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Embryology and Histology of the Lungs
- 1. Embryology and Histology of the Lungs Edited by: Std,Dr. Orlando Joseph Course: General Pathology School: Georgetown American University
- 2. EMBRYOLOGY OF THE LUNGS
- 3. Overview of Lung Development
- 4. Respiratory Primordium The respiratory system starts as a median outgrowth, the laryngotracheal groove, which appears in the floor of the caudal end of the anterior foregut (primordial pharynx) This primordium of the tracheobronchial tree develops caudal to the fourth pair of pharyngeal pouches. The endodermal lining of the laryngotracheal groove forms the pulmonary epithelium and glands of the larynx, trachea, and bronchi. The connective tissue, cartilage, and smooth muscle in these structures develop from splanchnic mesoderm surrounding the foregut By the end of the fourth week, the laryngotracheal groove has evaginated (protruded) to form a pouch-like laryngotracheal diverticulum (lung bud), which is located ventral to the caudal part of the foregut
- 5. As this diverticulum elongates, it is invested with splanchnic mesenchyme. Its distal end enlarges to form a globular respiratory bud that denotes the single bud from which the respiratory tree originates The laryngotracheal diverticulum soon separates from the primordial pharynx; however, it maintains communication with it through the primordial laryngeal inlet Longitudinal tracheoesophageal folds develop in the diverticulum, approach each other, and fuse to form a partition, the tracheoesophageal septum, at the end of the fifth week
- 6. This septum divides the cranial portion of the foregut into a ventral part, the laryngotracheal tube (the primordium of the larynx, trachea, bronchi, and lungs), and a dorsal part (the primordium of the oropharynx and esophagus The opening of the laryngotracheal tube into the pharynx becomes the primordial laryngeal inlet The separation of the single foregut tube into the trachea and esophagus results from a complex and coordinated process of multiple signaling pathways and transcription factors
- 7. Trachea Development During its separation from the foregut, the laryngotracheal diverticulum forms the trachea and two lateral outpouchings, the primary bronchial buds The endodermal lining of the laryngotracheal tube distal to the larynx differentiates into the epithelium and glands of the trachea and the pulmonary epithelium. The cartilage, connective tissue, and muscles of the trachea are derived from the splanchnic mesenchyme surrounding the laryngotracheal tube
- 8. Lung & Bronchi Development A respiratory bud (lung bud) develops at the caudal end of the laryngotracheal diverticulum during the fourth week . The bud soon divides into two outpouchings, the primary bronchial buds. These buds grow laterally into the pericardioperitoneal canals, the primordia of the pleural cavities .Secondary and tertiary bronchial buds soon develop. Together with the surrounding splanchnic mesenchyme, the bronchial buds differentiate into bronchi and their ramifications in the lungs. Early in the fifth week, the connection of each bronchial bud with the trachea enlarges to form the primordia of the main bronchi The embryonic right main bronchus is slightly larger than the left one and is oriented more vertically.
- 9. The main bronchi subdivide into secondary bronchi that form lobar, segmental, and intrasegmental branches. On the right, the superior lobar bronchus will supply the upper (superior) lobe of the lung, whereas the inferior bronchus subdivides into two bronchi, one to the middle lobe of the right lung and the other to the lower (inferior) lobe. On the left, the two secondary bronchi supply the upper and lower lobes of the lung. Each lobar bronchus undergoes progressive branching. The segmental bronchi, 10 in the right lung and 8 or 9 in the left lung, begin to form by the seventh week. As this occurs, the surrounding mesenchyme also divides. The segmental bronchi, with the surrounding mass of mesenchyme, form the primordia of the bronchopulmonary segments
- 10. By 24 weeks, approximately 17 orders of branches have formed and respiratory bronchioles have developed. An additional seven orders of airways develop after birth. As the bronchi develop, cartilaginous plates develop from the surrounding splanchnic mesenchyme. Mesenchyme develops the bronchial smooth muscle and connective tissue and the pulmonary connective tissue and capillaries. As the lungs develop, they acquire a layer of visceral pleura from the splanchnic mesenchyme. With expansion, the lungs and pleural cavities grow caudally into the mesenchyme of the body wall and soon lie close to the heart. The thoracic body wall becomes lined by a layer of parietal pleura derived from the somatic mesoderm .The space between the parietal and visceral pleura is the pleural cavity.
