1. Development of Lung Seoul National University Hospital
Department of Thoracic & Cardiovascular Surgery

2. Lung Unit
Acinus : That part of the lung supplied by a terminal bronchiolus
This includes respiratory bronchioli, alveolar ducts, and
alveoli. It is the respiratory region of the lung.
Lobule : The three to five terminal brochioli, with the acini they
supply, that cluster at the end of any pathway.
Bronchopulmonary segment : Each segment is supplied
by its own bronchus and artery, and draining to veins
that run at its periphery in intersegmental plane.

3. Laws of Lung Development (Reid 1967a, Hoslop and Reid 1974a)
The heart tube is formed by the end of 3 weeks of gestation,
and 5 days later the lung primordia (bud) develops at the
caudal end of laryngotracheal sulcus.
Lobar bronchus of each lung develop at the 5 weeks of gestation.
Bronchial tree is developed by the 16th week of intrauterine life.
During early fetal life, main feature of arterial growth is an increase
in number of branches, whereas during late growth in size & length.
Alveoli develop mainly after birth, increasing in number until
the age of 8 years and in size until growth of chest wall finishes
with adulthood.
The preacinal vessels follow the development of the airways,
the intraacinar that of the alveoli.
Muscularization of intraacinar arteries does not keep pace with
the appearance of new arteries.

4. Preacinal Development of Pulmonary Arteries & Veins
5 to 16 weeks’ gestation
1. Arteries
* The arteries develop as the airway.
* The supernumerary arteries appear at the same time as adjacent
conventional arteries.
2. Veins
* The venous pathways develop at the same time as the arteries.
Changes after 16 weeks
1. Preacinar region
* During late fetal life : The proximal part increases in diameter faster.
* After Birth : They increases at the same rate during infancy and in the
intraacinar vessels, there is greater increase proximally.
2. Conventional & supernumerary arteries
* Both increase in size and each shows a linear relationship to age
* During childhood both increase same rate. (rapid in the first 18 months)

5. Intraacinar Development of Pulmonary Arteries & Veins
A. Branching patterns
1. Before 16 weeks of gestation
* No alveoli are present.
2. After 16 weeks of gestation
* Airways develop beyond the terminal bronchiolus (respiratory bronchiole,
sacules)
* Both conventional , and supernumerary artery appear.
3. After Birth (during childhood)
* As new alveolar duct & alveoli appear and enlarge additional arteries form.
* Few new conventional vessel appear, but supernumeraries increase
considerably.
B. Vessel numbers
1. 1st 3 years of life
* Both arteries and alveoli per unit area increase in number.
2. After 5 years
* The arterial concentration decrease, but since the alveoli have increased
in size, the ratio stay the same.

6. Structures of Pulmonary Arteries & Veins
A. Main pulmonary artery
* During fetal life : resembles the aorta both in its thickness and
configuration of elastic fibrils, (parallel, compact, and uniform in
thickness)
* These features up to about 6 months of age, when changes, starting at birth
* By the 2 years : the adult configuration (40~70% as thick as that of aorta)
B. Intrapulmonary arteries
* During fetal life : The large intrapulmonary arteries have the same structure
as the main pulmonary artery.
* Progressing peripherally along the arterial pathway, elastic lamina
decrease, replaced by a muscular structure, and the elastic laminae
further decrease until in the small arteries.
* Along any pathway the wholly muscular wall get thinner and eventually
the incomplete around the circumference and present only as a spiral.

7. Pulmonary Vascular Development
Arterial size : increase most rapidly during first 2 months of life,
but growth rate remained during first 4 years.
Arterial number : increase most rapidly in the first 2 months,
but subsequent multiplication at same rate as alveoli.
Arterial medial thickness : fall quickly during first several days
(3 days to 2 week) and continue to decrease. (adult level :
4-10 months)
Intraacinal artery becomes more muscular during childhood as
they increase in size. (adult level : 19 years of age)

