alamat buku psh

8/2/2019 alamat buku psh

1/13

Learning aims

www.embryology.ch/indexen.htmlAt the end of this module you should be able to:

know the various prenatal stages of lung development.

be able to list and localize the various cells that are typical for

lung tissue.

know the components of the blood-air barrier.

be able to describe the development of the various somatic

cavities.

know where the pericardio-peritoneal duct lies.

know the difference between the vasa publica and privata in thelungs.

be able to explain the occurrence of fistulas between the

esophagus and trachea based on your knowledge of the

development of the two structures.

know the various mechanisms in charge of the switch of the

circulation systems at birth.

What you should already know

Embryogenesis

Cardiovascular system

Introduction

The respiratory system starts to develop with an inconspicuous laryngo-

tracheal groove (stage 10, ca. 28 days, 10 ) that forms in the ventral

midline at the lower end of the pharynx. The caudal part of this groove

develops into the lung anlage in that it divides into right and left lung

buds (stage 12, ca. 30 days, 12 ). The upper part of this groove

remains undivided and becomes the trachea.

The two lung buds extend and form the main bronchus (stage 14, ca. 33

days, 14 ). These subdivide further and form 2 (on the left side) and 3

(on the right) lobular buds and thus the lobular bronchi. The whole lung

development takes place in five main phases that partially overlap (4);

followed by a maturation stage:
http://openscroll%28%2710%27%29/http://openscroll%28%2710%27%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#04http://openscroll%28%2714%27%29/http://openscroll%28%2714%27%29/http://openscroll%28%2712%27%29/http://openscroll%28%2712%27%29/http://openscroll%28%2710%27%29/http://openscroll%28%2710%27%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#04


2/13

Embryonic phase (3rd - 8th week)

Pseudoglandular phase (5th - 17th week) Canalicular phase (16th - 26th week)

Saccular phase (24th week up to birth)

Alveolar phase (36th week up to the 18th month post partum)

Stage of the microvascular maturation (from birth to 2 - 3 years)

Fig. 1 - Overview of the intrauterine phases of lung development

Adult lungs have an inner surface area of140 m2. This extent can only be

achieved through an enormous increase in the inner complexity of the

pulmonary parenchyma. This is described in the following chapters.

Delving deeper

Why does a laryngo-tracheal groove form in the ventral part of the foregut?

What are the mechanisms underlying the dichotomous division of the bronchi?

Why does further branching normally occur distally in the bronchial tree and not in the

trachea?

Embryonic phase QuizQuiz 02

The embryonic phase of lung development begins with the formation of a

groove in the ventral lower pharynx, the sulcus laryngotrachealis (stage

10, ca. 28 days, 10 ). After a couple of days - from the lower part - a

bud forms, the true lung primordium (stage 12, ca. 30 days, 12 ). In

Quiz

Quiz 11
http://void%280%29/http://openscroll%28%2710%27%29/http://openscroll%28%2712%27%29/http://openscroll%28%2710%27%29/http://void%280%29/http://openscroll%28%2710%27%29/http://openscroll%28%2710%27%29/http://openscroll%28%2710%27%29/http://openscroll%28%2710%27%29/http://void%280%29/http://openscroll%28%2712%27%29/http://void%280%29/


3/13

the further subdivision into the two main bronchi (stage 14, ca. 33 days,

14 ) the smaller bud on the left is directed more laterally than the

somewhat larger one on the right that - parallel to the esophagus - isdirected more caudally. Thus the asymmetry of the main bronchi, as they

present in adults, is already established. The subsequent divisions of the

endodermal branches also take place unequally in that on the right threefurther buds form and, on the left, only two, corresponding to the later

pulmonary lobes. In the next division step, which occurs at the end of the

embryonic period, the segments of the individual pulmonary lobes arise.

Quiz

Quiz 03

More info

It appears that the branching and growth of the lung anlage is under the

direction of the mesenchyma on which it lies. Like in the kidney, it

appears also here that an epithelio-mesenchymal interaction isimportant for the normal development of the lungs. This is shown by

recombination experiments in which the tracheal epithelium begins to

fork when it is grown on a layer of bronchial mesenchyma. (6) .

