Histology of the

respiratory system

Birhane Alem: Ass. Professor of Anatomy

and Histo-embryology.
1
 Objectives
At the end of this course you are expected to:
Describe the anatomical and functional division of the
respiratory system.
Discuss Respiratory Epithelium and its cell composition.
Identify the main region of the Nasal cavity.

Discuss the histological features of Larynx.

Describe the histological features of Trachea.
Identify the basic distinguishing feature of the bronchial
tree.

2
 Reference
Junqueria LC & carneiro J. basic histology.
12th ed., Mcgraw- hill.
Gartner lp& hiatt jl.textbook of histology 3
nded wb saunders, philadelphia.

Michael h. Ross- wejciech-pawlina (2010).

Histology: A text and atlas with
correlated cell and molecular biology

3
Important points to be successful
in teaching learning processes
Do not allow your cell phone to ring in class.

Avoid side conversations during lecture.

Do not show up for class late or unprepared

Show respect for your fellow students, staff and

others.
Frequently review course material.
Read all of the assignments.

Practice what you learn

Encourage peer discussions and explicate

4 what
 Respiratory System

Includes the lungs and a branching system

of tubes that link the sites of gas exchange
with the external environment.
Air is moved through the lungs by a
ventilating mechanism, consisting of the:
Thoracic cage.
Intercostals muscles.
Diaphragm.
Elastic components of the lung tissue.

5
 Respiratory System

Is divided
anatomically
into:
1. Upper
respiratory
system:- nose,
pharynx, larynx
and upper
trachea
2. Lower
respiratory
system: lower
6
trachea, bronchi
 Respiratory System
Functionally divided in to:
A. Conducting portion
. Consists of the nasal
cavities, nasopharynx,
larynx, trachea, bronchi (gr.
Bronchos, windpipe),
bronchioles, and terminal
bronchioles
. Serves two main functions:
To provide a conduit
through which air moves
to and from the lungs
To condition the inspired 7
 Respiratory System
B. Respiratory portion:-
Consisting of respiratory bronchioles,
alveolar ducts, and alveoli (functional unit
of respiratory system)
Is the main site of gas exchange between air
and blood.

8
 Respiratory Epithelium
Most of the conducting portion is lined with
ciliated pseudo stratified columnar epithelium
known as respiratory epithelium.
This epithelium has at least five cell types, all
of which touch the thick basement
membrane:
Ciliated columnar cells - the most
abundant cell found on its apical surface. -
move mucus
Goblet cells - scattered in the epithelium,
filled in their apical portions with granules
of mucin glycoprotein. - produce mucous.
9
 Respiratory Epithelium - cell
types
Brush cells
Non-ciliated columnar cells with microvilli
on the free surface probably secrete a
serous fluid which keeps the mucosa moist.
Sparsely scattered and less easily found
Have afferent nerve endings on their basal
surfaces and are considered to be
chemosensory receptors.

10
 Respiratory Epithelium

Small granule cells (neuoendocrine cells (K cell)

-peptide)
Are also difficult to distinguish in routine
preparations.
Possess numerous dense core granules 100300
nm in diameter.
Like brush cells, they represent about 3% of the
total cells
Are part of the diffuse neuroendocrine
system.
Basal cells,
Small rounded cells on the basement
membrane. 11
Respiratory Epithelium

12
 The nose
Has two
parts:
Vestibule
Nasal cavity
(nasal
fossae)

13
 Vestibule The nose
Epithelial lining:
Anterior portion
lined by:
vibrissae, skin
sebaceous glands
sweat glands
Posterior potion
lined by:
nonkeratinized
stratified squamous
then pseudostratified
columnar epithelium 14
 The Nasal cavity
Divided into two regions:
Respiratory region
Olfactory region

Olfactory area superior

1/3 of cavities

15
Histology of Respiratory region of the
nasal cavity
Epithelium
Lined by pseudo stratified ciliated columnar/
respiratory epithelium with:
Ciliated columnar cells
Goblet cells - increase in number from
anterior to posterior
Basal cells
Lamina propria
complex vascular plexus
Swell bodies; extensive venous system for
countercurrent flow to warm air.
Lots of plasma cells, mast cells, lymphoid tissue

