Respiratory System Department of human anatomy and histology University of Babylon . College of medicine Dr. Haythem Ali Alsayigh

Respiratory system The respiratory system is an outgrowth of the ventral wall of the foregut, and the epithelium of the larynx, trachea, bronchi, and alveoli originates in the endoderm. The cartilaginous, muscular, and connective tissue components arise in the mesoderm. In the fourth week of development, the tracheoesophageal septum separates the trachea from the foregut, dividing the foregut into the lung bud anteriorly and the esophagus posteriorly. Contact between the two is maintained through the larynx, which is formed by tissue of the fourth and sixth pharyngeal arches.

The lung bud develops into two main bronchi: the right forms three secondary bronchi and three lobes; the left forms two secondary bronchi and two lobes. Faulty partitioning of the foregut by the tracheoesophageal septum causes esophageal atresias and tracheoesophageal fistulas

After a pseudoglandular (5-16 weeks) and canalicular (16-26 weeks) phase, cells of the cuboidal-lined bronchioles change into thin, flat cells, type I alveolar epithelial cells, intimately associated with blood and lymph capillaries

In the seventh month, gas exchange between the blood and air in the primitive alveoli is possible. Before birth, the lungs are filled with fluid with little protein, some mucus, and surfactant, which is produced by type II alveolar epithelial cells and which forms a phospholipid coat on the alveolar membranes

At the beginning of respiration, the lung fluid is resorbed except for the surfactant coat, which prevents the collapse of the alveoli during expiration by reducing the surface tension at the air-blood capillary interface. Absent or insufficient surfactant in the premature baby causes respiratory distress syndrome (RDS) because of collapse of the primitive alveoli (hyaline membrane disease).

Growth of the lungs after birth is primarily due to an increase in the number of respiratory bronchioles and alveoli and not to an increase in the size of the alveoli. New alveoli are formed during the first 10 years of postnatal life. Surfactant :Phospholipid made by alveolar type II cells that reduce surface tension in alveoli, which is essential for respiration. Production does not begin until the end of the sixth month, making it difficult for premature infants born before this time to survive.

Formation Of The Lung Buds When the embryo is approximately 4 weeks old, the respiratory diverticulum (lung bud) appears as an outgrowth from the ventral wall of the foregut

Introduction Formation Of The Lung Buds The appearance and location of the lung bud are dependent upon an increase in retinoic acid (RA) produced by adjacent mesoderm This increase in RA causes upregulation of the transcription factor TBX4 expressed in the endoderm of the gut tube at the site of the respiratory diverticulum. TBX4 induces formation of the bud and the continued growth and differentiation of the lungs

Formation Of The Lung Buds Hence, epithelium of the internal lining of the larynx, trachea, and bronchi, as well as that of the lungs, is entirely of endodermal origin. The cartilaginous,muscular, and connective tissue components of the trachea and lungs are derived from splanchnic mesoderm surrounding the foregut.

Formation Of The Lung Buds the lung bud is in open communication with the foregut When the diverticulum expands caudally, however, two longitudinal ridges, the tracheoesophageal ridges, separate it from the foregut . Subsequently, when these ridges fuse to form the tracheoesophageal septum, the foregut is divided into a dorsal portion, the esophagus, and a ventral portion, the trachea and lung buds The respiratory primordium maintains its communication with the pharynx through the laryngeal orifice

Lateral View of partitioning of the foregut into esophagus and respiratory diverticulum

Respiratory diverticulum Sections showing the formation of the tracheoesophageal septum separating the foregut into trachea and lung bud (anteriorly) and esophagus(post). Respiratory diverticulum

Clinical Correlations Abnormalities in partitioning of the esophagus and trachea by the tracheoesophageal septum result in esophageal atresia with or without tracheoesophageal fistulas (TEFs). These defects occur in approximately 1/3,000 births, and 90% result in the upper portion of the esophagus ending in a blind pouch and the lower segment forming a fistula with the trachea Isolated esophageal atresia and H-type TEF without esophageal atresia each account for 4% of these defects. Other variations each account for approximately 1% of these defects. These abnormalities are associated with other birth defects, including cardiac abnormalities, which occur in 33% of these cases.

Clinical Correlations In this regard, TEFs are a component of the VACTERL association 1-Vertebral anomalies, 2-Anal atresia, 3-Cardiac defects, 4-Tracheoesophageal fistula, 5- Esophageal atresia, 6- Renal anomalies, and Limb defects), a collection of defects of unknown causation, but occurring more frequently than predicted by chance alone.

Larynx The internal lining of the larynx originates from endoderm, but the cartilages and muscles originate from mesenchyme of the fourth and sixth pharyngeal arches. As a result of rapid proliferation of this mesenchyme, the laryngeal orifice changes in appearance from a sagittal slit to a T-shaped opening.

Subsequently, when mesenchyme of the two arches transforms into the thyroid, cricoid, and arytenoid cartilages, the characteristic adult shape of the laryngeal orifice can be recognized

Larynx, developmental Stages Its epithelial lining is endodermal. 4th & 6th Pharyngeal arches mesenchyme gives rise to the larynx cartilages and muscles. Laryngeal inlet changes from slit like opening to T-shaped inlet.