At the end of the embryonic period the first segments appear in the five

(three right and two left) lobes of the lungs. With their distended ends the

lungs resemble an exocrine gland.

At this time the pulmonary vessels have formed themselves.

Development of the lungs up tothe end of the embryonic period

1

2

3

4

5

6

7

Right main bronchus

Upper right pulmonary

lobe

Middle pulmonary lobe

Lower right pulmonary

lobe

Left main bronchus

Upper left pulmonary

lobe

Lower left pulmonarylobe
http://void%280%29/http://openscroll%28%2714%27%29/http://void%280%29/http://www.embryology.ch/anglais/turinary/urinhaute01.htmlhttp://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#06http://void%280%29/http://openscroll%28%2714%27%29/http://openscroll%28%2714%27%29/http://void%280%29/http://www.embryology.ch/anglais/turinary/urinhaute01.htmlhttp://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#06http://void%280%29/


4/13

The pulmonary circulation system (smaller circulation system) is formed

out of the 6th pharyngeal arch artery. These develop somewhat

differently than the other 4 aortic arches in that first a vessel plexus forms

around the lung anlage, originating from the aortic sac. The true 6th

aortic arch is only then formed after vessels - also from the dorsal aorta -

grow into this plexus and thus a connection between the truncus

pulmonalis and dorsal aorta has arisen.

Fig. 3 - Development of thepulmonary vessels in stage 13

Fig. 4 - Development of thepulmonary vessels in stage 15

Legend

1

2

3

4

First aortic arch

(atrophying)

Second aortic arch

Third aortic arch

(internal carotidartery forms from the

ventral part)

Fourth aortic arch

(on the right: part

of the subclavian

artery, left: arcus

aortae)

5

6

7

8

Dorsal aorta

Lung buds

Aortic sac

Pulmonary plexus

Fig. 3

From the

aortic sac a

vessel

plexus

arises

around the

lung anlagen

that with

the lungbuds extends

caudally.

Fig. 4

Also from

the dorsal

aorta a

vessel

plexus forms

that soon

communicates

with the

ventral one

and thus

creates a

connection

between the

ventral

aortic sac

and the

dorsal


5/13

aorta. On

the left the

arterialduct arises

from it.

Pseudoglandular phase QuizQuiz 04

At this stage the lungs resemble the development of a tubulo-acinous

gland. According to the classical view, the entire air-conducting

bronchial tree up to the terminal bronchioli are set down in this phase

(16 generations). Recent morphometric studies (3) have shown that with

the end of the pseudoglandular phase 20 generations are partially present

in the lungs, which means that at this point in time the respiratory ductshave already been formed.

The primordial system of passages, the air-conducting bronchial tree, is

initially coated by cubic epithelium. These are the precursor cells of the

ciliated epithelium and of the secretory cells. In humans, the first

ciliated epithelial cells can be found in the 13th week of pregnancy (7).

In the respiratory part the first

typically lung-specific cells,

connected to the terminal

bronchioli, appear:

the type II pneumocytes(alveolar cells) (3).

The developing broncho-

pulmonary epithelium begins to

produce amniotic fluid, which

is also found in the lungs up to

the time of birth.

Fig. 5 - Lung tissue in the

pseudoglandular phase

Legend

1

23

Lung mesenchyma

Type II pneumocytesCapillaries

Fig. 5

In the

pseudoglandularphase the lungs

resemble a

gland. At the

end of this

phase the

precursors of

the pneumocytes

can be

discerned in

the respiratory

sections ascubic

epithelium.

More info

Relatively early in the development of the lungs, endocrine-active cells

(Kultschitsky cells) appear that produce bombesin and serotonin. In

contrast to the precursors of the pneumocytes, which originate from the

endoderm, they stem from the neural crest (neuroectoderm). Via
http://void%280%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#03http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#07http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#03http://www.embryology.ch/images/vnervous/v03vesicule/v3g_lamalaire.gifhttp://void%280%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#03http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#07http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#03


6/13

paracrine mechanisms bombesin probably plays a decisive role for

lung development in that mainly the type II pneumocytes proliferate. (1)

The differentiation of the lungs takes place in a centrifugal direction. In

the central, air-conducting portions of the lungs the epithelium begins

to differentiate into cilia-carrying cells and goblet cells. After the 10th

week cartilage and smooth muscle cells as well as bronchial glands can

be found in the wall of the bronchi. The peripheral sections partially

retain - until far beyond the pseudoglandular phase - cubic epithelium that

is still little differentiated. This is important for a further proliferation of

the bronchial tree into the surrounding mesenchymal tissue.