16
 Histology of olfactory region of the
nasal cavity
Lined by thicker pseudo stratified columnar
epithelium with;
1. Brush cells: the same as cells of respiratory
epithelium.
2. Olfactory receptor cells
. Spindle shaped bipolar neurons with central
round nucleus.
. Apex is modified dendrite with expanded
end - olfactory vesicle (olfactory knob
or bulb).
. Contains modified non motile cilia that
radiate parallel to the surface of the 17
 Histology of olfactory region of the
nasal cavity
2. Olfactory receptor cells...
Shaft of each cilia has two portions
A basal portion with the usual 9+1 pair
of the microtubules.
A distal longer and narrower portion
with 11 single microtubules.
Base is a thin unmyelinated axon
Make a bundle of fibres surrounded by
Schwann cells.
Give rise to 20 filaolfactory that pass
through cribriform plate of the ethemoid
bone to synapse in the olfactory bulb of
the brain. 18
Histology of olfactory region of the
nasal cavity

19
Histology of olfactory region of the
nasal cavity

20
 Histology of olfactory region of the
nasal cavity
3. Supporting (sustentacular) cells
Tall columnar cells with a narrow base and a
broad apex with long microvilli.
Contains Pale and oval nucleus
Contain a few pigment granules give the
olfactory epithelium a yellowish brown
colour
4. Basal cells small stem cells- located near
the basal lamina
Lamina propria - Rich plexus of the blood
vessels
Olfactory glands (gland of bowman): branched
21
 Histology of histology of the
paranasal sinuses
Lined by thinner pseudo stratified columnar
epithelium with fewer goblet cells.
Cilia beat toward the nasal cavity.
Thinner lamina propria with fewer glands
and no venous plexuses.

22
 Histology of larynx
Epithelium:
Pseudo stratified
columnar epithelium
lined:
False vocal cord
(vestibular folds)
Stratified squamous
nonkeratinized
epithelium lined:
True vocal cord
Anterior surface and
half of the posterior
surface of the epiglotis
Cilia beat toward the
pharynx.
23
Thinner lamina propria
 Histology of larynx
Below the epiglottis, the mucosa of the larynx
extends two pairs of folds bilaterally into
the lumen:
1. False vocal cord (vestibular folds)
Located upper and lined by respiratory
epithelium
Contains seromucous glands and areolar
tissue with MALT- (lymphoid nodules).
2. True vocal cord (vocal fold)
With stratified squamous nonkeratinized
epithelium.
Contain bundles of parallel elastic
24
fibers (vocal ligament) and large
 Histology of larynx
Show two
paired
folds:
False
vocal
cord
(vestibu
lar
folds)
True
The low-power micrograph shows the upper laryngeal vestibule (LV),
vocal
which is surrounded by seromucous glands (G). The lateral walls of this
cord
region bulge as a pair of broad folds, the vestibular folds (VF). lymphoid
nodules (L) , ventricle (V), below which is another pair of lateral folds, the
(vocal
vocal folds or cords (VC). vocalis muscle (VM). 25
 Histology of larynx
Has cartilage made
by
Hyaline
cartilage
Thyroid, cricoid
Most part of
the arytenoid
cartilages.
Elastic cartilage
Epiglotis
Corniculte
Cuniform
26
 Histology of Trachea

Histological layers
1. Mucosa
Epithelium
Lamina propria
2. Sub mucosa
3. Cartilage
&muscle layer
4. Adventitia

27
 Histology of Trachea
1. Mucosa
. Epithelium respiratory
epithelium
Cells include :-
Ciliated columnar cells ,
goblet cells, basal cells,
brush cells,
Neuroendocrine cell or
granule (kulchitsky) cells,
Clara cells( bronchiolar
cells) - surfactant
secretion
Thick basal lamina 28
 Histology of Trachea
2. Sub mucosa-
Loose connective tissue
Tracheal glands-Mixed
(serous &mucus) glands
Blood vessels and ducts
3. Cartilage &smooth
muscle layer-
C Shaped hyaline
cartilage covered by
perichondrium
Ends of cartilage
connected by smooth
muscles
29
4. Adventitia-fibro elastic
Histology of Trachea

Respiratory
epithelium (E)
Connective tissue
(CT) and
Seromucous glands
(G)
C-shaped rings of
hyaline cartilage
(C) covered by
perichondrium (P).
H&e.

