EMBRYOLOGI OF THE RESPIRATORY SYSTEM

Arti Rosaria Dewi, dr

Embryonic disc begins to fold endoderm lined cavity primitive gut - the anterior end: fore gut, - the posterior end: hind gut - mid gut connected to yolk-sac The opening between fore gut and mid gut : anterior intestinal portal Between hind gut and mid gut : posterior intestinal portal

Primitive gut or tubular gut mouth, pharynx, digestive tube

Fore gut specializes into: mouth, pharynx, part of digestive tube Hind gut rest of small, intestine, colon, rectum

Mid gut will: disappear

Derivatives of the endodermal digestive tube: - respiratory system - thyroid, parathyroid, thymus - liver, vesica felea and pancreas

The epithelial lining of digestive and respiratory tracts : endoderm

Accessory coats : muscle and connective tissue from splanchnic mesoderm tunica mucosa

THE NOSE

Ventrolateral of the head thickened olfactory placodeolfactory pit. Peripheral of the pit median and lateral nasal processnasal septum.

- Maxillary and nasal processnostril - Olfactory epitheliumolfactory nerve

Formation of the Lung Buds

+ 4 weeks old the embryo :

the respiratory diverticulum (laryngotrakheal diverticulum) - An outgrowth from the ventral wall of the foregut. - The location is determined by signals from the surrounding mesenchyme, including fibroblast growth factors (FGFs) that instructs the endoderm.

Epithelium of the internal lining of the larynx, trachea, bronchi, and the lungs, endodermal origin. The cartilaginous, muscular, and connective tissue components of the trachea and lungs splanchnic mesoderm

Initially the lung bud is in open communication with the foregut. When the diverticulum expands caudally : the tracheoesophageal ridges
the tracheoesophageal septum the foregut is divided into : - a dorsal portion, the esophagus, - a ventral portion, the trachea and lung buds.

Abnormalities in partitioning of the esophagus and trachea

Result in esophageal atresia +/tracheoesophageal fistula (TEFs). 1/3000 births 90 % result in the upper portion of the esophagus ending in a blind pouch and the lower segment forming a fistula with the trachea (A).

Isolated esophageal atresia (B): 4 % H-type TEF without esophageal atresia : 4 %. Other variations (D & E) : 1 %. Associated with other birth defects, cardiac abnormalities : 33 %.

TEFs are a component of the VACTERL (Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects). Complication TEFs : - polyhydramnion - Pneumonitis

The respiratory primordium maintains its communication with the pharynx through the laryngeal orifice.

LARYNX

The internal lining of the larynx : endoderm. The cartilages & muscles : mesenchyme of the 4th & 6th pharyngeal arches. Rapid proliferation of this mesenchyme changes the laryngeal orifice ( a sagittal slit T-shaped opening)

mesenchyme of the two arches transforms into : - the thyroid - cricoid, and - arytenoids cartilages (the characteristics adult shape)

At about the time that the cartilages are formed, the laryngeal epithelium also proliferates rapidly a temporary occlusion of the lumen. Subsequently, vacuolization and recanalization a pair of lateral recesses, the laryngeal ventricles. These recesses are bounded by folds of tissue that differentiate into the false and true vocal cords.

All laryngeal muscles are innervated by branches of the 10th cranial nerve, the vagus nerve. - The superior laryngeal : derivatives of the 4th pharyngeal arch, and -The recurrent laryngeal : derivatives of the 6th pharyngeal arch.

Trachea, Bronchi, and Lungs

During its separation from the foregut, the lung bud forms : - the trachea and - two lateral outpocketings, the bronchial buds. At the beginning of the 5th week, each of these buds enlarges to form right and left main bronchi.

The right forms three secondary bronchi the three lobes, and The left forms two secondary bronchi the two lobes.

Lung buds lie on each side of the foregut and are gradually filled the pericardioperitoneal by the expanding lung buds.

The pleuroperitoneal and pleuropericardial folds separate the pericardioperitoneal canals from the peritoneal and pericardial cavities, respectively, and the remaining spaces form the primitive pleural cavities.

The mesoderm, which covers the outside of the lung, develops into the visceral pleura. The somatic mesoderm layer, covering the body wall from the inside, becomes the parietal pleura. The space between the parietal and visceral pleura is the pleural cavity.

Secondary bronchi forming 10 tertiary (segmental) bronchi in the right lung and 8 in the left, creating the bronchopulmonary segments of the adult lung. The end of the sixth month 17 generations of subdivisions have formed. An additional 6 divisions form during postnatal life.

Branching is regulated by epithelialmesenchymal interactions ( the endoderm of the lung buds - splanchnic mesoderm that surrounds them). Signals for branching : members of the fibroblast growth factor (FGF) family. by the time of birth the bifurcation of the trachea is opposite the fourth thoracic vertebra.

Maturation of the Lungs

Up to the seventh prenatal month, the bronchioles divide continuously into more and smaller canals (canalicular phase), and the vascular supply increases steadily. Respiration becomes possible when some of the cells of the cuboidal respiratory bronchioles change into thin, flat cells.

These cells are intimately associated with numerous blood and lymph capillaries, and the surrounding spaces are now known as terminal sacs or primitive alveoli. During the seventh month, sufficient numbers of capillaries are presents to guarantee adequate gas exchange, and the premature infant is able to survive.

During the last 2 months of prenatal life and for several years thereafter, the number of terminal sacs increases steadily. In addition, cells lining the sacs.known as type 1 alveolar epithelial cells, become thinner,so that surrounding capillaries protrude into the alveolar sacs. This intimate contact between epithelial and endothelial cells makes up the blood-air barrier. Mature alveoli are not present before birth.