- 11. MATURATION PHASES OF THE LUNGS
- 12. Pseudoglandular Stage (5 to 17 Weeks) Pseudoglandualr stage looks like exocrine glands as the lungs develop. By 16 weeks, all major elements of the lung have formed, except those involved with gas exchange Hence, respiratory ducts have already been formed, The primordial system of passages, the air- conducting bronchial tree, is initially coated by cubic epithelium. These are the precursor cells of the ciliated epithelium and of the secretory cells. In the respiratory part the first typically lung- specific cells, connected to the terminal bronchioli, appear:the type II pneumocytes (alveolar cells) The developing broncho-pulmonary epithelium begins to produce amniotic fluid, which is also found in the lungs up to the time of birth
- 13. Canalicular Stage (16 to 25 Weeks) The canalicular stage overlaps the pseudoglandular stage because cranial segments of the lungs mature faster than caudal ones. During the canalicular stage, the lumina of bronchi and terminal bronchioles become larger and the lung tissue becomes highly vascular By 24 weeks, each terminal bronchiole has formed two or more respiratory bronchioles, each of which divides into three to six passages, the primordial alveolar ducts. Respiration is possible at the end of the canalicular stage (26 weeks) because some thin-walled terminal sacs (primordial alveoli) have developed at the ends of the respiratory bronchioles and lung tissue is well vascularized. Although a fetus born toward the end of this period may survive if given intensive care, this premature neonate may die because its respiratory and other systems are still relatively immature.
- 14. Saccular Stage (24 Weeks to Late Fetal Period) During the saccular stage, many more terminal sacs (primordial alveoli) develop and their epithelium becomes very thin. Capillaries begin to bulge into these sacs. The intimate contact between epithelial and endothelial cells establishes a blood–air barrier, which permits adequate gas exchange for survival of the fetus if it is born prematurely. At 26 weeks type I pneumoctyes lines the sacs to aloe for gas exchange. The capillary network proliferates rapidly in the mesenchyme around the developing alveoli and lymphatic capillaries. Type II pneumocytes develops and secrete pulmonary surfactant, a complex mixture of phospholipids and proteins.
- 15. Surfactant forms(begins at 20 to 22 weeks) 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 terminal sacs by preventing atelectasis (collapse of sacs during exhalation). The maturation of type II pneumocytes and surfactant production varies widely in fetuses of different gestational ages. The production of surfactant increases during the terminal stages of pregnancy, particularly during the last 2 weeks. By 26 to 28 weeks, the fetus usually weighs approximately 1000 g and sufficient alveolar sacs and surfactant are present to permit survival of a prematurely born infant
- 16. Alveolar Stage (Late Fetal Period to 8 Years) The epithelial lining of the sacs attenuates to a thin squamous epithelial layer. The type I pneumocytes become so thin that the adjacent capillaries bulge into the alveolar sacs(32wks). By the late fetal period (38 weeks), the lungs are capable of respiration because the alveolocapillary membrane (pulmonary diffusion barrier or respiratory membrane) is sufficiently thin to allow gas exchange. At the beginning of the alveolar stage (32 weeks), each respiratory bronchiole terminates in a cluster of thin-walled alveolar sacs, separated from one another by loose connective tissue. These sacs represent future alveolar ducts 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 organs into organs capable of gas exchange Establishment of parallel pulmonary and systemic circulations