30
31
 Bronchial Tree & Lung
The trachea divides into two
primary bronchi
Each primary bronchus
divides into lobar
(secondary) bronchi, two
on the left and three on the
right side.
The lobar bronchi give rise
to segmental bronchi
(tertiary bronchi) - further
give rise to smaller and
smaller bronchi-
bronchioles.
Each of these tertiary
32
bronchi, together with
 Histology of Bronchus

Principal bronchus
Same as trachea
Secondary /lobar bronchus
Same as trachea but
irregular hyaline cartilage
Tertiary /segmental
bronchus
Columnar epithelium
Patches of cartilage
3ry- bronchus

33
 Histology of Bronchiole
1 or less mm in diameter.
Epithelium: simple
columnar with
occasional goblet cells
to cuboidal with clara
cells.
Submucousa has no
gland
No cartilage
Divided into the
following three regions:
Primary 34
 Histology of Bronchiole
Primary
(larger)bronchiols
Lined by respiratory
epithelium but
gradually changing
to simple ciliated
columnar
epithelium.
Has scattered goblet
cells in the initial
segments.

35
 Histology of Bronchiole
Terminal bronchiole
Lined by simple non
cliated columnar
epithelium that
gradually change into
simple ciliated
cuboidal epithelium.
Lamina propria
contains elastic and
smooth muscle fibres.
No cartilage and gland
Respiratory bronchiole
Lined by simple
cuboidal epithelium
but has alveoli from 36
Terminal bronchiole and clara cells.
(A): cross-section shows that a terminal
bronchiole has only one or two layers of
smooth muscle cells. The epithelium
contains ciliated cuboidal cells and many
low columnar nonciliated cells. X300.

(B): the nonciliated clara cells with

bulging domes of apical cytoplasm contain
granules, as seen better in a plastic
section. Named for dr. Max clara, the
histologist who first described them in
1937. Important functions.
Surfactant
Produce enzymes that help break
down mucus locally.
Detoxifying enzyme in their smooth
ER- detoxifies potentially harmful
compounds in air.
Produce the secretory component for
the transfer of Iga into the
bronchiolar lumen
Lysozyme
Several cytokines that regulate local
inflammatory responses. X500 37
Distinguishing feature b/n
Bronchi and Bronchioles

Bronchioles
No glands
No cartilage
No goblet cells
Thick smooth muscle layer
Presence of Clara cells
Many elastic fibres

38
Summary- Changes as bronchi become smaller

A. Epithelium- pseudostratified ciliated columnar

epithelium in principal bronchi later simple ciliated
columnar, non-ciliated columnar and later cuboidal in
respiratory bronchioles
B. Glands- become fewer, and are absent in the walls
of bronchioles.
C. Cartilage- become irregular in shape, and are
progressively smaller and- It is absent in the walls
of bronchioles
D. Amount of muscle: in the bronchial wall increases
as the bronchi become smaller.
Spasm of this muscle constricts the bronchi and
can cause difficulty in breathing. Leads to a
disease called asthma. 39
 Summary of bronchial tree
Bronchu Tertiary Bronchi Respiratory
Trachea
s bronchus ole bronchiole
Epithelium Pseudost Columnar Cuboidal
ratified
Goblet cells ++ ++ + Absent
+++
Clara cells Absent Absent + +
Absent

Muscularis
Absent + ++ +++ +++
mucosae
Mucous ++ + Absent Absent
+++
glands
Cartilage ++ + Absent Absent
+++
Alveoli Absent Absent Absent +
Absent
40
 Histology of alveolar duct
Few cuboidal cell lining
between the alveoli
Lamina propria with:
Elastic and collagen
fibers.
Smooth muscle cells
as sphincters of the
alveoli.
Open into atria that
A. low magnification
Blead tomagnification
. high two or more
alveolar sacs bronchioles
respiratory
(RB)
alveolar ducts (AD) and
sacs (AS)
alveoli (A)
41
pulmonary artery (PA)
 Histology of alveolar atria
Are invested by dense and complex network
of elastic and reticular fibres, similar to
alveolar sacs and alveoli.