In addition to endothelial cells and flat alveolar epithelial cells, another cell type develops at the end of the sixth month. These cells, type II alveolar epithelial cells, produce surfactant, a phospolipid-rich fluid capable of lowering surface tension at the airalveolar interface.

Before birth the lungs are full of fluid that contains a high chloride concentration, little protein, some mucus from the bronchial glands, and surfactant from the alveolar epithelial cells (type II). The amount of surfactant in the fluid increases, particularly during the last 2 weeks before birth.

Fetal breathing movements begin before birth and cause aspiration of amniotic fluid. These movements are important for stimulating lung development and conditioning respiratory muscles. When respiration begins at birth, most of the lung fluid is rapidly resorbed by the blood and lymph capillaries, and a small amount is probably expelled via the trachea and bronchi during delivery.

When the fluid is resorbed from alveolar sacs, surfactant remains deposited as a thin phospholipids coat on alveolar cell membranes. With air entering alveoli during the first breath, the surfactant coat presents development of an air-water (blood) interface with high surface tension. Without the fatty surfactant layer, the alveoli would collapse during expiration (atelectasis).

Respiratory movements after birth bring air into the lungs, which expand and fill the pleural cavity. Although the alveoli increase somewhat in size, growth of the lungs after birth is due primarily to an increase in the number of respiratory bronchioles and alveoli. It is estimated that only one-sixth of the adult number of alveoli are present at birth. The remaining alveoli are formed during the first 10 years of postnatal life through the continuous formation of new primitive alveoli.

Terminal Respiratory Unit (gas-exchange unit/acinus) - the basic functional unit of the lung. - consist : the structures distal to the terminal bronchiole - the respiratory bronchiale - alveolar ducts - alveoli

In the adult lung : - total gas volume 2500 ml - surface area 80 m2 Within the terminal respiratory units : 2 type intercommunicating channels provide collateral ventilation for the gas-exchanging units : 1. the alveolar pores of Kohn 2. the canals of Lambert

Add. 1 : - are holes in the alveolar wall of 3-13 um in diameter that provide channels for gas movement between contiguous alveoli. - are not present in newborn lungs.

Add.2 : - are accessory channels that connect a small airway to an air space normally supplied by a different airway.

Collateral Ventilation
In

the adult collateral ventilation the movement of gas from one acinus to another-occurs through holes in the alveoli, the pores of Kohn and epithelium-lined channels between terminal bronchioles & adjacent alveoli called the canals of Lambert.

These structures may be present in the infant lung, but they are probably not of sufficient size to allow for air drift. Although collateral pathway in the adult are probably not of great significance for ventilation they do prevent absorption of gas in regions distal to airway obstruction.

The relative absence of collateral pathway probably contribute to the patchy atelectasis so common in airway disease of infants & young children. The product of resistance & compliance the time constants, of these collateral pathways have been investigated in maturing sheep & in young adults.

The alveoli are lined by 2 types of epithelial cells: *the type I epithelial cell - extremely broad,thin cell(0.1-0.5 um) - covers 95% of the alveolar surface - is markedly differentiated cell possessing few organelles.
*the type II epithelial cell - more numerous than type I cell. - owing to their cuboidal shape. - occupy only 5 % of the alveolar surface area(table 3-1).

-characterized histologically by microvilli and osmophilic inclusion bodies. -the type II epithelial cell:maintains homeostasis within the alveolar space in several ways: 1.it is the source of pulmonary surfactant and as such indicates maturity of the lung;it decreases the surface tension at the alveolar air-liquid interface. 2.it cell is likely the precursor of the alveolar type I cell and thus plays a key role in the repair process following lung injury

3.it is capable of actively transporting ions against an electrochemical gradientand likely is involved in both fetal lung liquid secretion and, post natally, the reabsorption of fluid from the air space following the development of alveolar pulmonary edema. Two pediatric disorders associated with the type II epithelial cell: 1.hyaline membrane disease:its lack of maturity and surfactant secretion 2.alveolar proteinosis:its excessive and disordered secretion of surfactant

The cell junctions between alveolar type I and II cells are very tight and restrict the movement of both macromolecules and small ions such as sodium and chloride. This tightness is an essential characteristic of the cells lining the alveolar space; its enables the active transport of ions. Tight junctions provide a margin of safety for patients susceptible to pulmonary edema:significant interstitial pulmonary edema can be present without alveolar flooding occurring, thus preserving gas exchange.

The time constants of pathways in the young lung & in the right middle lobe are longer than those in the older lung & in regions other than the right middle lobe suggesting that atelectasis of the right middle lobe so common with generalized airway diseases in infants & young children, may in part be related to comparatively little collateral ventilation & air drift into regions obstructed by secretion & cellular debris.

CASE 2

A premature infant developed rapid, shallow respiration shortly after birth. A diagnosis of respiratory distress syndrome (RDS) was made. 1. How do you think the infant might attempt to overcome his or her inadequate exchange of oxygen and carbondioxide/ 2. what usually causes RDS? 3. what treatment is currently used clinically to prevent rds? 4. a deficiency of what substance is associated with RDS?

CASE 3

1. 2. 3.

The parents of a new born infant were told that their son had a fistula between his trachea and asophagus. What is the most common type of tracheosophageal fistula? What is its embryological basis? What anomaly of the digestive tract is frequently associated with this abnormality/

Case 4

1. 2.

A new born infant with esophageal atresia experienced respiratory distress with cyanosis shortly after birth. Radiographs demonstrated air in the infants stomach. How did the air enter the stomach? What other problem might result in an infant with this fairly common type of congenital anomaly?