Lung Development

Lung Development


LUNG DEVELOPMENT
• Embryonic - 3-8 weeks (3-6)

• vascular connection with right atrium
• bronchi develop

• Pseudoglandular 5-17 weeks (6-16)

• peritoneal cavities close
• continued branching
• smooth muscle develops
• terminal buds
• vascularization

• Canalicular 16-26 weeks (16-26)

• capillaries close to alveoli
• surfactant produced
• survival possible at end of this stage
• complex histo

• Saccular 24-37 weeks (26-36)

• first true alveoli
• type I cells flatten = thin
• complex histo
• more surfactant

• Alveolar 36 weeks – 3 years+

• septation of alveli
• 85% of alveoli form postnatally

Airway Development

• 4wk Primitive epithelial cells
• 8wk Neuroendocrine cells appear
• mitogenic
• 10-12wk Presecretory and preciliated 
• 14wk Ciliated cells, neuroepithelial bodies
• mosh pit - move particle to upper airways
• 16wk Goblet (make mucus), serous, basal
• 20-22wk Pre-clara
• 24wk Type I and Type II
• 24-26wk Clara
• detoxify
• regenerate epithelium

Pulmonary circulation

• controlled by VEGF

Bronchial circulation

• branch of aorta

Lymphatic circulation

Barrier Function

• Anatomical-branching
• Ciliated cells
• Mucous cells
• Innate immune function – TOLL-like receptors
• TLRs activated by TGF beta to activate macrophages
• Adaptive immune function

Lung in utero

Pulmonary

• Lung fluid production
• Fluid filled condensed alveoli
• Intermittent fetal breathing movements
• Placenta is the site of gas exchange
• Low PaO2  "Mt. Everest in Utero"

Cardiac

• High pulmonary vascular resistance - collapsed & hypoxic
• Lungs receive 5-10% of cardiac output
• Cardiac circulation shunts past the lung
• Foramen ovale RA-LA
• Ductus venosus - bypass liver
• Ductus arteriosus - bypass lungs

Lungs Post-natally

• Pulmonary
• Lung fluid production stops and fluid is 
• actively resorbed
• Air filled expanded alveoli
• Continuous breathing movements
• Lung is the site of gas exchange
• High PaO2
• Cardiac
• Low pulmonary vascular resistance
• Lungs receive 100% of cardiac output
• Cardiac circulation shunts close
• Foramen ovale closes due to pressure 
• Ductus venosus constricts 
• Ductus arteriosus constricts and obliterate after several days - becomes ligamentum arteriosum

Aging

• Decrease in:
• Static elastic recoil of the lung
• Compliance of the chest wall (but increase
  • in lung compliance)
• – Strength of respiratory muscles
• – Oxygenation (but not carbon dioxide)
• – Respiratory response to hypoxia and
  • hypercapnea

Physical changes in the lung 

with aging

• Cellular-more neutrophils, fewer 
  • macrophages
• Higher elastin/collagen (more lung 
  • compliance)
• Spinal osteoporosis with loss of 
  • height and decrease in lung volume
• Airspace enlargement (senile 
  • emphysema)

Abnormalities of Prenatal 

Lung Growth

• Embryonic-Tracheoesophageal Fistula
• Pseudoglandular-Congenital Diaphragmatic Hernia
• • intestines into thorax = lung hypoplasia
• Canalicular-Pulmonary hypoplasia, 
  • Surfactant deficient lung disease of 
  • prematurity
• • amnioyic fluid = urine
• • IRDS
• • don't have adequate surfactant

• babies are obligate nose breathers

Clinical Signs of Respiratory 

Distress Syndrome

• Grunting
• Flaring
• Retracting
• Increased respiratory rate 
  • to increase minute 
  • ventilation

Chronic Lung Diseases

Bronchopulmonary Dysplasia (BPD)

• after IRDS
• Defined as oxygen requirement at 28 
• days or 36 weeks

Persistent Pulmonary Hypertension

• Right to left shunting at the ductus arteriosis
  • (PDA) and foramen ovale
• Decreased pulmonary blood flow
• Marked hypoxemia