42
Histology of Alveoli
Are sac like out pocketing
present at the terminal end
of the bronchial tree
(respiratory bronchiols,
alveolar duct and sacs).
Form the parenchyma of lung.
About 200um in diameter, and
amount about 300 million in
the two lung making about 140
meter square
In section, they resemble a
honeycomb
Are separated by A. low magnification
B . high magnification
interalveolar septum lying respiratory bronchioles (RB) ,
alveolar ducts (AD) and sacs (AS) ,
43
between thin epithelial lining alveoli (A), pulmonary artery (PA),
Histology of interalveolar septum
Contain
Elastic fibres-enable the alveoli to expand
during inspiration and passively contract
during expiration.
Reticular fibres: support and prevent
overdistention of the alveoli
Capillary network that make the richest
capillary network in the body.
Occasionally it contains fibroblasts,
macrophages and mast cells.

44
 Histology of interalveolar septum
Also Contains pores(alveolar pores of
kohn)
Present 1-6 , or more in each alveolus.
Are about 10-5um in diameter
Help in passage of air from one alveolus
to another, Thus equalizing pressure in
the alveoli
Enable collateral circulation.

45
 Cells of the interalveolar septa
1. Type I Pneumocytes

2. Type II Pneumocytes

3. Endothelial cells of the capillaries

4. Macrophages or Dust cells

5. Interstitial cells

46
 Type I Pneumocytes(pulmonary
epithelium or squamous alveolar
cells)
Highly squamous cells with about 0.2um in
diameter.
Organelles cluster around nucleus.
Are uniting by tight junctions and have
desmosomes
preventing leakage of blood from
capillaries to the alveolar lumen - form
blood air barrier
Make 8-10% of cells of the inter alveolar cells
but lines 95 -97% of alveolar surface.
Show pinocytotic vesicle (may role in 47
Type I Pneumocytes

48
Type II pneumocytes (great alveolar or
septal cells)
Simple cuboidal secretory cells with short
microvilli as group of 2 or 3 cells.
Located near the angles b/n neighboring
alveolar septum, bulging into alveolar lumen
b/n type I pneumocytes or deep to them.
Has irregular nucleus, and junctional complex
with type I pneumocytes
Make 12-16% of interalveolar septum and
lines 3-5% of the alveolar surface.
Contains several layer of secretory granules
called multi lamellar bodies.
49
 Type II Alveolar or Type II pneumocytes

Multi lamellar bodies

Are cytoplasmic inclusions made up of
phospholipid, GAG and proteins which
combines with other chemicals to form
surfactant & then ooze out of the cell by
exocytosis.
Pulmonary surfactant is the fluid that
spreads over the alveolar surface
It has bactericidal properties
These cells can multiply to replace
damaged cells.
50
Type I and II Pneumocytes, capillaries and Dust
cells

51
 Pulmonary Surfactant
Contains phospholipids, proteins and
glycosaminoglycans, reduces the surface tension
and prevents collapse of the alveolus during
expiration.
The reduced surface tension in the alveoli
decreases the force that is needed to inflate
alveoli during inspiration.
Therefore surfactant stabilizes the alveolar
diameters, facilitates their expansion and
prevents their collapse by minimizing the
collapsing forces
Is constantly renewed.
Removed from the surface by type I pneumocytes
and macrophages 52
 Cells of the interaveolar septa
3. Endothelial cells of the capillaries
Account for about 30% of the cells of inter
alveolar septum.
Are continuous type.

53
 Cells of the interaveolar septa
4. Interstital cells
Different cells of making
about 36% of cells in the
interalveolar septum
Includes
fibroblast that deposit
collagen type I and III.
Mast cells
Contractile cells
(myofibroblasts) that are
bound to basal surface of
alveolar epithelium and
when contract lower the 54
volume of the alveolar
 Cells of the interaveolar septa

4. Alveolar
Macrophages or
Dust cells

Make about 10% of the

cells of interalveolar
septum.

