DEVELOPMENT OF RESPIRATORY SYSTEM AND ITS
ANOMALIES
LEARNING OBJECTIVES:
1. Enumerate the different Parts of Respiratory System
2. Name the Different Parts of Foregut
3. Discuss the formation of laryngo- tracheal tube
4. Discuss the formation of Lung Bud
5. Describe the Branches of Bronchi
6. Discuss the different Stages of development of Lung
7. Describe Maturation of Lung
8. Enumerate the congenital errors during development
DIFFERENTIATION (ORGANOGENESIS)
• ORGanogenesis is the formation of the organs. Arises from the
layering of cells that occurs during gastrula stage
• The layers are germ layers; they have specific fates in the
developing embryo:
– Endoderm
• The innermost layer
• Goes on to form the gut
– Mesoderm
• In the middle
• Goes on to form the muscles, circulatory system,
blood and many different organs
– Ectoderm
• The outermost
• Goes on to form the skin and nervous system
•
Differentiation of Primary Germ Layers (from the gastrula)
Ectoderm
Mesoderm
Endoderm
Nervous system
Skeleton
Digestive tract
Epidermis of skin Muscles
Respiratory
system
Circulatory system Liver, pancreas
Gonads
Bladder
FUNCTIONAL DIVISION OF RESPIRATORY SYSTEM
Functionally the Respiratory System is divided into two parts:
 Conducting Part
 Respiratory Part
CONDUCTING PART:
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Nostrils Vestibule
Nasal Cavity
Nasopharynx
Oropharynx
Laryngopharynx
Larynx,
Trachea
Principal Bronchi
Secondary Bronchi
Segmental Bronchi Upto Terminal Bronchioles
RESPIRATORY PART
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Respiratory Bronchioles
Alveolar Duct
Alveolar Sac,
Alveoli
Developmental Division of Respiratory
System
Developmentally the Respiratory System is divided into two parts:
1. Upper Part of Respiratory System
2. Lower Part of Respiratory System
Upper part of respiratory system
 Extends from nose to larynx
 Develops from the Pharyngeal Apparatus which is a part of Head
& Neck
Lower Part of Respiratory System
 Extends below the Larynx up to lung alveoli
 This part develops From the Foregut
DEVELOPMENT OF THE NOSE
 Related to formation of face
 Nasal placodes- primordia of nose and nasal cavities
 Proliferation of mesenchyme in margins of nasal
placode medial and lateral nasal prominences
 Nasal pit- primordia of nares and nasal cavities
 Medial nasal prominences form the tip of the
nose, nasal septum, and the intermaxillary
segment
 Lateral nasal prominences form the sides (alae) of the nose
 Frontonasal prominence forms the bridge of the nose
LARYNX
GERM LAYER ORIGIN
 Mesoderm- cartilages and muscles (4th & 6th pharyngeal
arches, thyroid , cricoid and
Arytenoid)
 Endoderm- internal lining of the
epithelium
 Transformation of mesenchyme to
cartilaginous components produces T
shaped laryngeal orifice
 Epithelium- endoderm
 Thyroid, cricoid, arytenoid cartilages and muscles from 4th and
6th branchial arches
 Transformation of mesenchyme to cartilaginous components
produces T shaped laryngeal orifice
Different Parts of Foregut
The foregut can be divided into three parts:
1. The first part lies ventral to the developing
brain, and forms the primitive pharynx,
which has the branchial arches associated
with it.
2. The second part lies dorsal to the heart,
and forms the lung bud and the
oesophagus.
3. The third part lies dorsal to the septum transversum and forms
the stomach and other related gastro-intestinal structures.
Respiratory System is derived from Second Part of Foregut
a. It begins to develop in the beginning of the fourth week (day 22)
b. It begins as a laryngo- tracheal groove on the ventral aspect of
the foregut, which deepens and forms a repiratory diverticulum.
c. Separates from the oesophagus
Development of Lung Bud
The respiratory diverticulum's bifurcates into right and left
bronchial buds on day 26-28.
Division of Lung Bud
Asymmetric branching occurs during the following 2 weeks to form
secondary bronchi:
3 on the right and 2 on the left forming the main divisions of the
bronchial tree.
