Download Development anatomy of the respiratory organ

Development anatomy of the
respiratory organ
3
Organ respiratoria
• Upper respiratory
organs
• Nose
• Nasal cavity
• nasopharynx
• Lower respiratory
organs
• Larynx
• Trachea
• Bronchi
• lung
Embrio mg ke-2
• Mg pertama:
Tahapan
embrioblast:
zygot –hasil
fertilisasi –
blastomer –
morula (16 sel)3 hariblastokista –
implantasi 6
hari
Lapisan embriologi:
• 2 lapisan (bilaminer)
cakram embrional:
minggu ke 2- epiblast
dan hipoblast
• 3 lapisan embriologi
(gastrulasi): mg ke 3
embrional (hari ke 17)
• Ectoderm (epiblast)
• Mesoderm (epiblast)
• Endoderm
(hypoblast)
Endoderm
Usus enteron
primitif
Usus depan
Pre entero
anterior
Mulut, esophagus,
gaster, duodenum
(partim)
Saluran pernafasan
Trachea, pulmo
Thymus, thyroid
Hati, pancreas
Usus tengah
Mesentero
Usus belakang
Met enteron
caudal
Duodenum, jejenum
Ileum, colon ascen
Colon transv (part)
Colon trans (part)
Colon desc, colon
Sigmoid, rectum
Vesica urinaria,
urethra
Embriologi: bagian thorax
• Minggu ke 3 (hari 15 – 21)
embrional: embrio
• bagian cranial - caput –
otak (hari 20) somite
batang trunkus – somite,
heart tuba fused
bagian caudal
sisi ventral
sisi dorsal
• Minggu ke 4: trunkus – limb
bud- kuncup lengan-arm
bud (hari ke 26), leg bud
(hari 28), heart bulg
somite
Development of face:nose
• Nasal placodes and medial
and lateral nasal processes
• Nasal cofactor placode:two
ectodermal elevation on
each side of median plane
of frontonasal process –and
surface depression, and the
edges become nasal
process, the lateral more
prominent, forms alae of
nose
• Medial process merge each
other, as result growing of
maxillar eminence (maxillar
process), become middle
part of upper lip, upper jaw,
primary palate
• Remains of maxillar process
become cheek
• Mandibular process: lower
lip and lower jaw
• Formation eyes: from lens
placode;Formation external
ear, from ectodermal cleft
from series mesodermal
thickening (pinna)
Development of nasal
cavity
• Formation of nasal septum,
the nasal sacs, separated
each other by the with
• Formation of nasal pit, after
intervening part of
primitive palate formed by
frontonasal process
fusion lateral and medial
• Secondary palate, separates
nasal processes, created
nasal cavities from mouth
partition between nasal pits
cavity
and stomatodeum
• Formation structures of
• Formation of nasal
lateral wall:lateral nasal
sacs,nasal pits deepen and
process, nasal conchae,
enlarge dorsally, caudally
olfactory epithelium
form nasal sacs
(ectodermal thickening)
• Posterior part of nasal sacs,
• Paranasal sinus:xaxillary and
separated by buconasal
sphenoid formed end of
membrane, and soon
fetal life, other formed after
disappears, forming
birth
posterior nares
• pharynx:cephalic (prelaryngeal) of foregut
(from buccopharyngeal
membrane to
tracheobroncheal
diverticulum)
• Definitive
pharynx:primitive
pharynx after formed
branchial apparatus
(palate & mouth)
• Nasopharynx: communicate
ventrally, forms cranial part
of stomatodeum after
formation palate
• Nasopharynx: from
stomatodeum after
ruptured buccopharyneal
membrane
• Laryngopharynx:
tracheobronchial
diverticulum
Anomaly of nasal cavity
• Atresia of nasal cavity
• Anomaly of nasal septum, deflected of nasal
septum and absence of septum
• Cleft palate (abnormal communication mouth
and nasal cavity)
Primordia lower respiratory organs
• Respiratory
diverticulum (lung bud):
endodermal structures
from foregut, forms
epithelial lining
• Splanchnic
mesoderm;surrounding
lungbud: forms
cartilagenous part,
muscular, connective
tissue component
• Fourth and six
pharyngeal arches,
forms cartilage (thyroid,
cricoid, arytenoid,
corniculata, cuneiform)
and muscle of larynx
(intrinsic muscle),
cricothyroid, contrictor
of pharynx muscles :
innervasi n vagus