Main function is to clean

the alveoli of invading
microorganisms and
inhaled particulate
matter by phagocytosis 55
 Blood vessels in the
respiratory system
A. Pulmonary vessels (functional vessels)
B. Systemic vessels (nutrient vessels)

56
 Blood vessels in the
respiratory system
A.Pulmonary vessels (functional
vessels)
. Pulmonary arteries
Accompany bronchial tree as far as
respiratory bronchioles
Make capillary network in the interalveolar
septum
Have more smooth muscle and elastic
fibers than the pulmonary veins.
Have internal elastic membrane, which
absent from pulmonary veins.
57
 Blood vessels in the
respiratory system
A.Pulmonary vessels (functional
vessels)
. Pulmonary veins
Run in the pleura and intersegmental
connective tissue independently of the
arteries

58
 Blood vessels in the
respiratory system
B. Systemic vessels (nutrient vessels)
By bronchial arteries
Supply the bronchial tree as far as the
respiratory bronchioles, pleura and
interlobular connective tissue.
Although bronchial veins are present,
most of the blood is drained back by
pulmonary veins for there are
anastomoses between terminal
branches of bronchial and pulmonary
arteries and between small bronchial
and pulmonary veins.
59
 Lymphatic vessels
Found as lymphatics of pleura and
pulmonary parenchyma, with numerous
communications between them.
Pulmonary lymphatics are associated
with bronchi, pulmonary arteries and
pulmonary veins.
Not found in the terminal portion
beyond alveolar ducts.

60
 Blood air barrier:
Is that region of the interalveolar septum that
is traversed by O2 and CO2 as these gases go
from the blood to the lumen of the alveolus
,and vice versa.
Made by the following structure:
1. Surfactant
2. Type I pneumocytes
3. Endothelial cells of the continuous caillary.
4. Based laminae of type i pneumocytes and
endothelial cells of the capillary 61
Alveoli and the blood-air barrier.
(a): Diagram shows the relationship between capillaries and two or more saclike alveoli.
(b): The air-blood barrier consists of an alveolar type I cell, a capillary endothelial cell, and
their fused basement membranes. Oxygen diffuses from alveolar air into capillary blood
and carbon dioxide moves in the opposite direction. The inner lining of alveoli is covered by
a layer of surfactant, not depicted here, which lowers fluid surface tension and helps 62
prevent collapse of alveoli.
 Defense mechanism in the
respiratory system
Bigger particles with diameter of:
More than 10um are retained by the
coares hairs nasal cavity.
2-10um are trapped in the mucous coated
ciliated epithelium which are expectorated
or swallowed following cough.
Smaller particles are removed by
alveolar macrophages and the
immunological processes of the lymphoid
tissue of the bronchi.
63
 Histology of the
pleura
A thin layer of the
mesothelium Mesothelium
(M)
covered connective Visceral
pleura
covering
tissue containing: alveoli (A)
Blood vessels
(V) and
Fibroblasts. lymphatics (L)

Collagen and
several layers of
the elastic fibres.
Capillaries and
lymphatics.
64
Part two
Development of Respiratory
System

65
 OBJECTIVES
At the end of this session you should be
able to :
Describe the development of the
laryngeotracheal (respiratory)
diverticulum.

Identify the development of the larynx.

Identify the development of the trachea.

Identify the development of the bronchi
& lungs.

Describe the periods of the maturation of

66
 Respiratory System
Upper respiratory
tract: will be
described later
Nose
Nasal cavity &
paranasal sinuses
Pharynx
Lower respiratory
tract:
Larynx
Trachea
Bronchi
Lungs 67
 Development of the Lower
Respiratory Tract
RESPIRATORY
PRIMORDIUM
Begins to form during the
4th week as laryngotracheal
groove from the caudal
part of the ventral wall of
the primitive pharynx
At end of the 4th week:
the laryngotracheal groove
has evaginated to form a
pouch like
laryngotracheal
diverticulum
68
 RESPIRATORY PRIMORDIUM

A longitudinal tracheo-
esophageal septum
develops and divides the
foregut into:
Dorsal portion:
primordium of the
oropharynx and
esophagus
Ventral portion:
primordium of larynx,
trachea, bronchi and
lungs 69
 RESPIRATORY PRIMORDIUM
The proximal part of the
respiratory diverticulum
remains tubular and forms:
Larynx
Trachea
The distal end of the
diverticulum dilates to
form:
Lung bud, also divides
to give rise to:
2 lung buds
(primary
bronchial buds)
70
 RESPIRATORY PRIMORDIUM

Successive stages in the development of the tracheoesophageal septum during the fourth and fifth Wk

A to C, Lateral views of the caudal part of the primordial pharynx showing the laryngotracheal
diverticulum and partitioning of the foregut into the esophagus and laryngotracheal tube.