More infoIf one begins, roughly estimated, with a number of 15'000 terminal

bronchioli (8) per lung in adults and thereby ca. 15,000 acini and with a

theoretical assumption of a dichotomous division of the pulmonary

branches, one has the result that this stage is attained after little fewer

than 2 14 generations. In the late pseudoglandular stage one finds,

however, far more than 15'000 end pieces. Thus the lung end pieces at

this stage already represent the respiratory portions of the lungs.

Canalicular phase

In the classical description of lung development, in this phase thecanaliculi branch out of the terminal bronchioli. The canaliculi

compose the properrespiratory part of the lungs, the pulmonary

parenchyma. All of the air spaces that derive from a terminal

bronchiolus form an acinus. Each one comprises respiratory

bronchioli and the alveolar ducts and later the alveolar sacculi. The

chief characteristic of this canalicular phase is the alteration of the

epithelium and the surrounding mesenchyma. Along the acinus, which

develops from the terminal bronchiolus, an invasion of capillaries into

the mesenchyma occurs. The capillaries surround the acini and thus form

the foundation for the later exchange of gases. The lumen of the tubules

becomes wider and a part of the epithelial cells get to be flatter. From thecubic type II pneumocytes develop the flattened type I pneumocytes.

More infoHistological

image of the

canalicular

phase of

lung

development

A sufficient differentiation of the

type II pneumocytes into the type I

Fig. 6 - Lung tissue in the

canalicular phase

Legend
http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#01http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#08http://void%280%29/http://void%280%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#01http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#08http://void%280%29/http://void%280%29/


7/13

pneumocytes and the proliferation

of the capillaries into the

mesenchyma marks an importantstep towards the fetus being able

to survive outside the uterus after

roughly the 24th week of

pregnancy.

1

2

3

Type I pneumocytes

Type II pneumocytes

Capillaries

Fig. 6

The type I

pneumocytesdifferentiate

out of the

type II

pneumocytes.

The

capillaries

approach the

walls of the

acini.

More info

The first breathing movement can be registered already at the end of the

embryonic period. They are controlled by a breathing center in the brain

stem. Nevertheless, these breathing movements are paradoxical in that

when the diaphragm contracts, the thorax moves inwardly and vice

versa. (2)

At the end of this canalicular phase which is the beginning of the

saccular phase (ca. 25 weeks) - a large part of the amniotic fluid is

produced by the lung epithelium. From this time on, the maturity of the

lungs can be measured clinically based on the activity of the type II

pneumocytes, which begin to produce the surfactant. The ratio of

lecithin to sphingomyelin in the amniotic fluid, which increases with

fetal age is determined. I

In this stage developmental damage already affects the gas-exchange

components and result in structural alterations of the later pulmonary

parenchyma.

More info

The surfactant (abbreviation forsurface active agent) consists of

glycerophospholipids, specific proteins, neutral fats and cholesterol.

It covers the alveolar surface and reduces the surface tension so that,

following birth, the alveoli do not collapse during the expiration.

Saccular phase QuizQuiz 05
http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#02http://void%280%29/http://www.embryology.ch/images/vnervous/v03vesicule/v3g_lamalaire.gifhttp://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#02http://void%280%29/


8/13

From the last trimester whole clusters ofsacs 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 therespiratory 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. The septa (primary septa) between the sacculi

are still thick and contain two networks of capillaries that come from the

neighboring sacculi. The interstitial space is rich with cells and the

proportion of collagen and elastic fibers is still small. This matrix,

though, plays an important role for the growth and differentiation of the

epithelium that lies above it (9).

At the end of this phase the interstitial fibroblasts begin with the

production of extracellular material in the interductal and intersaccular

space.