- 17. Approximately 95% of mature alveoli develop postnatally. Alveolar development is largely completed by 3 years of age, but new alveoli are added until approximately 8 years of age. Lung development during the first few months after birth is characterized by an exponential increase in the surface area of the air–blood barrier through the multiplication of alveoli and capillaries. Fetal breathing movements (FBMs), which can be detected by real-time ultrasonography, occur before birth, exerting sufficient force to cause aspiration of some amniotic fluid into the lungs. FBMs occur intermittently (approximately 30% of them during rapid eye movement sleep) and are essential for normal lung development The fluid in the lungs at birth (half filled) is cleared at birth by three routes: Through the mouth and nose by pressure on the fetal thorax during vaginal delivery Into the pulmonary capillaries, arteries, and veins Into the lymphatics
- 18. HISTOLOGY OF THE LUNGS
- 19. Fetal Lungs
- 20. Early Lung Development and Maturation Pseudoglandular Phase Canalicular Phase
- 21. Saccular Phase
- 22. Alveolar Phase
- 23. Adult Lungs Section of Respiratory system Respiratory Epithelium Trachea Lungs Bronchus Bronchioles Alveoli Cells of Alveoli Blood air barrier Histological study of the Lungs H&E stain Elastin stain Reticular fiber stain Silver stain Trichrome Stain Movat's Pentachrome Stain Electron Microscopy (TEM)- (SEM)
- 26. Trachea
- 27. Respiratory Epithelium of Trachea
- 30. The Lungs Tissue
- 34. Bronchus
- 36. Bronchus Lining
- 39. The Alveolus
- 41. A.Capillary Alveolar space A.Septum A.C (Type I) A.C (Type II) RBC’sA.M E.C
- 42. Cells of the Alveoli
- 45. Capillaries of Alveoli H&E A.Capillaries SEM(EM) A.Capillaries LM(Normarski optics)-Plastic section(uranyl acetate and lead citrate)
- 49. Reticular Fibers of the Lungs
- 50. Elastic Fiber of Lung
- 52. References Moore.L.Keith PHD.Persuad.T.V.N.PHD.Torschia.G.Mark PHD.Developing Human.10th Edition. Elsevier Inc. Chapter 10.Respiratory system .Embryology of the lungs.page195-207 Douglas.F.Paulsen(PHD).Histology and cell biology examination and boards review.5th edition.Mc.Graw Hill.Respiratory system Southern Illinois University School of Medicine.Respiratory.retrived .Histology of the respiratory system from http://www.siumed.edu/~dking2/crr/rsguide.htm Dr. med. H. Jastrow.Electron micrscpoic atlas of cells,tiisues and organs in the internet.Respiratory.Retrived from https://www.uni- mainz.de/FB/Medizin/Anatomie/workshop/EM/externes/Wartenberg/Leber3.jpg
Editor's Notes
- Right Bronchi-This relationship persists in the adult; consequently, a foreign body is more likely to enter the right main bronchus than the left one.
- Respiration is not possible in this phase; therefore fetuses born during this period are unable to survive. More info Relatively early in the development of the lungs, endocrine-active cells (Kultschitsky cells) appear that produce bombesin and serotonin. In contrast to the precursors of the pneumocytes, which originate from the endoderm, they stem from the neural crest (neuroectoderm). Via paracrine mechanisms bombesin probably plays a decisive role for lung development in that mainly the type II pneumocytes proliferate.
- surfactant is present in only small amounts in premature infants; it does not reach adequate levels until the late fetal period. . Before 26-28weeks, the lungs are usually incapable of providing adequate gas exchange, partly because the alveolar surface area is insufficient and the vascularity underdeveloped. Fetuses born at 24 to 26 weeks after fertilization may survive if given intensive care; however, they may suffer from respiratory distress because of surfactant deficiency. Survival of these infants has improved with the use of antenatal corticosteroids (steroids produced by the adrenal cortex), which induces surfactant production, and also with postnatal surfactant replacement therapy.