 The lung bud and its subsequent branches are of endodermal
origin.
 They give rise to the epithelium lining all the respiratory
passages, the alveoli and the associated glands.
 The surrounding mesoderm, the splanchnopleure, gives rise to
all the supporting structures: the connective tissue, cartilage,
muscle and blood vessels.
Branching of Bronchi
 The pattern of branching is regulated by
the surrounding mesoderm.
 The mesoderm surrounding the trachea
inhibits branching whereas the
mesoderm surrounding the bronchi
stimulates branching.
 Transplantation of part of the bronchial
mesoderm to replace part of the
tracheal mesoderm forms an ectopic
lobe of the lung arising directly from the
trachea. Transplantation of part of the tracheal
mesoderm to replace part of the bronchial
mesoderm suppresses the formation of a lobe.
During weeks 7 to 16 branching occurs about 14
times to the level of terminal bronchioles. At this
stage there are no alveoli. The foetal lung during this
period is described as the glandular stage because
the terminal bronchioles resemble glandular acini.
The bronchi, containing cartilage in their walls,
identify the sections as foetal lung.
Stages of Development of the Lungs
1. The Pseudo-glandular stage – weeks 6 to 16 – there is
repeated branching about 14 times) to the level of the terminal
bronchioles.
2. The canalicular stage – weeks 16 to 26 – the respiratory
bronchioles develop
3. The saccular stage – weeks 26 to 36 Development (the
primary alveoli develop).
4. The alveolar stage – weeks 36 to 40 – the alveoli mature:
Pseudoglandular phase (6 to 16 Weeks)
At this stage the lungs resemble the development of a
Exocrine Gland.
By the end of 16 weeks all the major elements of the
lung development have formed except those involved
with gas exchange. Respiration is not possible, hence
fetuses born during this period are unable to survive
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.
Saccular phase
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.
Saccular phase
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
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,1/3 of the roughly 300
million alveoli should be fully developed. The alveoli,
though, are only present 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.
Maturation of Lung
Characteristic mature alveoli do not form until after birth, about 95%
of alveoli develop postnatally. Before birth the primordial alveoli
appear as small bulges on the wall of respiratory bronchioles and
terminal saccules. From 3rd to 8th the number of immature alveoli
continues to increase. The major mechanism for increasing number
of alveoli is the formation of connective tissue septa that subdivide
existing primordial alveoli. About 50 million alveoli, one sixth of the
adult number are present in the lungs of full term newborn infant. By
about the eight year 300 million alveoli present in lungs
Breathing movements occur before birth, exerting sufficient force to
cause aspiration of some of amniotic fluid into lung. These movement
are essential for normal development of lung. Fetal breathing
movement, which increase as the time delivery approaches, probably
condition the respiratory muscles. These movements stimulate lung
development, possibly by creating a pressure gradient between lungs
and amniotic fluid.
Lung Expansion at Birth
At birth about half the lungs are filled with fluid, derived from the
amniotic cavity, lung and tracheal glands. Aeration of lungs at birth
occur due rapid replacement of intra-alveolar fluid by air. The fluid in
the lungs is cleared at birth by three routes:
• Through mouth and nose by pressure on thorax during delivery
• Into pulmonary capillaries
• Into lymphatic and pulmonary Arteries and Veins
Factors Important for normal Lung Development
• Adequate thoracic space for lung growth
• Fetal breathing movements
• Adequate amniotic fluid volume
Developmental Anomalies of Respiratory System
• Esophageal Artesia
• Trcheo-Esophageal Fistula
• Congenital Diaphragmatic Hernia
• Pulmonary Hypoplasia
ESOPHAGEAL ATRESIA
• Esophageal atresia is a congenital anomaly
• Affects the alimentary tract
• Esophagus ends in a blind-ended pouch
rather than connecting normally to the
stomach
INCIDENCE
• Occurs in approximately 1 in 4425 live births
• May or may not occur with TEF
• Isolated variant is rare
ESOPHAGEAL ATRESIA
PATHOPHYSIOLOGY
• failure of the esophagus to develop as a continuous passage .
• ends as a blind pouch.