LARYNX Sup Laryngeal N = 4th Recurrent Laryngeal N = 6th Rapid proliferation of the epithelia of the larynx will result in temporary occlusion of the lumen, then vacuolization and recanalization produce 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 Since the muscles of the larynx derived from the 4th &6th pharyngeal arches, so all laryngeal mus supplied by branches of the vagus: Sup Laryngeal N = 4th Recurrent Laryngeal N = 6th

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 fifth week, each of these buds enlarges to form right and left main bronchi The right then forms three secondary bronchi, and the left, two thus foreshadowing the three lobes on the right side and two on the left With subsequent growth in caudal and lateral directions, the lung buds expand into the body cavity

Trachea, Bronchi & Lungs During separation from the foregut; the lung bud Trachea Bronchial buds Trachea

Trachea, Bronchi & Lungs At the beginning of the 5th week: each bronchial bud enlarge Rt main bronchus Lt main bronchus U L U L M Secondary bronchi Secondary bronchi

Trachea, Bronchi & Lungs The spaces for the lungs, the pericardioperitoneal canals, are narrow. They lie on each side of the foregut and are gradually filled by the expanding lung buds. Ultimately 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

Trachea, Bronchi & Lungs Further development; the secondary bronchi will divided repeatedly forming 10 tertiary (segmental) on the Rt 8 tertiary (segmental) on the Lt creating the bronchopulmonary segments of the adult lung

By the end of the sixth month, approximately 17 generations of subdivisions have formed. Before the bronchial tree reaches its final shape, however, an additional six divisions form during postnatal life

Branching is regulated by epithelial-mesenchymal interactions between the endoderm of the lung buds and splanchnic mesoderm that surrounds them. Signals for branching, which emit from the mesoderm, involve members of the fibroblast growth factor family. While all of these new subdivisions are occurring and the bronchial tree is developing, the lungs assume a more caudal position, so that by the time of birth, the bifurcation of the trachea is opposite the fourth thoracic vertebra.

Trachea, Bronchi & Lungs Caudal & lateral expansion of the lung buds into the pericardioperitoneal canal Ultimately formation of the 2 folds: Pleuroperitoneal fold Pleuropericardial fold the remaining is the pleural cavity The mesoderm which covers the lung is the visceral pleura The mesoderm which line the thoracic wall is the parietal pleura

Trachea, Bronchi & Lungs By the end of the 6th month >17 generation of subdivisions formed Postnatal; additional 6 divisions formed Branching is regulated by ep – mesenchymal interaction. At time of birth the biforcation of the trachea = T4 vertebra

Maturation of the Lungs Pseudoglandular period 5-16 wk Branching has continued to form terminal bronchioles. No respiratory bronchioles or alveoli are present . Canalicular period 16-26 wk Each terminal bronchiole divides into 2 or more respiratory bronchioles, which in turn divide into 3-6 alveolar ducts

Maturation of the Lungs Terminal sac period 26 wk to birth Terminal sacs (primitive alveoli) form, and capillaries establish close contact Alveolar period 8 mo to childhood Mature alveoli have well-developed epithelial endothelial (capillary) contacts.

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 present 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 I 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 the end of the sixth month. These cells, type II alveolar epithelial cells, produce surfactant, a phospholipid-rich fluid capable of lowering surface tension at the air-alveolar interface.develops at

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

As concentrations of surfactant increase during the 34th week of gestation, some of this phospholipid enters the amniotic fluid and acts on macrophages in the amniotic cavity. Once “activated,” evidence suggests that these macrophages migrate across the chorion into the uterus where they begin to produce immune system proteins, including interleukin-1β (IL-1β

Upregulation of these proteins results in increased production of prostaglandins that cause uterine contractions. Thus, there may be signals from the fetus that participate in initiating labor and 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 phospholipid coat on alveolar cell membranes. With air entering alveoli during the first breath, the surfactant coat prevents 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

Clinical Correlates Surfactant is particularly important for survival of the premature infant. When surfactant is insufficient, the air-water (blood) surface membrane tension becomes high, bringing great risk that alveoli will collapse during expiration. As a result, respiratory distress syndrome (RDS) develops

This is a common cause of death in the premature infant This is a common cause of death in the premature infant. In these cases, the partially collapsed alveoli contain a fluid with a high protein content, many hyaline membranes, and lamellar bodies, probably derived from the surfactant layer

RDS, which is therefore also known as hyaline membrane disease, accounts for approximately 20% of deaths among newborns. Recent development of artificial surfactant and treatment of premature babies with glucocorticoids to stimulate surfactant production have reduced the mortality associated with RDS and allowed survival of some babies as young as 5.5 months of gestation

many abnormalities of the lung and bronchial tree have been described (e.g., blind-ending trachea with absence of lungs and agenesis of one lung), most of these gross abnormalities are rare. Abnormal divisions of the bronchial tree are more common; some result in supernumerary lobules. These variations of the bronchial tree have little functional significance,

but they may cause unexpected difficulties during bronchoscopies. More interesting are ectopic lung lobes arising from the trachea or esophagus. It is believed that these lobes are formed from additional respiratory buds of the foregut that develop independently of the main respiratory system.

