Development of the Lungs Flashcards
What structures make up the upper respiratory tract?
nasal cavitites
nasopharynx
oropharynx
larynx
Which structures make up the lower respiratory tract?
trachea bronchi bronchioles terminal bronchioles respiratory bronchioles alveolar ducts alveolar sacs alveoli
Which structures make up the conducting portion?
nasal cavities nasopharynx oropharynx larynx trachea bronchi bronchioles terminal bronchioles
Which structures make up the respiratory portion?
respiratory bronchioles
alveolar ducts
alveolar sacs
alveoli
Where is the first location where gas exchange can occur?
The respiratory bronchioles
This is not very efficient and is insufficient to sustain adult life
From which germ cell layers do the lungs develop?
The inner epithelial lining develops from the endoderm
The connective structures and vascular tissue are derived from the mesoderm
What is visible in a 4 week old embryo?
The yolk sac and somites are visible
What regions is the gut tube split into?
- foregut
- midgut
- hindgut
Where is the hindgut located?
It is anything below the Vitelline duct
What is the purpose of the Vitelline duct?
It connects the gut tube to the yolk sac
What is the respiratory diverticulum?
A growth from the gut tube which appears in the ventral wall of the foregut
When does the respiratory diverticulum start to develop?
It appears and starts to develop on day 22
In which direction does the respiratory diverticulum grow?
Ventrocaudally
forwards and towards the thoracic cavity
On day 22, how does the oesophagus exist and how is the respiratory diverticulum formed?
The developing oesophagus exists as just the gut tube
Ventral outpouching from the gut tube forms the respiratory diverticulum
How is the respiratory diverticulum separated from the foregut?
Tracheoesophageal ridges which eventually fuse to form a septum
The trachea then completely separates from the oesophagus
Where do the tracheoesophageal ridges not separate the respiratory diverticulum from the foregut?
At the laryngeal inlet
How does the respiratory diverticulum divide?
It will divide to form 2 lung buds
What is a fistula?
An abnormal connection
What is a tracheoesophageal fistula (TOF)?
An abnormal connection between the trachea and the oesophagus
How does a TOF arise?
An incomplete division of the foregut into oesophageal and respiratory portions
How often do TOFs occur?
In 1 in 3000-4500 live births
What is oesophageal atresia?
There is a fistula between the distal part of the oesophagus and the trachea
The proximal part of the oesophagus has failed to form completely leading to a blind-ended sac
What does atresia mean?
It describes the failure of a structure to form correctly
What is the “atresia” in oesophageal atresia?
The oesophagus is closed or absent
What % of TOFs show oesophageal atresia?
85 - 90%
What are the other 2 main types of TOF?
Oesophageal atresia without the abnormal connection between the oesophagus and trachea
There is no connection at all between the oesophagus and trachea
Fistula between the oesophagus and trachea without the oesophageal atresia
What % of TOFs show the other 2 main types?
Each type accounts for 4% of cases
What is the main symptom of oesophageal atresia associated with the fistula?
The abdomen rapidly distends as the stomach fills with air
The abnormal connection means some air enters the oesophagus which leads to the stomach
What is the main symptom of oesophageal atresia associated with the blind-ended sac?
The blind-ended sac will fill up until the contents of the food enter the respiratory system
No acid is produced in the lungs meaning there is a greater risk of infection
What is a H-type tracheoesophageal fistula?
A fistula that occurs between the trachea and oesophagus
What is the problem associated with a H-type TOF?
Milk is “driven” into the respiratory system
It enters the primary bronchi rather than following the oeosphagus into the stomach
What is meant by VACTERL or VATER associated abnormalities?
These describe a group of congenital malformations which often occur together
What does VACTERL stand for?
V - vertebral defects
A - anal atresia
(C) - cardiac defects
T - tracheoesophageal fistula
E - oesophageal atresia
R - renal abnormalities
(L) - limb defects
What happens around day 28 of development?
the respiratory diverticulum divides into the right and left primary bronchial buds
the oesophagus is partioned from the respiratory diverticulum
What happens during week 5 of development?
Further growth and development results in the formation of secondary (lobular) bronchial buds
How many lobular bronchial buds form?
Why?
3 form on the right side and 2 on the left
The presence of other cells around the bronchial buds determines the amount that will develop
What happens during the 6th week?
Tertiary (segmental) bronchial buds will form
Where are the segmental bronchial buds found and how many of them are there?
They will each supply a bronchopulmonary segment
There are 10 on the right and 8 on the left
When to terminal bronchioles form?
week 16
When do respiratory bronchioles form?
Why is this significant?
week 26
No respiration can occur until these have formed
When do the first alveoli develop?
week 36
How is this process regulated?
The interaction of the epithelium with the overlying visceral mesoderm
The epithelium is derived from the foregut
What structures will form from visceral mesoderm?
cartilage, smooth muscle, connective tissue and capillaries
How does lateral plate mesoderm split?
Splits into visceral mesoderm and parietal mesoderm
how are the pleura formed?
the visceral pleura forms from the visceral mesoderm
the parietal pleura forms from the parietal mesoderm
What is pulmonary agenesis?
the failure of the lung bud to split leading to the complete absence of the bronchi and vasculature
What is the difference between unilateral and bilateral pulmonary agenesis?
Unilateral is survivable as it is the failure to form one of the lungs
Bilateral is incompatible with life as both lungs have failed to form
What is the clinical presentation of pulmonary agenesis in children?
They often develop respiratory distress which compromises lung function
If they acquire a LRT infection, the remaining lung is compromised
What is cyanosis?