D to F, Transverse sections illustrating formation of the tracheoesophageal septum and showing

how it separates the foregut into the laryngotracheal tube and esophagus. The arrows indicate
cellular changes resulting from growth.
71
 RESPIRATORY PRIMORDIUM

The endoderm lining the laryngotracheal

diverticulum gives rise to:
Epithelium
Glands of the respiratory tract
The surrounding splanchnic mesoderm
gives rise to:
Connective tissue
Cartilage
Smooth muscles of the respiratory tract

72
 Development of the Larynx
The opening of the laryngotracheal
diverticulum into the primitive foregut
becomes the laryngeal orifice.
The epithelium & glands are derived from
endoderm.
Laryngeal muscles develop from
myoblasts in the 4th & 6th pairs of
pharyngeal arches.
Laryngeal cartilages develop from
mesenchyme that is derived from neural
crest cells in 4th & 6th pairs of
pharyngeal arches. 73
Successive stages in the development of
the larynx.

A, At 4 weeks.
B, At 5 weeks.

74
C, At 6 weeks.
 Development of Epiglottis
It develops from the
caudal part of the
hypopharyngeal
eminence.
A, At 4 weeks. B, At
Hypopharyngeal eminence 5 weeks.
is a swelling formed by the
proliferation of
mesoderm in the floor
of the pharynx. C, At 6 weeks.
D, At 10 weeks.
The rostral part of this Growth of the larynx
and epiglottis is rapid
eminence forms the
during the first three
posterior third or years after birth.
pharyngeal part of the By this time the 75
Recanalization of larynx
During 10th week The
laryngeal epithelium
undergoes rapid
proliferation resulting in
temporary occlusion of
the laryngeal lumen
Then by dissolution of
cell it become canalized.
Laterally: Laryngeal
ventricles, vocal folds
and vestibular folds are
formed during
recanalization. 76
 Anomalies of larynx
Laryngeal atresia: results from failure of
recanalization of the larynx, which causes
obstruction of the upper fetal airway-congenital
high airway obstruction syndrome. As a result:
Airways become dilated,
Lungs are enlarged and echogenic (capable of
producing echoes during ultrasound imaging
studies because they are filled with fluid)
Diaphragm is either flattened or inverted
Fetal ascites and/or hydrops (accumulation of
serous fluid in the intracellular spaces causing
77
 Development of the Trachea
Endodermal lining of the
laryngotracheal tube give
rise to:
Glands of the trachea and
pulmonary epithelium.
Surrounding
mesodermal
(mesenchymal) lining
give raise to:
Cartilages
Connective tissue
Muscles of the trachea.
78
 Development of the Trachea

Transverse sections through the laryngotracheal tube illustrating

progressive stages in the development of the trachea.
A, At 4 weeks. B, At 10 weeks. C, At 11 weeks
Note that endoderm of the tube gives rise to the epithelium and
glands of the trachea and that mesenchyme surrounding the tube
forms the connective tissue, muscle, and cartilage.
79
D, Photomicrograph of a transverse section of the developing
Tracheoesophageal Fistula A fistula (abnormal passage)

Results from incomplete division of the cranial part

of the foregut into respiratory and esophageal parts
during the fourth week and can be associated
with esophageal atresia.
As result:
Infants cannot swallow so they frequently drool
saliva at rest and immediately regurgitate milk
when fed.
Gastric and intestinal contents may also reflux
from the stomach into the trachea and lungs.
This refluxed acid - can cause pneumonitis
(inflammation of the lungs) leading to
respiratory compromise. 80
Tracheoesophageal Fistula A fistula (abnormal passage)

Polyhydramnios is often associated with esophageal

atresia.
The excess amniotic fluid develops because fluid
cannot pass to the stomach and intestines for
absorption and subsequent transfer through the
placenta to the mother's blood for disposal.

Tracheoesophageal fistula (TEF) in a 17-week male fetus. The upper esophageal

segment ends blindly (pointer). B, Contrast radiograph of a newborn
81 infant with TEF.
Note the communication (arrow) between the esophagus (E) and trachea (T). (A, From
 Anomalies of the trachea

Tracheoesophageal fistula (TEF) in a 17-week male fetus. The upper

esophageal segment ends blindly (pointer). B, Contrast radiograph
of a newborn infant with TEF. Note the communication (arrow)
82
between the esophagus (E) and trachea (T). (A, From Kalousek DK,
Laryngotracheoesophageal Cleft
Uncommonly, the larynx and upper trachea
may fail to separate completely from the
esophagus.
This results in a persistent connection of
variable lengths between these normally
separated structures.
Symptoms of this congenital anomaly are
similar to those of tracheoesophageal fistula
because of aspiration into the lungs, but
aphonia (absence of voice) is a
distinguishing feature.

