Development of the Human Lung

	Peter Rothstein, MD
	Professor of Clinical Anesthesiology and Clinical Pediatrics
	(Retired)

Learning Objectives:

	Understand the growth and functional development of the respiratory system
	Identify the stages of lung development and the major events of each stage
	Understand the physical and biochemical requirements for alveolar development and function
	Identify the developmental causes of neonatal respiratory failure, tracheoesophageal fistula and diaphragmatic hernia

Phases of Lung Development

	Lung Growth
		Structural development
		Anatomic development
		Affected by physical factors
	Lung Maturation
		Functional development
		Biochemical development
		Affected by hormonal factors

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Derivation of lung elements

	Lung buds lined by endodermally derived epithelium—differentiates into respiratory epithelium, which lines airways and specialized epithelium that lines the alveoli
	Ectoderm-contributes to innervation
	Mesoderm- blood vessels, smooth muscle, cartilage and other connective tissue

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"The pseudoglandular stage takes place..."

	The pseudoglandular stage takes place between the 7th and 16th week of embryonic development

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"For branching to occur,"

	For branching to occur, bronchial mesoderm is required.
	The rate and extent of branching is proportional to the amount of mesenchyme present.
	After 16 weeks, further growth occurs by branching and elongation.

"Cilia appear in the proximal..."

	Cilia appear in the proximal airways by 13 weeks.
	There is a transition from bronchial epithelial cells (ciliated and columnar cells) to alveolar Type II cells.

"Mesenchyme is necessary for epithelial..."

	Mesenchyme is necessary for epithelial differentiation to occur.
	Differentiation of mesenchyme requires the presence of lung epithelium.

Canalicular Period 16-26 wk

	By 20 weeks the alveolar Type 1 cell is present
	Lamellar bodies start to appear in Type 2 cells

Terminal Sac Period  26 wk →

	Surfactant appears in lamellar bodies of Type 2 cells.
	Stability of the lung at birth correlates with the number of lamellar bodies present.

"By 20 weeks,"

	By 20 weeks, the alveolar Type 1 cell is present.
	Lamellar bodies start to appear in Type 2 cells.

Primitive Saccule

	Approximately 20 x 106 saccules present at birth.

Postnatal stage

	“Adult” configuration reached by 5 weeks.

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Characteristics of Mature Alveolus

	Connected to alveolar duct
	Lined with Type 1 cells, which are in intimate contact with capillaries
	Each capillary is exposed to 2 alveoli
	Contains surfactant
	Has interconnections with adjacent alveoli through pores of Kohn.

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Development of Pulmonary Arterial Muscle

Control of Pulmonary Blood Flow

	Physical Location of Lung Unit
	Gravity
	Oxygen
	Nitric oxide

Hypoxic Pulmonary Vasoconstriction

Physical Influences on Lung Growth

	Lung Liquid

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Physical Influences on Lung Growth

	Amniotic fluid
		Oligohydramnios→Potters syndrome

Physical Influences on Lung Growth

	Congenital diaphragmatic hernia
	Musculoskeletal abnormalities of the chest wall
	Space occupying lesions of the thorax, e.g. pleural effusions
	Oligohydramnios associated with renal or urinary tract abnormalities

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Hormonal Influence on the Lung

	Corticotropin stimulates cortisol
	Cortisol stimulates fetal lung fibroblast to produce fibroblast pneumocyte factor, which,
	Stimulates surfactant production in Type 2 cells
	Thyroid hormone is also necessary for surfactant production

Hormonal Influence on the Lung

	At birth, epinephrine and arginine vasopressin suppress fetal lung fluid production and play a role in its reabsorption

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The Problem of Prematurity

	Birth before 36 weeks may be associated with respiratory compromise and failure.
	80,000 cases/yr of neonatal respiratory failure
	8,500 deaths
	CNS injury in survivors
	Cost = $4.4 billion/yr

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Neonatal Respiratory Failure

	Incidence
		20/1000 boys
		15.6/1000 girls
		29/1000 blacks

The lung is ignored only at your own peril!

DON’T HOLD YOUR BREATH!