- Although the lungs do not begin to perform this vital function until birth, they are well developed so that they are capable of functioning as soon as the baby is born.
- Three factors are important for normal lung development: adequate thoracic space for lung growth, FBMs, and adequate amniotic fluid volume
- Pseudostriated ciliated columnar epithelium
- Apical portion of ciliated epithelium. Arrows (from left to right) indicate: central, peripheral microtubules of axoneme and plasma membrane. Microvilli (Mv) are also present. Inset is cilia in cross section: Each axoneme contains nine peripheral pairs and two central pairs of microtubules.
- In the trachea you should be able to identify the following structures: respiratory epithelium, basement membrane, submucosal glands (both serous and mucous parts), perichondrium, tracheal cartilage and trachealis muscle (smooth muscle). One can perceive different appearances of the connective tissue immediately below the epithelium and the connective tissue surrounding the submucosal glands, but the elastic lamina forming the border between the mucosa and submucosa is not visible in H&E stained slides. Accumulations of very dark small dots represent lymphocytes (not illustrated). If present, you are likely to see them close to the glandular tissue.
- This image shows the pseudostratified columnar epithelium that lines the mucosa of the trachea. This epithelium consists of both short and tall cells, all resting on the basement membrane
- The lining of the respiratory tract from the trachea to the larger diameter bronchioles is pseudostratfied epithelium. There are three main cell types in this epithelium: ciliated cells that reach the lumen; goblet cells with mucinogen granules which also reach the lumen; and basal cells which are confined to the basal portion of the epithelium (and act as progenitors for the other types).
- In this specimen of lung, the prominent dark-reddish structures are blood vessels filled with blood. (Histological preparation often washes away blood, rendering blood vessels much less conspicuous.) Also, this lung is not fully inflated so alveolar walls appear somewhat wrinkled.
- Respiratory (terminal) bronchioles are lined by simple cuboidal epithelium and open into respiratory ducts or alveoli. Note the small artery (art) accompanying the bronchiole. A network of capillaries is included in each alveolar wall.
- Most of this image is occupied by the air spaces of alveoli (the smallest sacs) and respiratory ducts (channels among interconnected alveoli). Bronchi and bronchioles are generally associated with blood vessels which follow the same branching tree structure. Note the arteries, including the smaller artery to the left of the one labelled, and also the arteriole which may be seen passing below the bronchiole at lower right. Keep in mind that the thin walls separating alveoli include a network of capillaries. Airway walls are supported by connective tissue. Bronchial walls also including cartilage, with larger tubes having more cartilage.
- bronchus: find one with noted features, VE: p. 247, at 100x: alveoli bronchus or bronchiole: significance or characteristics: mucosal folds pseudostratified ciliated columnar epithelium lamina propria connective tissue underlying mucous membrane smooth muscle forms a smooth pink ring outside mucosa adventitia often filled with lymphoid tissue lymph node nuclei numerous, stained blue-purple pulmonary artery thick walled pulmonary vein thin walled, collapsed, if present Here is a labeled view of a bronchus.
- The low columnar epithelium of this bronchiole contrasts with the simple squamous endothelium of the adjacent arteriole. The round nuclei forming a row in each wall of the arteriole are those of smooth muscle fibers, cut in cross section as they wrap around the longitudinally-sectioned vessel.
- This image shows ciliated, pseudostratified columnar epithelium lining a bronchus, with a gland and smooth muscle in the bronchial wall.
- This specimen illustrates a portion of a bronchiole adjacent to several alveoli. Bronchioles typically have simple cuboidal epithelium, in contrast to the pseudostratified columnar epithelium of larger bronchi and the trachea. Different types of bronchiolar cells (ciliated and secretory) cannot be readily distinguished in this image. Blood has been retained in blood vessels, so the conspicuous presence of red blood cells serves to reveal the location of alveolar capillaries.
