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Functional Aspects of Lung Development


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6 Phases of Lung development:
What weeks?
1. Embryonic
2. Pseudoglandular - wks 4-7
3. Canalicular - wks 16-26
4. Terminal Sac - 26-birth
5. Alveolar - 32-8yrs
6. Postnatal - up to 8-12 yrs
When does the Embryonic phase take place?
Weeks 4-7
What occurs in the embryonic phase?
Respiratory Diverticulum forms and separates from forming esophagus
What separates the Respiratory Diverticulum from the Esophagus?
Tracheoesophageal Septum
What components of the lungs form during the embryonic phase?
Primary, Secondary, and Tertiary bronchi, and a few generations of subsegmental bronchi.
What tissue development is lung devo like during the pseudoglandular phase?
What is the main thing that happens in the Pseudoglandular phase?
Dichotomous branching of bronchi - 20-25 generations
What causes the dichotomous branching during the Pseudoglandular phase?
Epithelial-mesenchymal interactions.
What 2 types of interruptions can occur in the embryonic phase?
1. Anatomic
2. Partitioning
What could an Anatomic interruption result in?
-Lack of lungs
-Less/More lung tissue
What could a Partitioning interruption result in?
Tracheoesophageal Fissure
What causes a Tracheoesophageal fissure?
Inadequete partitioning due to abnormal or insufficient devo of the tracheoesophageal septum.
What occurs in 90% of partitioning defects?
Blind pouch at end of trachea
Why is a tracheoesophageal fissure dangerous?
Because it can cause regurgitation and aspiration pneumonia.
What 2 major events occur in the Canalicular phase?
1. Distal branches of RD associate w/ devlpng capillaries
2. Type I/II Alveolar Cells begin to differentiate
What is the limit of extrauterine survival? Why?
Wks 22-24 - b/c this is when Type II pneumocytes begin to secrete surfactant
What phase of lung devo correlates with wks 22-24?
END of canalicular phase
What is the main thing that happens in the Terminal Sac phase?
Distal branches of bronchial tree dilate into Terminal sacs
i.e., the alveoli come in CONTACT with capillaries.
What are Terminal Sacs?
Primitive alveoli - they become subdivided into Alveoli
What occurs in the Alveolar phase?
Alveoli formation is accelerated and their septal walls thin.
How much alveoli is formed
Pre = about 20%

Post = The rest - majority
What direction does each occur?
-Airway formation
-Airway differentiation
FORMATION is proximal->distal

DIFFERNTN is distal->proximal
What are the physical characteristics of the prenatal lung? (4)
-Fluid filled
-Resp mvmnt is shallow/episodic
-High pulmonary vasc resistance
-Very low flow in pulm vessels
What results from insufficient fluid production in the prenatal lung?
Hypoplastic lungs
At what 3 sites do changes at birth allow breathing to start?
1. Lung
2. Heart
3. Brainstem
What changes occur in the lung at birth?
Fluid is replaced by air
How is fluid in the lungs replaced by air? (3 steps)
1. 1/3 expelled thru mouth
2. Most absorbed by lung vessels
3. 10% absorbed into lymphatics
What major circulatory changes occur for breathing to start?
-Closing of cardiac shunts
-Pulmonary vasc fills w/ blood
What are the 2 cardiac shunts in the fetus?
-Interatrial shunt
-Ductus arteriosus
What condition results from failure of fluid removal from the lung at birth?
Wet lung
What Neural changes at birth allow breathing to start?
-Continuous resp movements
-Activation of Sympathetic Stimulation decreases secretory activity of lung epithelium
Why is decreased secretory activity of the lungs good at birth?
It allows the newly aerated lungs to not be refilled w/ fluid.
What 3 sites contribute to fluid in the prenatal lung?
1. Amniotic fluid
2. Tracheal glands
3. Lung itself
Through what 3 sites is lung fluid removed at birth?
1. Mouth (1/3)
2. Circulation (Majority)
3. Lymphatics (10%)
Characteristics of the Alveoli air/liquid interface:
-Thin/compliant alveolar wall allows gas exchange
-Surface tension decreases surface area of alveolus
How is surface area TENSION decreased in alveoli?
Via surfactant
What produces surfactant?
Type II Pneumocytes
When is surfactant produced at its peak in the prenatal infant?
35 weeks - surge in synthetic activity
What does Surfactant accomplish?
-Decreased surface tension
-Increased surface area
-Stablized alveolar surface
-Decreased fluid transfer btwn vasculature/alveolar surface
What is pulmonary surfactant made up of?
-Phospholipid 80-90%
-Protein 10%
What 2 phospholipids contribute to surfactant?
Phosphatidylcholine (lecithin)
What is the major disease caused by abnormality in lung devolopment?
Respiratory Distress syndrome
7 clinical signs of RDS:
-Rapid breathing >60 breaths/min
-Flaring nostrils
-Subcostal chest retractions
-Expiratory grunt
-Cyanotic (blue)
-Rapid heart rate
-Anxious facial expression
What are the 3 infants most at risk for RDS?
-Preemies before 37 wks or below 1-1.5 kg
-Babies w/ uncontrolled diabetic moms
Why are males prone to RDS more than females?
Androgens are inhibitory to alveolar maturity
When does RDS become apparent?
24-48 hrs after birth
How is RDS treated?
What is an interchangeable term for RDS?
Hyaline Membrane Disease (HMD)
What are the 5 steps in the typical formation of hyaline membrane?
1. Injury to Type I cells
2. Breakdown of air/capillary interface
3. Leakage of serum into the alveolar lumen
4. Formation of a hyaline membrane
5. Disruption of surfactant
What are the implications of hyaline membrane formation?
The alveoli have decreased surface tension; so more work is required to inflate them at EVERY breath.
How does Surfactant insufficiency manifest physiologically?
-Poor lung compliance
-Atelactasis (alveoli collapse)
-Engorged pulmonary circulatn
-Hyaline membrane
2 Tests for detecting Pulmonary Surfactant Insufficiency:
Which is more accurate?
-L/S ratio
-Phosphatidylglycerol - more accurate
Principle of L/S ratio test:
Sphingomyelin is constant
Lecithin should jump at 35 wks when surfactant production increases.
What does each L/S ratio mean?
>2 means 98% probably OK
1.5-2 means 50% chance RDS
<1.5 likely to have RDS (73%)
What will enhance fetal lung maturation? (treatment if L/S ratio prior to delivery is low)
Who is glucocorticoid administered to then? When?
-24 to 34 wks gestation optimal
-24-48 hrs before birth
Partitioning defects in lung devo can occur up to what stage?
Pseudoglandular - when the last 20-25 branches of the bronchial tree grow.
What anomalies are included in the classification "Partitioning defects"?
-Tracheoesophageal fistula
-Lack of lung
-Extra lung
How are the Canalicular and Terminal Sac periods different?
Terminal Sac starts extrauterine viabilty b/c the capillaries are not only ASSOCIATED w/ alveolar cells, but in CONTACT.
What is the ACTUAL limit of extrauterine viability?
22-26 weeks - at the END of the canalicular phase
What is a much better time to be born prematurely?
35 weeks - b/c Type II pneumocyte production greatly increases at that time
What is tracheoesophageal fistula usually associated with?
Esophageal atresia

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