HT SEPTEMBER 2012

THE DEVELOPMENT OF
THE LUNG

AN OVERVIEW
HAMIADJI
 THE DEVELOPMENT OF
THE LUNG

• AN OVERVIEW
• HAMIADJI

HT SEPTEMBER 2012
 LECTURE OUTLINE

1. INTRODUCTION
2. EMBRYONIC PHASE
3. PSEUDOGLANDULAR PHASE
4. CANALICULAR PHASE
5. SACCULAR PHASE
6. ALVEOLAR PHASE
7. CLASSIFICATION IN THE ADULT LUNG
INTRODUCTION

The lungs as breathing organs are unnecessary for intrauterine existence. Nevertheless,
they must be developed to such an extent that they are immediately ready to function
following birth. This explains why the entire development extends from the embryonic
period through the fetal period up to birth (and even afterwards).
 EMBRYONIC PHASE

Green fluorescence tagged stem cells in the

EMBRYONIC PHASE

A diverticulum appears on the area developing lung

of the foregut, that later develops into
the trecheobronchial tree

Like in the kidney, it appears also here that an

epithelio-mesenchymal interaction is important for
the normal development of the lungs.
EMBRYONIC PHASE EMBRYONIC PHASE

A. – B. RESPIRATORY DIVERTICULUM : ---- Larynx and Trachea

(endodermal)

C. – D.- E. LUNG BUDS : ---- primary bronchus, secondary br., tertiary br.,
bronchioles, terminal bronchioles, respiratory
bronchioles, alveolar ducts, alveoli. (20-24 orders).
 MATURATION OF THE LUNGS:
- Pseudo glandular Period (5-17 weeks) ---
- Canalicular Period ( 16-25 weeks) ---
- Terminal Sac Period (24- birth) ---
- Alveolar Period (Late fetal period) ---
EMBRYONIC PHASE
resemble an exocrine gland
Respiration not possible
respiratory bronchioles and alveolar
ducts present.
Respiration possible.
thin alveolar epithelium
Type I cells (pneumocytes);
Type II cells (secrete surfactant).
Fetus can survive.
alveolocapillary membrane
(respiratory membrane)
Gas exchange possible.
MATURATION OF LUNG

Terminal Sac Period (24- birth) --- thin alveolar epithelium

Fetus can survive. Type I cells (pneumocytes);
Type II cells (secrete surfactant).
 EMBRYONIC – PSEUDOGLANDULAR
PHASE
EMBRYONIC PHASE

POSSIBLE CONGENITAL
ANOMALIES

CANALICULAR PHASE
CLASSIFICATION IN THE ADULT LUNG
 THE BRONCHIAL TREE
(BRONCHO-PULMONARY SEGMENTS)
CLASSIFICATION IN THE ADULT LUNG

The bronchopulmonary segment is the

anatomical, functional, and surgical
unit/subdivision of the lung and refers to
the portion of the lung supplied by each
segmental/tertiary bronchus and
segmental/tertiary artery.
 LUNG LOBULE
CLASSIFICATION IN THE ADULT LUNG

Each lung lobule

is supplied by a
single terminal
bronchiole

Each terminal
bronchiole formed
by the dividing of a
segmental
bronchus supplies
a unit of the lung
called a lung
lobule. The lung
lobule is the basic
functional unit of
the lung.
CLASSIFICATION IN THE ADULT LUNG

1 Ciliated epithelium
2 Goblet cell
3 Gland
4 Cartilage
5 Smooth muscle cell
6 Clara cell
7 Capillary
Diagrams for comparing the constructions of
8 Basal membrane
the walls in the respiratory tract.
9 Surfactant
According to their function the respiratory 10 Type I pneumocyte
tract passages are divided into conducting and 11 Alveolar septum
respiratory zones: 12 Type II pneumocyte
THE ALVEOLUS

Adjacent alveoli share a common

wall called the interalveolar
septum which contains the
capillary system of the
pulmonary circulation. Adjacent
alveoli also communicate by
small apertures (i.e., <10 μm in
diameter) within the
interalveolar septa called
alveolar pores.

Interalveolar Septum: refers to the

tissue which separates adjacent
alveoli. It contains the extensive
alveolar capillary plexus and thus
represent the site where the
diffusion of gases takes place
between alveolar air and capillary
blood.
THE ALVEOLUS
Alveolar Cell Types:
a. Type I Pneumocytes: are very flat squamous cells
that are so thin that their cytoplasm cannot be seen in
the light microscope. Apart from the perinuclear region,
these cells are less than 0.2 μm thick which facilitates
the diffusion of gases across their cytoplasm.
b. Type II Pneumocytes: are connected to the type I
cells by tight junctions and are distinguished by their
discernible cytoplasm and more rounded appearance.
Have a round nucleus and their cytoplasm tends to bulge
somewhat into the lumen. These are secretory cells,
whose major product is pulmonary surfactant.
c. Alveolar Macrophages: are large phagocytic cells
that bulge into the lumen. Often they appear to be free
in the lumen but are actually loosely attached to the
epithelium. Like other macrophages, these cells
phagocytose material, in this case dust and debris that
gain access to the alveoli.