- Terminal bronchiole showing ciliated cells (ci) and Clara cells (C). Lumen (L), smooth muscle, cut in cross section (SM)
- The interstitium at (1) is tissue between two layers of alveolar epithelial cells containing elastic and collagen fibers produced by fibroblasts (also known as septal cells). There is no connective tissue over the capillaries
- Alveolus and capillaries E.C-endothelial cell A.C-alveolar cell
- This image shows the alveolar walls separating adjacent air sacs (the large empty areas in the image). Each alveolar wall has a simple squamous epithelium lining each exposed surface, with a thin stroma of capillaries and delicate supporting connective tissue sandwiched in between. These details cannot be clearly resolved in this image. Flat nuclei in the alveolar wall represent either Type I pneumocytes (squamous cells) or capillary endothelium. Round nuclei may represent Type II pneumocytes (surfactant-secreting great alveolar cells). Monocytes from circulating blood can crawl out of the alveolar capillaries, cross the alveolar epithelium, and enter the alveolar air space. These alveolar macrophages, or dust cells, can then crawl over the free surface and scavenge dust particles and bacteria that have been inhaled. Ingested material can accumulate in lysosomal vesicles and become visible as lipofuscin granules. Eventually, these macrophages may re-enter the blood or ascend the airways where ciliary action carries them up the trachea until they are swallowed with mucus.
- Type II pneumocyte protruding into alveolar lumen. Arrows indicate lamellar bodies containing the phospholipids that when released spread over the alveolar surface where they combine with other carbohydrate- and protein-containing secretory products (some of which are derived from Clara cells) to overcome the effects of surface tension which would otherwise cause the alveolar walls to adhere. This allows for normal inflation of the alveoli at birth and for the reinflation of alveoli which collapse after airway obstruction. Rough endoplasmic reticulum (RER), Golgi (G), reticular fibers (RF). Note the microvilli of the type II cell and junctional complexes (JC) with type I cell.
- 1 Picture is H& E stain of alveoli capillary 2 Picture is SEM of Alveoli capillaries
- This micrograph illustrates one capillary within an alveolar wall. Includes portions of several glomerular capillaries. Gas molecules diffusing from alveolar air space to capillary lumen (or vice versa) must pass through the alveolar epithelium and the capillary endothelium as well as the intervening basement membranes.
- Transmission electron micrographs of cross sections of a human alveolus showing at lower magnification on the left, a section through an alveolar capillary containing four red blood cells (RBCs). At higher magnification on the right the air–blood barrier can be seen to be composed of two cells, the alveolar epithelial cell and the capillary endothelial cell. Both cell types are attached to an extracellular basement membrane (interstitium). The dominant permeability barrier is thought to be the epithelial cell and not the basement membrane or the endothelial cell. Photographs by E. R. Wiebel, reprinted with permission
- Very high-power electron micrograph showing the pulmonary blood-gas barrier. Note that the extracellular matrix contains a band of electron-dense material which is believed to be the type IV collagen. A, alveolar space; C, capillary; EP, epithelium; EN, endothelium; PM, plasma membrane; BM, basement membrane; EC, erythrocyte. Calibration bar is 0.2 μm. [Borrowed with permission from
- Reticular and elastic fibres form the bulk of the connective tissue present in the walls of the alveoli. You have seen both types of fibres previously. Note that if you mentally superimpose the elastin and reticulin stains there is not much space for anything other than capillaries. Collagenous fibres are sparse and fine in the alveolar walls. Note also that the tissue stained for reticular fibres looks much denser than the other sections. This lung collapsed prior to fixation because of the recoil of the elastic fibres. Because of this artifact it may be a little easier to recognize alveolar ducts than in the other sections.
- Low magnification of Elastic fibers of the Lungs
- At higher magnification, HA22 shows the large number of elastic fibers in the walls of the alveoli (a), and a bronchiole (b)