83
Anomalies of the trachia

84
 Development of the Bronchi & Lungs
During 4th wk
The respiratory bud (lung bud)
developed at the caudal end of
the laryngotracheal diverticulum -
Soon it divides into 2 primary
bronchial buds
Bronchial buds grow laterally
into the pericardio-peritoneal
canals (part of the
intraembryonic celome), the
primordia of pleural cavities
Together with the surrounding
splanchnic mesenchyme, the
bronchial buds differentiate into 85
 Development of the Bronchi & Lungs

Early in the fifth week,

The connection of each bronchial bud with
the trachea enlarges to form the primordia
of main bronchi

86
 Development of the Bronchi & Lungs
The right main bronchus is
slightly larger than the left
one and is oriented more
vertically
The embryonic
relationship persists in the
adult.
The main bronchi
subdivide into secondary
and tertiary
(segmental) bronchi
which give rise to further
branches. 87
 Development of the Bronchi & Lungs

By 7th week :
segmental bronchi, 10 in
right lung and 8 or 9 in
the left lung begin to
form.
Each segmental
bronchus with its
surrounding mass of
mesenchyme is the
primordium of a
bronchopulmonary
segment. 88
Successive stages in the development of the
bronchial buds, bronchi, and lungs. 89
 Development of the Bronchi & Lungs
By 24 weeks, about 17 orders of branches
have formed and respiratory bronchioles
have developed.
An additional seven orders of airways develop
after
As the lungs develop
birth.
they acquire a layer
of:
Visceral pleura
derived- from
splanchnic
mesenchyme.
Parietal pleura
derived from the
somatic 90
 Maturation of the Lungs

Is divided into 4 periods:

1. Pseudoglandular period (6 - 16
weeks)
2. Canalicular period (16 - 26 weeks)
3. Terminal sac period (26 weeks -
birth)
4. Alveolar (late fetal period 8years)

These periods overlap each other because91

 Pseudoglandular Period (6-16 weeks)

Developing lungs
somewhat histologically
resembles an exocrine
gland.
By 16 weeks all major
elements of the lung have
formed except those
involved with gas
exchange (alveoli).
Respiration is NOT
possible.
92
 Canalicular Period (16-26 weeks)

Lung tissue becomes highly

vascular.
Lumina of bronchi and
terminal bronchioles become
larger.
By 24 weeks each terminal
bronchiole has given rise to Fetus born at the
respiratory bronchioles. end of this
Respiratory bronchioles period may
survive if given
divide into alveolar ducts. intensive care
Some thin-walled terminal (but usually die
because of the
sacs (primordial alveoli) immaturity of
develop at the end of respiratory
93
as
 Terminal Sac Period (26 weeks - birth)

Many more terminal sacs

develop.
Capillaries begin to bulge into
developing alveoli.
The epithelial cells of the
alveoli and the endothelial cells
of the capillaries come in
intimate contact and establish
the blood-air barrier.
Adequate gas exchange can
occur which allows the
prematurely born fetus to
survive 94
 Terminal Sac Period (26 weeks -
birth)
By 26 weeks, the terminal sacs are lined by:
Squamous type I pneumocytes and type II
pneumocytes
Surfactant production begins by 20 weeks, but it is
present in only small amounts in premature infants.
It does not reach adequate levels until the late
fetal period.
Sufficient terminal sacs, pulmonary
vasculature & surfactant are critical for the
survival of a prematurely born infants.
Fetuses born prematurely at 24-26 weeks may
suffer from respiratory distress due to 95
 Terminal Sac Period (26 weeks - birth)
Surfactant
Forms as a monomolecular film over the
internal walls of the alveolar sacs and
counteracts surface tension forces at the air-
alveolar interface.
This facilitates expansion of the saccules
(primordial alveoli) by preventing
atelectasis (collapse of saccules during
exhalation).