(superior laryngeal &
recurrent laryneal)
• LARYNX
VC5-VC7
Skeleton laryngis:
cartilago laryngis
Epiglottica (elastis)
thyroidea (hyalin)
cricoidea
arytenoidea
corciculata
cuneiforme
Articulatio
cricothyroidea
cricoarytenoidea
Embriologi rongga tubuh
Rongga rongga tubuh
• Pembentukan selom intraembrional
mg 3: sebelumnya – rongga amnion, selom
ekstraembrional, kantong kuning telur
• Akhir mg 3; mesoderm lateral – somatik & splanknik -- selom intraembrional (dada sampai panggul)
• Lapisan somatik – lapisan parietal membran serosa –
rongga peritoneum, pleura dan kantong
jantung;Lapisan splanknik – lapisan visceral m. serosa
nya – di dorsal sbg mesenterium dorsale, dan di
ventral sbg mesenterium ventrale (di usus depan) krn
ada septum transversum
Diaphragma dan rongga dada
• Septum transversum – sekat mesoderm : rongga dada –
tangkai kantong kuning telur
• Tidak memisahkan sempurna rongga dada & rongga perut
• Lubang: saluran perikardioperitoneal di kiri kanan usus depan
• Ada tunas pulmo, tumbuh cepat di dalam saluran
perikardioperitoneal, lipatan pleuroperikardial – rigi
menonjol – ruang dada primitif, pulmo meluas, rongga
mesoderma dinding tubuh – dibelah 2 komponen:dinding
dada definitif dan membrana pleuroperikardial
• Jantung turun, sinus venosus, membrana tertarik keluar –
rongga dada; rongga perikardium tetap & dua rongga pleura
tetap
Rongga dada & perut serta diaphragma
• Mg ke 7: rongga dada & perut tertutup oleh
selaput pleuroperitoneal (: lipatan
pleuroperitoneal), septum transversom,
mesenterium esophagus--- mioblas dinding
tubuh membentuk bagian otot diaphragma
• Klinis : hernia diaphragmatica
Embriologi diaphragma
• Septum transversum
(bag tendinosa)
• Mioblast dinding tubuh
lateral & ventral (bag.
Muscular)
• Selaput
pleuroperitoneal (sekat
yang ditempati mioblas)
• Mesenterium
esophagus (crura)
Perkembangan bagian badan
Derivat
3 lapisan embrional
di thorax
endoderm
Esophagus (fore gut),
Pulmo (fore gut)
Thymus –
saccus pharyngealis
mesoderm
Jantung,
pembuluh darah
Mesoderma somatik
ectooderm
Mesoderma splanknik
Somite: skelotome
(tulang); otot
(dermomiotome)
Medulla spinalis:
basalis (ventral) &
alaris (dorsalis
Sel crista neuralis
Embriologi trachea & pulmo
• Embrio 4 mg: tunas pulmo (diverticulum
respiratorium) – tonjolan keluar dari dinding ventral
usus depan
• Epitel – larynx, trachea, bronchus, epitel paru dari
endoderm
• Tulang rawan, otot polos – dari mesoderma
splanknik sekeliling usus depan
• Rigi esophagotrachealis – septum – trpisah:
esophagus & trachea dan tunas pulmo
Phases of lung development
• Embryonic phase
• Pseudoglandular phase
• Canalicular phase
• Saccular phase
• Alveolar phase
• Classification in the adult lung
• 1Foregut
2Anlage of the thyroid
3Anlage of the lungs
4Stomach
• 5Anlage of the dorsal
pancreas
6Midgut
7Hindgu
• The embryonic phase of lung
development begins with
embryonic phase
the formation of a groove in
the ventral lower pharynx,
the sulcus laryngotrachealis • Thus the asymmetry of the
(stage 10, ca. 28 days, 10 ).
main bronchi, as they present
in adults, is already
• After a couple of days - from
established.
the lower part - a bud forms,
• The subsequent divisions of
the true lung primordium
the endodermal branches also
(stage 12, ca. 30 days, 12 ).
take place unequally in that on
• In the further subdivision
the right three further buds
into the two main bronchi
form and, on the left, only
(stage 14, ca. 33 days, 14 )
two, corresponding to the
the smaller bud on the left is
later pulmonary lobes.
directed more laterally than • In the next division step, which
the somewhat larger one on
occurs at the end of the
embryonic period, the
the right that - parallel to
segments of the individual
the esophagus - is directed
pulmonary lobes arise.
more caudally.