Alveolar-Capillary Barrier: Air within the alveolus is

separated from capillary blood by the following
structures: 1) cytoplasm of the type I pneumocyte; 2)
the fused basement membranes of the alveolar
epithelium and endothelium; 3) cytoplasm of the
endothelial cell. Altogether, the distance that gas
molecules must diffuse is between 0.2 and 2.0 μm.
Type I Pneumocytes: are very
flat squamous cells that are so
thin that their cytoplasm cannot be
seen in the light microscope.
Apart from the perinuclear region,
these cells are less than 0.2 μm
thick which facilitates the diffusion
of gases across their cytoplasm.
Alveolar Macrophages: are
large phagocytic cells that
bulge into the lumen. Often
they appear to be free in the
lumen but are actually loosely
attached to the epithelium. Like
other macrophages, these cells
phagocytose material, in this
case dust and debris that gain
access to the alveoli.
Type II Pneumocytes: are connected to
the type I cells by tight junctions and are
distinguished by their discernible cytoplasm
and more rounded appearance. Have a
round nucleus and their cytoplasm tends to
bulge somewhat into the lumen. These are
secretory cells, whose major product is
pulmonary surfactant.
MOVEMENTS OF THE THORAX
The ribs and
diaphragm
move in
such a way
that three
dimensions
of the
thoracic
cavity are
increased
 MECHANISM OF RESPIRATION
Inspiration (normally active):

Thoracic (intercostal nerves)

- Upper 6 prs ribs – increase a-p diameter – pump handle movements
- Lower 7 to 10 prs ribs – increase lateral diameter – bucket handle movements

Abdominal (phrenic nerves)

- Diaphragm – increases inferior-superior dimension

Expiration (normally passive):

- Due to recoil of lungs and tissues

Note: In forced respiration accessory muscles come into action!!

 Respiratory centres & Reflex centres

The Pneumatic and

Apneustic centres
adjust the output of Higher centres can
the rhythmicity influence respiration
centre, thereby through pneumatic
modifying the pace centre. Pyramidal
of respiration. provides conscious
control to resp. muscles,
but usually by
Pneumatic extrapyramidal
centre pathways (reticular
formation).
Apneustic
centre

The Rhythmicity
centres set the basic Inspiratory ctr
pace and depth of
respiration. Exspiratory ctr
 THANK YOU

FOR YOUR PATIENCE

HT SEPTEMBER 2012
The lumen of the tubules becomes wider and a part of the epithelial cells
get to be flatter. From the cubic type II pneumocytes develop the
flattened type I pneumocytes.

A sufficient differentiation of the type II pneumocytes into the type I

pneumocytes and the proliferation of the capillaries into the
mesenchyma marks an important step towards the fetus being able
to survive outside the uterus after roughly the 24th week of
pregnancy.

From the last trimester whole clusters of sacs form on the terminal
bronchioli, which represent the last subdivision of the passages that
supply air. In the saccular phase the last generation of air spaces in the
respiratory part of the bronchial tree is born.

At the end of each respiratory tract passage smooth-walled sacculi

form, coated with type I and type II pneumocytes.
 Probably in the last few weeks of the pregnancy, new sacculi and, from
them, the first alveoli form.

Thus, at birth, ca. 1/3 of the roughly 300 million alveoli should be fully
developed. The alveoli, though, are only present in their beginning forms.

In the adult lung one distinguishes between conducting and respiratory

zones.
In the conducting zone, all branches of the bronchial tree, the walls of
which contain cartilage tissue and seromucous glands, are bronchi. As soon
as cartilage and glands are no longer present, bronchioli are involved.

The transition from in utero to ex utero life forces the infant to adapt to new
environmental conditions and stimuli, and depending on how premature
an infant is, that infant may not be able to adequately compensate for the
changes.
As a result extremely premature infants are vulnerable to lung injury and
abnormal lung remodeling, which manifests itself through chronic lung
dysfunction. In continuing to understanding the molecular mechanisms that
control lung development and growth, researchers and clinicians can develop
or re-evaluate treatment strategies, for premature infant so to maximize lung
maturation, while minimizing lung injury.
For the branching out of ever new lung buds an interaction between the
respiratory endodermal epithelium and the surrounding pulmonary mesenchyma
is primarily responsible. Mainly the epidermal growth factor (EGF) and the
extracellular form of the transforming growth factors (TGF-b) appear to be
important for lung development.
In addition, one finds specific extracellular matrix components like collagen of
types I and III, as well as proteoglycan and the fibronectin and syndecan
glycoproteins. These molecules are found around the passages and in the forks of
the bronchial tree. They are responsible for the stabilization of the already formed
structures - these are not present in the regions of the newly formed branches.
Epimorphine, a further protein, appears to promote the formation of epithelial
passages. If epimorphine is blocked by antibodies, the epithelium that lies above it
can not form itself into tubes and remains unorganized. (5)