• failure of the recanalization of the esophagus during the
eighth week of development ;no tracheoesophageal fistula
• When associated with fistula there is deviation of
tracheoesophageal septum posteriorly
• Immediately diagnosed after birth
• Should be promptly treated
CONGENITAL TRACHEOESOPHAGEAL FISTULA
• A fistula is an abnormal connection running either between two tubes or
between a tube and a surface
• TEF is an abnormal communication between
trachea and oesophagus
• arises due to failed fusion of the tracheoesophageal
ridges during the third week of embryological
development.
• often found in association with other congenital
anomalies
• can be of diverse morphology and anatomical location,
• Esophageal atresia results if the tracheoesophageal
septum is deviated posteriorly.
•
causes incomplete separation of the
esophagus from the laryngotracheal tube and results in
tracheoesophageal fistula.
TYPES OF TEF
• Proximal esophageal atresia (esophagus continuous with
the mouth ending in a blind loop superior to the sternal
angle with a distal esophagus arising from the lower
trachea or carina.
•
(Most common, up to 90% of cases--sometimes called a
Type C fistula.)
Proximal and distal esophageal bud--a normal esophagus
•
with a missing mid-segment. (Type A.)
•Proximal esophageal termination on the lower trachea or carina with distal
esophagus arising from the carina. (Type D.) If the two segments of
esophagus communicate, this is termed an H-type fistula
due to its resemblance to the letter H.
•Proximal esophageal termination on the lower trachea with
distal esophageal bud. (Type B.)
TRACHEOESOPHAGEAL FISTULA
• Maybe associated with other congenital
•
anomalies
•
called the VACTREL
•
(vertebral defect, anal
•
atresia, cardiac anomalies,
•
tracheoesophageal fistula,
•
renal anomalies,
•
esophageal atresia, limb
•
deformities)
TRACHEO-ESOPHAGEAL FISTULA
Different Types
DIAGNOSIS ANDCLINICAL
PRESENTATION
• This condition is visible, after about 26 weeks, on an ultrasound, may be
detected soon after birth in a newborn by copious salivation
• choking,
• Coughing
• cyanosis
• Gastric distention
• All symptoms coincident with the
onset of feeding .
COMPLICATION
Aspiration pneumonia when attempt to feed
the milk collects in the blind pouch and overflows into the trachea
and lungs.
Gastric acid aspiration as fistula between the lower esophagus and
trachea may allow stomach acid to flow into the lungs and cause
damage .
TREATMENT
• vary depending on its severity
•
The most immediate and effective treatment in the majority of cases is a
surgical repair to close the fistula/s and reconnect the two ends of the
esophagus to each other
• .When gap is too large, a gastrostomy is performed, allowing tube
feedings into the stomach through the abdominal wall.
• Followed by repairing of oesophagus by interposing a segment of gut
between the upper and lower segments months or years later,
HYALINE MEMBRANE DISEASE
Respiratory Distress Syndrome RDS
 Seen among premature infants
 Insufficient surfactant resulting in high membrane
tension thus collapse of alveoli
 Many hyaline membrane and lamellar bodies
present in collapsed alveoli
 Incidence - RDS occurs primarily in the immature
lung.
(1) 60 % of cases occur in infants born at less than 28 weeks’ gestation
(2) 5 % of cases occur in infants born at less than 37 weeks’ gestation
HYALINE MEMBRANE DISEASE
Respiratory Distress Syndrome
CLINICAL FINDINGS
• Onset Usually less than 2-5 hours after birth
• Increases in severity from 24 to 48
hours
•
gradual improvement after 48-72 hours
• Abnormal retraction of chest wall
• Cyanosis
• Expiratory grunting
• Increased respiratory rate
PULMONARY HYPOPLASIA
Pulmonary hypoplasia results when lungs are
compressed by abnormally positioned
abdominal viscera and cannot develop
normally or expand at birth .It is commonly
caused by congenital posterolateral
diaphragmatic hernia .
CONGENITAL DIAPHRAGMATIC
HERNIA
• Failure of the pleuroperitoneal foramen (foramen of
Bochdalek) to close allows viscera into thorax. Intestine,
stomach or spleen can enter the pleural cavity,
compressing the lung.