.

Development of the Respiratory Diverticulum (Early

Stage)

• Week 4: The respiratory system begins to develop during the fourth week of embryonic
development as an outgrowth of the foregut. This outgrowth, known as the respiratory
diverticulum or laryngotracheal groove, forms from the ventral wall of the foregut, just below
the pharynx.

• Formation of the Trachea: The respiratory diverticulum elongates and bifurcates into two
bronchial buds, which will eventually form the left and right main bronchi.

2. Development of the Trachea and Bronchi (Weeks 4-7)

• Week 4-5: The respiratory diverticulum elongates and divides into two buds (primary bronchial
buds), which will form the trachea and the main bronchi. These buds grow into the surrounding
mesoderm, which forms the tissues of the lungs.

• Week 5-6: The bronchial buds divide further into secondary bronchi (for each lung lobe). For
instance, the right bronchial bud divides into three secondary bronchi (for the three right lung
lobes), and the left bud divides into two (for the two left lung lobes).

• Week 6-7: The formation of tertiary (segmental) bronchi begins, establishing the basic bronchial
structure of the developing lungs.

3. Development of Bronchial Tree (Weeks 7-16)

• Weeks 7-16: The process of bronchial branching continues, resulting in the development of the
bronchial tree. The primary, secondary, and tertiary bronchi will give rise to increasingly smaller
branches, eventually forming the terminal bronchioles.

• Pseudoglandular Stage: By the end of this period (around 16 weeks), the lungs have developed a
rudimentary bronchial tree, but the respiratory zones (where gas exchange occurs) are not yet
formed.

4. Canalicular Stage (Weeks 16-26)

• Week 16-24: This period is characterized by the development of terminal bronchioles and the
beginning of alveolar ducts. The lung tissue becomes vascularized, allowing for the formation of
capillaries around the airways.

• Week 24: The terminal bronchioles will start to differentiate into respiratory bronchioles.

• Surfactant Production: Around this time, surfactant (a substance that reduces surface tension in
the lungs) begins to be produced, an essential step for lung function after birth.

5. Saccular Stage (Weeks 26-36)

• Week 26-36: During this stage, the respiratory bronchioles further develop into alveolar sacs,
resembling the final structure of the alveoli, where gas exchange will occur. The number of
capillaries around these structures increases dramatically.
 • Maturation of Alveoli: The alveolar ducts lead to the formation of primitive alveoli that begin to
resemble the mature lung structure but are not yet fully functional.

6. Alveolar Stage (Week 36 to Birth)

• Week 36-Birth: The alveolar stage involves the formation of mature alveoli. By the time of birth,
the lungs will have a sufficient number of alveoli for gas exchange. However, full lung function
will continue to mature postnatally.

• Alveolar Growth: After birth, alveolar growth continues, with the lungs reaching their full
functional capacity around the age of 2 years.

Key Points:

• Lung maturation is a gradual process that continues throughout fetal development and beyond
birth. The development of body cavities and diaphragm during embryogenesis is a crucial part of
forming the body's internal structure, and their anomalies can lead to various congenital
conditions. These processes are well-documented in Langman’s Medical Embryology, which
describes the development of the body cavities and diaphragm in detail. Here's a breakdown of
their formation and potential anomalies:

• Development of Body Cavities

• Formation of the Body Cavities:

• Pre-cardiac and intra-embryonic coelom: The body cavities begin as a single, horseshoe-shaped
space called the intra-embryonic coelom, which is located within the mesoderm during the early
stages of development.

• As development progresses, the intra-embryonic coelom divides into three main cavities:

• Pericardial cavity (around the heart)

• Pleural cavities (around the lungs)

• Peritoneal cavity (around the abdominal organs)

• These cavities are formed as the lateral plate mesoderm splits into two layers: the somatic
(parietal) layer and the splanchnic (visceral) layer. The space between these layers becomes the
body cavities.

• Separation of Cavities:

• During the 4th and 5th weeks of development, the septum transversum and other mesodermal
structures help to partition the coelom into the thoracic cavity and abdominal cavity, creating
the diaphragm as a partition between these two.

• Development of the Diaphragm

• The diaphragm develops primarily from four structures:

• Septum transversum: This mesodermal tissue, located at the level of the future cervical region,
forms the central tendon of the diaphragm.

• Pleuroperitoneal membranes: These membranes grow toward the septum transversum from
the sides of the developing body, closing the gaps between the developing thoracic and
abdominal cavities.

• Dorsal mesentery of the esophagus: This part contributes the muscle fibers to the diaphragm,
helping form its muscular component.

• Body wall: Muscular components from the body wall, particularly the cervical myotomes,
contribute to the peripheral muscular parts of the diaphragm.