8. Changes of Pulmonary Vascular Resistance after Birth
1. During fetal life : high resistance in the pulmonary arteries
(constriction of their relatively muscular wall)
2. At birth
* The flow to the lung increases as pulmonary vascular resistance falls.
Dawes (1953) : due to lung expansion
Adams (1966) : neurohumoral control
Heymann (1969) : a mediator (bradykinin) released by 02
3. Immediate fall to half systemic pressure within 3 days
4. Levels near those of adult are reached by 3~6 weeks (Stabilization).
5. Final adult value at 6 months (Growth)

9. Pulmonary Hypertension in Neonate
Pulmonary venous hypertension
Pulmonary venous, left atrial, or mitral obstruction
Left ventricular failure secondary to congenital heart disease
Transient left ventricular dysfunction
Functional obstruction of pulmonary vascular bed
Hyperviscosity
Pulmonary vascular constriction
Persistence of the fetal circulation syndrome (PFC)
Associated with pulmonary parenchymal disease
Premature ductal closure
Decreased pulmonary vascular bed
Pulmonary hypoplasia
Increased pulmonary blood flow
Systemic right ventricle or single ventricle without pulmonary stenosis
Peripheral A-V fistula

10. Etiology of Pulmonary Vascular Disease in CHD
Increased pulmonary blood flow
Increased pulmonary artery pressure
Increased pulmonary venous pressure
Polycythemia(microthrombi)
Hypoxia
Acidemia
Nature of bronchial collateral circulation
Genetic influence

11. Pulmonary Circulation in CHD
The structural response to pulmonary hypertension arising
early in postnatal life
* Many CHD in prenatal period, pulmonary circulation is normal
functionally, structurally.
* At any age especially after 1st week of life, pulmonary hypertension
stimulate hypertrophy of medial smooth muscle cells and the
muscle coat thickness.
* In immature lung with pulmonary hypertension, muscle extends
further along the arterial pathway.
Reversibility of pulmonary vascular disease
* In infancy, high fixed resistance is likely to be due to failure of
intraacinar pulmonary artery to grow and multiply.
* In adult or older children is associated with Grade IV to VI
pulmonary vascular disease.

12. 3 Markers in Obliterative PVD (Reid)
Excessive & premature extension of vascular
smooth muscle to intraacinar artery
Failure of preacinar arterial wall thickness to
regress normally
Failure of pulmonary artery to grow &
proliferate normally with advancing age

13. Sequential Effects of Pulmonary Hypertension
They adapt more slowly, do not adapt completely
to extra-uterine life and then develop additional
smooth muscle.
They fail to achieve a normal increase in number
and size
They develop obliterative pulmonary vascular disease.

14. Outcome of Surgery with Pulmonary Hypertension
Preoperative pulmonary vascular structure
The effect of cardiopulmonary bypass
Immediate postoperative pulmonary hypertension
The reversibility of pulmonary vascular disease

15. Effects of Hypoperfusion on Pulmonary Circulation
Decrease in the development of elastin on proximal elastic
arteries
Decrease in the size and thin muscle coat on intraacinar
Increased pulmonary arterial thrombi causes intimal
fibrosis.
Impaired alveolar development due to hypoperfusion
causes limitation of arterial multiplication.

16. Management of Pulmonary Hypoperfusion in CHD
Establish the presence and size of central pulmonary arteries.
Determine the blood supply of each bronchopulmonary
segment and the size of the intrapulmonary arteries.
Maintain the normal pulmonary arteries and the position and
severity of any stenosis.
Maintain the normal pulmonary arterial pressure within the lung
distal to any stenoses.

17. Adrenomedulin 1. A peptide initially isolated from adrenal medulla,
but in organs such as the heart, lungs, and kidneys
2. Synthesized and secreted by the endothelial cells
and smooth muscle cells of pulmonary vasculature
3. Potent vasodilator effect in the vascular beds of
various organs such as heart, brain, and kidneys
4. Impaired ability to synthesize or secrete ADM in
the pulmonary circulation contribute development
of pulmonary hypertension.

18. Adrenomedulin 1. Adrenomedulin is potent vasodilator peptide and major
effects on cardiovascular function
2. Biosynthesized in a wide variety of organ and cells,
and vascular endothelial and smooth muscle cells also
actively secrete
3. Multiple biologic effects involved in cardiovascular homeostais
4. Strong & long-lasting vasoactive peptide