• 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.
• 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.
• From the aortic sac a vessel
plexus arises around the lung
anlagen that with the lung buds
extends caudally.
• 1First aortic arch
(atrophying)
2Second aortic arch
3Third aortic arch (internal
carotid artery forms from the
ventral part)
4Fourth aortic arch (on the right:
part of the subclavian artery, left:
arcus aortae)
• 5Dorsal aorta
6Lung buds
7Aortic sac
8Pulmonary plexus
• At this stage the lungs resemble
the development of a tubuloacinous 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
ducts have already been formed.
The primordial system of
passages, the air-conducting
bronchial tree, is initially coated
by cubic epithelium
Pseudoglandular phase
• 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 bronchopulmonary epithelium begins to
produce amniotic fluid, which is
also found in the lungs up to the
time of birth.
the pseudoglandular phase
• In the pseudoglandular phase the
lungs resemble a gland. At the
end of this phase the precursors
of the pneumocytes can be
discerned in the respiratory
sections as cubic epithelium.
• 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 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, airconducting 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.
• f 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 the canaliculi branch
out of the terminal bronchioli.
• The canaliculi compose the
proper respiratory 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 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.
•
The type I pneumocytes
differentiate out of the
type II pneumocytes.
The capillaries approach
the walls of the acini
canalicular phase
•
•
•
•
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)
The surfactant (abbreviation for
surface 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.
•
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.
•
In this stage developmental damage
already affects the gas-exchange
components and result in structural
alterations of the later pulmonary
parenchyma.
• 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 smoothwalled 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.
• The capillaries multiply
around the acini. They
push close to the
surface and form a
common basal
membrane with that of
the epithelium
• 1. Type I pneumocyte
2Type II pneumocyte
3Capillaries
• he blood-air barrier in the lungs is
reduced to three, thin layers: type
I pneumocyte, fusioned basal
membrane, and endothelium of
the capillary.
• 1Type I pneumocyte
2Saccular space
3Type II pneumocyte
4Basal membrane of the air
passage
5Basal membrane of the
capillaries
6Endothelium of the capillaries
the saccular phase,
• 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.
• 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 only present
in their beginning forms.
alveolar phase
• Between them lies the
parenchyma, composed
of a double layer of
capillaries, that forms the
primary septa between
the alveolar sacculi.
• In the alveolar phase the
alveoli form from the
terminal endings of the
alveolar sacculi and with
time increase their
diameter.
• 1Alveolar duct
2Primary septum
3Alveolar sac
4Type I pneumocyte
5Type II pneumocyte
6Capillaries
• 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 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 interstitial septa
between two capillary nets.
In the first 6 months, their
number increases massively.
This "alveolarization" and
therewith the formation of
secondary septa should - to a
limited extent still - continue
up to the first year and a half
of life.
• 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.
• 1Alveolar duct
2Secondary septum
3Alveoli
4Type I pneumocyte
5Type II pneumocyte
6Capillaries
• 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.
• Diagrams for comparing the
constructions of the walls in the
respiratory tract
• 1Ciliated epithelium
2Goblet cell
3Gland
4Cartilage
5Smooth muscle cell
6Clara cell
7Capillary
8Basal membrane
9Surfactant
10Type I pneumocyte
11Alveolar septum
12Type II pneumocyte
•
•
•
•
•
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.
• Histological image of
respiratory
epithelium.Respiratory
zone = 7 generations
• Out of the terminal
bronchioli several
generation of
• Respiratory bronchioli (=
3 generations) proceed.
From them follow several
generations of
• Alveolar ducts (= 3
generations) that in
• Alveolar sacculi (last
generation = 23rd
generation) end
• 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
anomaly
• Laryngeal atresia
• Fistula tracheoesophageal
• Tracheal stenosis,
atresia
• Agenesis trachea
• Agenesis of lung
• Hyaline membrane
disease/respiratory
distress syndrome
• Tracheoesophageal
fistula
A fistula is a tube. The
esophagus is a tube
that goes to the
stomach and the
trachea is a tube that
goes to the lungs.