• Diaphragm and Its Anomalies

• Normal Formation:

• As the diaphragm forms, it separates the thoracic cavity (which houses the lungs and heart) from
the abdominal cavity (housing the digestive and other organs). This separation ensures proper
development and function of the organs in each cavity.

• Anomalies in Diaphragm Development:

• Congenital Diaphragmatic Hernia (CDH):

• This is one of the most common anomalies associated with the diaphragm. It occurs when there
is incomplete closure of the pleuroperitoneal membranes, allowing abdominal organs (like the
intestines or liver) to herniate into the thoracic cavity. The most common site for this defect is
the left posterolateral side (Bochdalek hernia).

• CDH can lead to pulmonary hypoplasia (underdevelopment of the lungs) because of the pressure
exerted by the herniated organs on the lungs during fetal development.

• Eventration of the Diaphragm:

• This is a condition where the diaphragm is abnormally elevated due to incomplete muscular
development, often resulting from improper fusion of the diaphragm’s components. It can cause
respiratory issues and is typically diagnosed via imaging studies.

• Diaphragmatic Agenesis:

• This is a rare but severe condition where there is a complete absence of the diaphragm. It
usually leads to death shortly after birth due to severe respiratory failure.

• Situs Inversus:

• Although not directly related to diaphragm formation, situs inversus (a condition where internal
organs are reversed in their position) can sometimes be associated with diaphragm development
anomalies.

• Congenital Hiatal Hernia:

 • This occurs when part of the stomach protrudes into the thoracic cavity through the diaphragm’s
esophageal hiatus. It is often diagnosed later in life and can cause symptoms like acid reflux or
difficulty swallowing.

• Clinical Implications and Diagnosis

• Anomalies in the development of body cavities and the diaphragm can lead to severe clinical
conditions, such as respiratory distress, digestive issues, and compromised organ function. These
conditions are often diagnosed prenatally through imaging techniques like ultrasound or MRI.
Treatment usually involves surgery, and early intervention is crucial for survival, particularly in
cases of congenital diaphragmatic hernia.

• Understanding the embryological development of these structures, as described in Langman’s

Medical Embryology, helps in recognizing the basis of such anomalies and their potential
impacts on the newborn's health.

• Surfactant production, crucial for lung expansion after birth, starts around week 24 of pregnancy
but increases dramatically in the final weeks of gestation.

• Vascularization is key to the development of the respiratory system, as blood vessels need to
surround the developing alveoli for gas exchange.

This developmental sequence highlights how the respiratory system forms from a simple outgrowth of
the foregut to a complex, functional organ capable of supporting breathing after birth. The process
involves intricate changes in the airway structure, lung tissue, and vascular system.

Development of the Heart:

1. Early Development (Week 3):

o The heart develops from mesodermal cells and begins to form in the third week of
embryogenesis.

o Initially, the heart is a simple tube formed by the fusion of two endocardial heart tubes
derived from the lateral mesoderm.

o These tubes fuse at the midline to form the primitive heart tube.

2. Formation of the Heart Tube (End of Week 3):

o The heart tube elongates and undergoes a series of folding processes. The heart tube
consists of the following regions:

▪ Sinus venosus: Receives blood from the body.

▪ Primitive atrium: Precursor to the atria.

▪ Primitive ventricle: Precursor to the ventricles.

 ▪ Bulbus cordis: Precursor to parts of the right ventricle and outflow tract.

▪ Truncus arteriosus: Becomes the aorta and pulmonary trunk.

3. Folding of the Heart Tube (Week 4):

o The heart tube folds in a looping process to establish a more definitive shape, aligning
the primitive chambers in a way that mimics the adult heart structure (atrium above,
ventricle below).

o The looping of the heart tube brings about the formation of the atrioventricular canal,
which will eventually form the atrial and ventricular septa.

4. Formation of Septa (Week 5–8):

o Septation of the Atrium: The atrial septum forms from two main structures:

▪ The septum primum (initial partition) grows toward the endocardial cushions.

▪ The septum secundum develops to the right of the septum primum, and the
two septa form an opening called the foramen ovale, which allows blood to flow
between the right and left atria in the fetal heart.

o Ventricular Septation: The ventricular septum begins to form between the left and right
ventricles, starting at the endocardial cushions and extending upwards.

o Outflow Tract Septation: The truncus arteriosus and bulbus cordis undergo further
division to separate the aorta from the pulmonary trunk, completing the division of the
outflow tract into two separate vessels.

5. Maturation of the Heart (Weeks 8–12):

o The heart undergoes further maturation, including the formation of the valves, coronary
arteries, and other important structures necessary for postnatal circulation.

Common Cardiac Anomalies:

1. Atrial Septal Defect (ASD):

o An abnormal opening between the left and right atria, usually caused by failure of the
septum primum or septum secundum to fuse properly. This allows oxygenated blood to
flow from the left atrium into the right atrium.

