--> Tubular Myelin (fine mesh highly structured) (SP-A, SP-B, SP-C break it up)
--> Phospholipid Monolayer (single layer aggregated at surface)


Phospholipid turnover rate

3-11 hours (phospholipid turnover rate)


Surfactant dysfunction

in Acute conditions
-increased work of breathing due to surfactant dysfunction
-3-11 hours (phospholipid turnover rate)


Degradation and Catabolism

Alveoli are continuously expanding and collapsing
-molecules will bang into eachother
-causes them to degrade over time due to Mechanical disruption
*Taken up by Alveolar type II cells via Endocytosis
*Transport towards ciliated airways (due to surface tension gradient/escalator effect) (low s-t enviro at bottom --> high s.t. enviro)
* Degradation by extracellular enzymatic activity (preoteases in lung, (out of hand can cause lung disease) but also breaks down surfactant proteins)
* Macrophage phagocytosis (1. non-specific immune response binding to pathogens. 2. phagocytosis of independently of surfactant)
*Epithelial reabsorption into either lymph or blood (recirculationg and reuse)


Effect of Pulmonary Surfactant on Surface Tension

Water molecules want to compress together into the smallest possible space
Surfactant b/w interferes with water attraction
Replace water molecules with all surfactant at surface= don't attract each other= no tension = marked reduction in desire of surface to collapse
=easier to expand + easier to keep constant (pressure required to expand and collapse markedly reduced)


What is the Quantitative Effect of Pulmonary Surfactant on Surface Tension

Reduces surface tension from 70mNm-1 --> to 10mNm-1
(6/7x fold reduction in work of breathing and the pressures required to maintain the lung)


Surfactant molecules during breathing

Expand surface= molecules move in
Compress surface= surfactant molecules move out
Energy dependant system (doesnt require as much energy)
-reduce tidal volume = reduced surface area = increased surface tension
sigh: expands lung and facilitates reintroduction of surfactant molecules, and hence reducing surface tension



expands lung and facilitates reintroduction of surfactant molecules, and hence reducing surface tension



The degree to which the lung will distend per unit change in pressure
(the pressure required to expand the lung by any given volume)
CL = delta V / delta Ptp = delta V / delta (Palv -Pip)
Determined by:
1) Elasticity of Lung tissue (tissue recoil in elastic elements)
2) Surface tension of the air liquid interface in the alveoli


Compliance Graph

Inflate lung with Saline: only see extent of elastic recoil in lung tissue. Elastic component only (as have eliminated air-water surface tension)
-steep= less pressure required to largely increase volume
Inflate lung with Air: (combined effect)
-4x more pressure required for same increase in volume
-air-water surface tension is largest components in working regions of lung capacity (high lung capacity is more combined effect)


Law of Laplace

P= (Tu/r1) + (Tu/r2)
For a sphere r1 and r2 are equal.
The thickness of the alveolar wall can be considered negligible.
Thus the equation can be rewritten:


Law of LaPlace w. Bubble

Pressure required to keep same volume of bubble = 2x Tension on wall/radius
Small radius= large tension
= lung has to have small alveoli to be functional (small to increase SA)
=large pressure required to maintain volume (overcome this by reducing tension of lung lining with surfactant)


Fluid Balance

Pulmonary surfactant reduced the tendency for fluid to be "sucked" into the airspace
Negative pressure b/w jar and collapsable lining
=same as negative pressure b/w alveoli and interstitial space
= negative pressure draws fluid into the lung = oedema
high surface tension can cause pulmonary odema (which decreases efficiency of surfactant, positive feed-back loop)


Host defence

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


Reduction of formation and Maintenance of Liquid pegs

Just after birth= small lungs + high fluid content
=have liquid plugs causing no movement of gas into gas exchange regions
(large amounts of liquid form plug)
Surfactant + plug
1. reduces likelihood of plug forming
2. increases likelihood of plugs breaking up


4x Functions of Pulmonary Surfactant

1. Improves pulmonary compliance
2. Aids fluid balance
3. Host Defence
4. Other functions of Pulmonary Surfactant
-reduces the formation and maintenance of liquid plugs
-reduction of adhesion (primarily in upper airways)
-aids in the hydration and rheology mucus


Varying degrees of surfactant dysfunction have been described in:

1. Compliance of Premature:
-alveolar Pneumocyte Type II produced late in pregnancy
-their ability/biosynthesis of surfactant starts late term
2. Infectious Lung Disease (impaired surfactant function. mechanical ventilators) (bigger pic issue)
-HIV (pneumocystis carni pneumonia)
-pulmonary oedema
3. Obstructive Lung diseases
4. Congenital Diseases
-CF Cystic Fibrosis
-Surfactant protein-B deficiency (lethal. can produce phospholipids, but cant transitional function lamellar bodies into functional phospholipid monolayer)
5. Non-specific Respiratory Diseases
-ARDS (Adult Respiratory distress disorder) (trauma, or acute infections. similar conditions to NRDS)