Fig. 7 - Histological scheme of

the saccular phase

Fig. 8 - Blood-air barrier in the

lung

Legend

1

2

3

Type I pneumocyte

Type II pneumocyte

Capillaries

1

2

3

4

5

6

Type I pneumocyte

Saccular space

Type II pneumocyte

Basal membrane of the

air passage

Basal membrane of the

capillaries

Endothelium of the

capillaries

Fig. 7

The

capillaries

multiply

around the

acini. They

push close

to the

surface and

form a

common basal

membrane

with that of

the

epithelium.

Fig. 8

The blood-

air barrier

in the lungs

is reduced

to three,

thin layers:

type I

pneumocyte,

fusioned

basal

membrane,

and
http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#09http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#09


9/13

endothelium

of the

capillary.

At birth, i.e., at the end of the saccular phase, all generations of the conducting and

respiratory branches have been generated. The sacculi are thin, smooth-walled sacks and

correspond to the later alveolar sacculi.

Alveolar phase

Depending on the author, the alveolar phase begins at varying times.

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 onlypresent in their beginning forms. Between them lies the parenchyma,

composed of a double layer of capillaries, that forms the primary septa

between the alveolar sacculi.

Fig. 9 - Alveolar phase before birth Legend

12

3

4

5

6

Alveolar duct

Primary septum

Alveolar sac

Type I pneumocyte

Type II pneumocyte

Capillaries

Fig. 9

In the

alveolar

phase the

alveoli form

from theterminal

endings of

the alveolar

sacculi and

with time

increase

their

diameter.

Already before birth these alveolar sacculi get to be increasingly complex

structurally. Thereby, a large number of small protrusions form along the

primary septa. Soon, these become larger and subdivide the sacculi into


10/13

smaller subunits, the alveoli, which are delimited by secondary septa.

Ultrastructural investigations show that overall where such alveoli

appear, they are surrounded by elastic fibers that form the interstitialsepta between two capillary nets.

In the first 6 months, their number increases massively. This

"alveolarization" and therewith the formation ofsecondary septa should

- to a limited extent still - continue up to the first year and a half of life.

Fig. 10 - Alveolar phase following birth Legend

1

2

3

4

5

6

Alveolar duct

Secondary septum

Alveoli

Type I pneumocyte

Type II pneumocyte

Capillaries

Fig. 10

In the

alveolar

phase after

birth more

and more

alveoli form

from the

terminal

endings of

the alveolar

sacculi and

with time

increase in

diameter.

They are

delimited by

secondary

septa.

Classification in the adult lung QuizQuiz 06

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.

Quiz

Quiz 13

Quiz

Quiz 07

Fig. 11 - Overview of the wall construction in the lungs Legend
http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/


11/13

1

2

3

4

5

6

7

8

910

11

12

Ciliated epithelium

Goblet cell

Gland

Cartilage

Smooth muscle cell

Clara cell

Capillary

Basal membrane

SurfactantType I pneumocyte

Alveolar septum

Type II pneumocyte

Fig. 11

Diagrams for

comparing theconstructions

of the walls

in the

respiratory

tract.

According to their function the respiratory tract passages are divided into

conducting and respiratory zones:

Conducting zone = 16 generations

Segmental bronchi are continued by several generations of Intersegmental bronchi (up to ca. 1 mm diameter). After these

follow the

Bronchioli (< 1mm diameter) that after several divisions go over

into

Terminal bronchioli (ca. 0.4 mm diameter). They subdivide

numerous times and represent the end stretch of the purely

conductive respiratory tract. The measurements come from

histological findings.

More info

Histological

image of

respiratory

epithelium.

Respiratory zone = 7 generations More info
http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/


12/13

Out of the terminal bronchioli several generation of

Respiratory bronchioli (= 3 generations) proceed. From themfollow several generations of

Alveolar ducts (= 3 generations) that in

Alveolar sacculi (last generation = 23rd generation) end

Histological

image of an

alveolarduct.

Fig. 12 - Overview of prenatal lung development

More info

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-) 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
http://void%280%29/http://void%280%29/http://void%280%29/http://void%280%29/


13/13

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)
http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#05http://www.embryology.ch/anglais/rrespiratory/bibliorespi01.html#05

Date post:	05-Apr-2018
Category:	Documents
Upload:	muhammad-luqman-hakim
View:	233 times
Download:	0 times

alamat buku psh

Documents