2. Ventricular Septal Defect (VSD):

o A hole in the interventricular septum that allows oxygen-rich blood from the left
ventricle to mix with oxygen-poor blood in the right ventricle. This condition can vary in
size and severity.

3. Patent Ductus Arteriosus (PDA):

 o The ductus arteriosus, which connects the pulmonary trunk to the aorta in fetal
circulation, fails to close after birth, resulting in a left-to-right shunt of blood.

4. Tetralogy of Fallot:

o A complex congenital defect involving:

▪ Ventricular septal defect (VSD)

▪ Pulmonary stenosis (narrowing of the pulmonary valve)

▪ Overriding aorta (aorta is positioned directly over the VSD)

▪ Right ventricular hypertrophy (thickening of the right ventricle due to the

increased workload)

5. Transposition of the Great Arteries (TGA):

o The aorta and pulmonary trunk are switched, leading to a situation where oxygen-poor
blood is circulated through the body, and oxygen-rich blood circulates through the lungs.

6. Coarctation of the Aorta:

o A narrowing of the aorta, usually occurring near the ductus arteriosus. This can result in
increased blood pressure in the upper body and decreased blood flow to the lower
body.

7. Hypoplastic Left Heart Syndrome (HLHS):

o A condition where the left side of the heart, including the left ventricle, mitral valve, and
aorta, is underdeveloped. This severe anomaly often requires surgical intervention early
in life.

8. Ebstein's Anomaly:

o A malformation of the tricuspid valve, where the valve is displaced downward into the
right ventricle. This results in a poorly functioning valve and an enlarged right atrium.

These cardiac anomalies often arise from disruptions in the normal process of heart formation,
particularly during the complex stages of septation, looping, and outflow tract division.

In summary, the development of the heart involves a series of critical steps, and errors during any of
these stages can lead to congenital heart defects. Early and accurate diagnosis of these anomalies is
crucialDevelopment of the Arterial System:

1. Embryonic Vascular Development:

o The arterial system develops primarily from three sources: the aortic arches, the
vitelline arteries, and the umbilical arteries.

o The aortic arches form the major arterial pathways of the head, neck, and thorax. These
arches arise from the truncus arteriosus of the heart and pass through the pharyngeal
arches.
 2. Aortic Arches (I-VI):

o First Arch: Contributes to the maxillary artery (small contribution).

o Second Arch: Contributes to the stapedial artery.

o Third Arch: Forms the common carotid artery and the proximal part of the internal
carotid artery.

o Fourth Arch: On the left, forms the part of the aortic arch; on the right, forms the
subclavian artery.

o Fifth Arch: This arch usually regresses and does not contribute significantly to adult
vessels.

o Sixth Arch: Forms the pulmonary arteries, with the left side contributing to the ductus
arteriosus (a fetal shunt connecting the pulmonary artery to the aorta).

3. Transformation of the Aortic Arches:

o As the embryo develops, some parts of the arches regress, while others become
permanent vessels, such as the common carotid and subclavian arteries.

o The ductus arteriosus plays a crucial role in bypassing the lungs in fetal circulation and
later closes after birth.

4. Vitelline Arteries:

o These arteries arise from the yolk sac and supply the gastrointestinal tract. As
development progresses, they give rise to major vessels such as the celiac trunk,
superior mesenteric artery, and inferior mesenteric artery.

5. Umbilical Arteries:

o The umbilical arteries carry deoxygenated blood from the fetus to the placenta. After
birth, the umbilical arteries close and become the medial umbilical ligaments.

6. Cardinal Veins:

o The cardinal veins develop alongside the arteries and eventually form the venous return
system, including the superior and inferior vena cavae.

Arterial System Anomalies:

1. Persistent Ductus Arteriosus:

o The ductus arteriosus fails to close after birth, leading to abnormal blood flow between
the pulmonary artery and the aorta. This condition can cause left-to-right shunting and
increased pulmonary circulation.

2. Double Aortic Arch:

 o A rare anomaly where both the right and left aortic arches persist, forming a ring around
the trachea and esophagus. This can cause respiratory or swallowing difficulties.

3. Right Aortic Arch:

o This occurs when the right aortic arch persists instead of the left. It can result in aberrant
branching patterns and is often associated with congenital heart defects.

4. Coarctation of the Aorta:

o A narrowing of the aorta that can occur at various locations, often near the ductus
arteriosus. This causes increased blood pressure in the upper body and reduced blood
flow to the lower body.

5. Aberrant Subclavian Artery:

o In this anomaly, the subclavian artery arises from the right aortic arch and passes behind
the esophagus, potentially compressing it and leading to dysphagia (difficulty
swallowing).

6. Congenital Absence of the Internal Carotid Artery:

o The internal carotid artery may fail to develop properly, which can lead to a lack of blood
supply to parts of the brain. This can be compensated for by the external carotid artery
in some cases.