• Normally these two
tubes do not connect
but when a baby has a
tracheoesophageal
fistula, there is a tube
connecting the two.
This can cause problems
with feeding and even
breathing in newborns
and needs to be
corrected.
• Oesophageal Atresia
and/or Tracheoesophageal
Fistula
• Embryology Smith's theory:
The trachea and esophagus
initially begin as a single
tube. The lateral esophageal
grooves are formed as the
dorsal esophagus is
separated from the ventral
trachea. Should the
septation process continue
distally, esophageal atresia
would result. Grunewald's
theory: Elongation of the
trachea is rapid in a caudal
direction.
• When there is a fistula
producing fixation of
esophagus to trachea, the
dorsal wall of the esophagus is
drawn forward and downward
to be incorporated into the
trachea. Atresia of the
esophagus results because of
the fistula. Bronchogenic
theory: The esophagus does
not develop at all distally.
Rather, a third "bronchus"
develops in the primordial
lung bud and grows inferiorly
to attach to the stomach.
• The esophagus and
trachea derive from the
primitive foregut.
During the fourth and
fifth weeks of
embryologic
development, the
trachea forms as a
ventral diverticulum
from the primitive
pharynx (caudal part of
the foregut),5 as
illustrated in Figure 3. A
tracheoesophageal
septum develops at the
site where the
longitudinal
tracheoesophageal
folds fuse together..
• This septum divides the
foregut into a ventral
portion, the laryngotracheal
tube and a dorsal portion
(the esophagus).
Esophageal atresia results if
the tracheoesophageal
septum is deviated
posteriorly. This deviation
causes incomplete
separation of the esophagus
from the laryngotracheal
tube and results in a
concurrent
tracheoesophageal fistula
•
Successive stages in the development of the tracheoesophageal septum during
embryologic development. (A) The laryngotracheal diverticulum forms as a ventral
outpouching from the caudal part of the primitive pharynx. (B) Longitudinal
tracheoesophageal folds begin to fuse toward the midline to eventually form the
tracheoesophageal septum. (C) The tracheoesophageal septum has completely
formed. (D) If the tracheoesophageal septum deviates posteriorly, esophageal
atresia with a tracheoesophageal fistula develops.
• Relative frequencies of occurrence of the various
types of esophageal atresia (EA) with and without
tracheoesophageal fistula (TEF).
• Esophageal atresia is characterized by incomplete formation
of the esophagus. It is often associated with a fistula between
the trachea and the esophagus. Many anatomic variations of
esophageal atresia with or without tracheoesophageal fistula
have been described7,8 (Figure 4). Table 11,3,9-12 provides a
summary of the incidence of these variations at multiple
worldwide surgical centers. The most common variant of this
anomaly consists of a blind esophageal pouch with a fistula
between the trachea and the distal esophagus, which is
estimated to occur 84 percent of the time. The fistula often
enters the trachea close to the
Figure 10 Main types of tracheoesophageal fistulae
GI Motility online (May 2006) | doi:10.1038/gimo6
• he figure shows both tracheoesophageal
fistula (A-E) and tracheal abnormalities ( F-J).
Note that A-E do not correspond with the
classification of the type of tracheoesophageal
fistula. A shows type C, B type B, C type D, D
type E, and E type A tracheoesophageal
fistula, respectively. (Source: Netter medical
illustration with permission from Elsevier. All
rights reserved.)
• The main varieties of tracheoesophageal fistula. Possible directions of the
flow of the contents are indicated by arrows. Esophageal atresia, as
illustrated in A, is associated with tracheoesophageal fistula in more than
85% of cases. B, Fistula between the trachea and esophagus. In C, air
cannot enter the distal esophagus and stomach. Air can enter the distal
esophagus and stomach in D, and the esophageal and gastric contents
may enter the trachea and lungs.
• Classification (Gross's Anatomical Classification)
• Type A: Esophageal atresia without tracheoesophageal fistula.
• Type B: Esophageal atresia with proximal tracheoesophageal
fistula.
• Type C: Esophageal atresia with distal tracheoesophageal
fistula (most common type) (85%).
• Type D: Esophageal atresia with proximal and distal fistula.
• Type E: Tracheoesophageal fistula without atresia. (Not
shown)