Most important clinically are congenital cysts of the lung, which are formed by dilation of terminal or larger bronchi. These cysts may be small and multiple, giving the lung a honeycomb appearance on radiograph, or they may be restricted to one or more larger ones. Cystic structures of the lung usually drain poorly and frequently cause chronic infections

Maturation of the Lungs 1. Pseudoglandular period a. Lungs major elements are formed, except its gas exchange tissue. b. Respiration is not possible c. Fetuses born at this period will not survive.

2.Canalicular period a. Bronchi and terminal bronchioles lumens enlarge b. Vascularization of Lung tissue c. Formation of respiratory bronchioles. d. Increase of alveolar ducts. e. Respiration is possible at the end of this period f. Terminal saccules,( primordial alveoli) are formed. g. fetus born at the end of this period dies.

3. Terminal Saccular Period a.Saccules develop with thin epithelium b. Capillaries bulge into the lumen of the alveoli. c. Blood air barrier permits adequate gas exchange. d. Terminal saccules are lined by squamous epithelial cells, type I alveolar cells or pneumocytes, which permit gas exchange. e. fetus born at this stage will survive. f. Capillary network proliferates. g. Type II alveolar cells(developed at the end of the 6th month of gestation) or pneumocytes secrete pulmonary surfactant

*Surfactant forms as a monomolecular film over the internal walls of the terminal saccules, to lower surface tension at the air alveolar interface. h. Production of surfactant increases during the terminal stages of pregnancy. Surface tension is a property of the surface of a liquid that allows it to resist an external force

H. Pulmonary Surfactant 1 H. Pulmonary Surfactant 1. Surfactant counteracts surface tension and facilitates expansion of the terminal saccules (primordial alveoli).. 2.Surfactant deficiency cause respiratory distress. 3. Surfactant is adequate in the late fetal period. 4.Before this, the lungs are a. incapable of providing adequate gas exchange, b. insufficient alveolar surface area c. underdeveloped vascularity 5. Adequate pulmonary vasculature and sufficient surfactant are critical to survival.

4. Alveolar Period a. Terminal sacs epithelium become squamous. b. Type I alveolar cells become thin and capillaries bulge into the terminal saccules. c. Late fetal period, the lungs are capable of respiration. 5. Replacing placental gas exchange to lung gas exchange requires the following lung changes . a. Adequate surfactant in the alveoli b. Lung changes from secretory to gas exchange c. Presence of parallel pulmonary and systemic circulation

Saccules: Primordial Alveoli Alveolocapillary membrane is thin . Capillaries bulging into terminal saccules

SUMMARY 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 of the purely conductive respiratory tract.

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

The Lungs After Birth 1. Maturation of 95% of alveoli. 2 The Lungs After Birth 1. Maturation of 95% of alveoli . 2. Respiratory bronchioles and primordial alveoli, increase in number. 3. About 1/6th of the adult No. of alveoli, are present in the lungs of a full term newborn baby And during the first 10 yrs the other 5/6th develop 4. Lung radiographs, of newborn infants are denser than adult lungs.

Breathing movements 1.Occur before birth. 2.Done by exerting force to cause aspiration of amniotic fluid into the lungs. 3.Fetal breathing movements. (ultrasonography) 4. Are essential for normal lung development. 5. At birth the lungs fluid, derived from the a. Amniotic cavity, b. Lungs, c. Tracheal glands.

Lungs of a Newborn 1. Healthy lungs contain some fluid; 2 Lungs of a Newborn 1. Healthy lungs contain some fluid; 2. Pulmonary tissue will float in water . 3. Diseased lung, may not float. 4. Medico legal fact:Lungs of a stillborn infant (born dead), are firm and sink in water because they contain fluid, not air.

Respiratory Distress Syndrome (RDS) 1 Respiratory Distress Syndrome (RDS) 1. Also known as hyaline membrane disease (HMD). 2.Surfactant deficiency is a major cause of RDS. 3. Lungs are under inflated 4. Alveoli contain fluid with high protein content. 5. Administration of exogenous surfactant (surfactant replacement therapy) reduces the severity of RDS and neonatal mortality

Congenital Lung Cysts 1.Cysts (filled with fluid or air) 2. If several cysts are present, the lungs have a honeycomb appearance on radiographs. Agenesis of Lungs Failure of bronchial buds development. Lung Hypoplasia In congenital diaphragmatic hernia (CDH), interfere with the lung development due to the pressure of abnormally positioned abdominal viscera. Lung hypoplasia is, reduced lung volume.

the end thank you

(Breathing): Lungs unnecessary for IU existence. Should be ready to function following birth.

Introduction they are important source of amniotic fluid During intrauterine life . 15 ml/kg BW produced.