96
 Alveolar Period (32 weeks 8 years)
At the beginning: each
respiratory bronchiole terminates
in a cluster of thin-walled
terminal saccules, separated
from one another by loose
connective tissue.
The epithelial lining of the
terminal sacs attenuates to an
extremely thin squamous
epithelial layer.
By the late fetal period, the lungs
are capable of respiration
because the alveolocapillary
membrane (pulmonary diffusion 97
 Alveolar Period (32 weeks 8 years)
The transition from
dependence on the
placenta for gas exchange
to autonomous gas
exchange requires the
following adaptive changes in
the lungs:
Production of surfactant in
the alveolar sacs
Transformation of the lungs
from secretory into gas
exchanging organs
Establishment of parallel
pulmonary and systemic 98
 Alveolar Period (32 weeks 8 years)
Characteristic mature alveoli do not form until after birth.
95% of alveoli develop postnatally.
About 150 million alveoli, one half of the adult number
are present in the lungs of a full-term newborn infant.
Most increase in the size of the lungs results from an
increase in the number of respiratory bronchioles and
primordial alveoli. Rather than from an increase in the
size of the alveoli.
The lungs of newborn infants are denser than adult lungs
From 3-8 year or so, the number of immature alveoli
continues to increase.
Unlike mature alveoli, immature alveoli have the
potential for forming additional primordial alveoli.
By about the eighth year, the adult complement of 300
million alveoli is present. 99
Diagrammatic sketches of histologic sections illustrating the stages of lung
development. A and B, Early stages of lung development. C and D, Note that
the alveolocapillary membrane is thin and that some capillaries bulge into
100
the terminal sacs and alveoli.
 Lungs of a Newborn
Fresh healthy lung always contains some air
(lungs float in water). Diseased lung may
contain some fluid and may not float (may sink).
Lungs of a stillborn infant are firm, contain fluid
and may sink in water.

101
Removal of amniotic fluid
At birth, the lungs are approximately half-
filled with fluid derived from the amniotic
cavity, lungs, and tracheal glands.
The fluid in the lungs is cleared at birth
by three routes:
Through the mouth and nose by pressure
on the fetal thorax during vaginal delivery
Into the pulmonary arteries, veins, and
capillaries
Into the lymphatics

102
Three are Factors important for normal
lung development
Adequate thoracic space for lung growth.
Fetal breathing movements.
Adequate amniotic fluid volume.

103
 Developmental anomalies
Oligohydramnios and lung development
When oligohydramnios (insufficient amount
of amniotic fluid) is severe and chronic
because of amniotic fluid leakage or
decreased production
Lung development is retarded and severe
pulmonary hypoplasia results from
restriction of the fetal thorax.

104
 Developmental anomalies
Respiratory distress syndrome
Is an acute lung disease caused by surfactant
deficiency, which leads to alveolar collapse
and noncompliant lungs.
Risk increases with degree of prematurity.
As the baby's lung function decreases, less
oxygen is taken in and more carbon dioxide
builds up in the blood.
This can lead to increased acid in the blood
called acidosis, a condition that can affect
other body organs.
105
 Developmental anomalies
Congenital Lung Cysts
Cysts (filled with fluid or air) are thought to
be formed by the dilation of terminal
bronchi.
They probably result from a disturbance in
bronchial development during late fetal life.
If several cysts are present, the lungs have
a honeycomb appearance on radiographs.
Congenital lung cysts are usually located at
the periphery of the lung.

106
Congenital Lung Cysts

107
 Developmental anomalies
Agenesis of Lungs
Absence of the lungs results from failure of
the respiratory bud to develop.
Agenesis of one lung is more common
than bilateral agenesis, but both conditions
are rare.
Unilateral pulmonary agenesis is
compatible with life.
The heart and other mediastinal structures
are shifted to the affected side, and the
existing lung is hyperexpanded.
108
 Developmental anomalies
Accessory Lung
A small accessory lung (pulmonary
sequestration) is very uncommon.
It is almost always located at the base of
the left lung.
It does not communicate with the
tracheobronchial tree, and its blood supply
is usually systemic rather than pulmonary
in origin.

109
 Quiz
1. Write basic distinguishing feature of
bronchioles
2. Describe the basic adaptive changes occurs
during transfer of gas exchange from
dependence on placenta to autonomic gas
exchange in the lungs
3. Describe the histological feature of larynx
4. Describe basic changes occurs during
ramification of the bronchial tree

110