Occurs when a baby appears blue due to lack of oxygenation to their tissues
How is pulmonary agenesis related to other congenital anomalies?
60% of children will have other congenital anomalies including cardiac lesions, diaphragmatic hernias and skeletal anomalies
Agenesis of the right lung is associated with higher frequency of anomalies
What are the clinical presentations of pulmonary agenesis in adults?
Progressive breathlessness
Enlarged right lung and deviation of the heart and trachea into the empty space
What is meant by hypoplasia?
It describes when a structure fails to develop to its normal size
What is pulmonary hypoplasia?
All of the components of the lung are present, but they are incompletely developed
What is pulmonary hypoplasia often found in association with?
Congenital diaphragmatic hernia (CDH)
What is a CDH?
The diaphragm fails to form correctly
The intestines and other abdominal structures are pushed into the thoracic cavity
How does CDH usually lead to pulmonary hypoplasia?
The lung does not have enough space to develop so ends up being smaller
What happens if all of the abdominal contents develop in the thorax?
Death as there is not enough space for the heart or lungs to form
What does a change in branching morphogenesis lead to?
Development of supernumerary lobes or segments
What is the extra lobe that often forms?
An azygous lobe which forms due to the branching pattern of the bronchioles
How does branching morphogenesis affect the function of the lungs?
It has no functional significance
What are the 4 periods of lung maturation?
- pseudoglandular
- canalicular
- saccular/terminal sac
- alveolar
What is significant about the maturation periods of the lungs?
They all overlap slightly
When does the pseudoglandular period occur?
between 5 and 17 weeks
What happens during the pseudoglandular period?
Branching of the respiratory tree to form terminal bronchioles
Would a foetus in the pseudoglandular period survive?
No as respiratory bronchioles have not yet developed so respiration is not possible
What other reasons mean respiration cannot occur during the pseudoglandular period?
The capillaries are not close enough to the epithelium for respiration to occur
The epithelium is not yet specialised for gas exhange
When does the canalicular period occur?
between 16 and 25 weeks
What happens during the canalicular period?
terminal bronchioles give rise to respiratory bronchioles, which give rise to alveolar ducts
mesodermal tissue becomes highly vascularised and the capillaries are moving closer to the epithelium
Could a foetus survive during the canalicular period?
There is a low chance of survival
respiration is possible towards the end of this period as some terminal sacs have developed at the ends of respiratory bronchioles
What is the % chance of survival during the canalicular period?
18-20 weeks - 2% chance
25 weeks - 60% chance
When does the terminal sac period occur?
from 26 weeks until birth
What happens during the terminal sac period relating to the epithelium?
The epithelium thins and the capillaries come into close contact with it
This allows for efficient gas exchange as the diffusion distance is short
What is the main thing that happens during the terminal sac period?
Further terminal sacs develop
these are primitive alveoli
What forms during the terminal sac period?
The blood-air barrier
What cells are formed from differentiation of the epithelium during the terminal sac period?
- type I pneumocytes which allow gas exchange to occur
2. type II pneumocytes which secrete surfactant
What is the role of surfactant?
It forms a film over the internal walls of terminal sacs to decrease the surface tension inside the terminal sac
This facilitates inflation
How does surfactant lead to more efficient gas exchange?
It allows for inflation of both the small and large alveoli
This leads to more efficient filling of the alveolar sacs and more efficient gas exchange
Could a foetus born during the terminal sac period survive?
If they are born prematurely (24 weeks) they can survive with intensive care
But they may suffer from respiratory distress syndrome
When does the alveolar period occur?
from 36 weeks until 8 years of age
What happens during the alveolar period?
Increase in the number of respiratory bronchioles and alveoli
More alveoli are developing but they are NOT increasing in size
What % of mature alveoli develop after birth?
95%
When do breathing movements start in the foetus and why?
They start in utero and serve to remove amniotic fluid
This starts to tone the respiratory muscles
What happens to remaining amniotic fluid at birth?
The baby coughs up amniotic fluid and any remaining lung fluid is reabsorbed into the capillaries
What determines whether respiration is possible at birth?
Surfactant must be present in sufficient amounts
What circulatory changes take place at birth and why?
The direction of blood flow is changed
This allows gas exchange to occur at the lungs as oxygenated blood no longer comes from the mother
What is the main factor that determines whether a premature child will survive?
Whether surfactant has been produced in sufficient quantities
(after 26 weeks survival is likely)
What happens if not enough surfactant has been produced?
Collapsed alveolar sacs
When does respiratory distress syndrome occur (RDS)?
When a baby is born prematurely
What happens in RDS?
Laboured breathing threatens the infant with immediate asphyxiation
How is breathing supported in RDS?
There is an increased rate of breathing and mechanical ventilation is often needed to support breathing
What happens to the alveoli in RDS?
The alveolar lining is damaged due to fluid and serum proteins leaking into the alveolus
Continued injury may lead to detachment of the alveolar lining
What can chronic lung injury in preterm infants lead to?
Bronchopulmonary dysplasia
Damage to the lungs caused by mechanical ventilation
What is the treatment for RDS if the mother is susceptible to pre-term birth?
Glucocorticoid treatment
Involves administering steroids to the mother
What does glucocorticoid treatment do?
It accelerates foetal lung development and surfactant production
What is the treatment for RDS after birth?
Surfactant therapy - administering natural or artificial surfactants
More effective with surfactant A and B
What are the roles of surfactant A and B?
A - present where gas exchange occurs
B - involved in organisation of other surfactants
Why is Surfactant Protein B deficiency disease fatal?
Therapy is not sustainable as the surfactant will never be produced throughout life
