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09-24-10-Respiratory-Embryology-Hrubec-Outline by huanghengdong


									09-24-10 Embryology of the Respiratory System (Hrubec) – Outline

     Weeks 3-4
                          rd    th
           o Over the 3 to 4 week:
                    Gastrulation completes.
                    The embryo folds.
                    The neural tube forms and closes.
                    Somites form, mesoderm begins to differentiate.
                    The heart and cardiovascular system begin to function.
                    Pharyngeal arches form.
                               Pharyngeal arches are derived from neural crest tissue and will go on to
                                  become structures of the face, nose, mouth, larynx, pharynx and neck.
                                      o Each pharyngeal arch is composed of the following:
                                                 An artery connecting the ventral primordial heart with the
                                                     dorsal aorta.
                                                 A cartilaginous rod supporting each arch.
                                                 A musclular core.
                                                 Sensory and motor nerves that supply the mucosa and
                                                     muscles of the arch.
                                      o In the 4 week, neural crest tissue migrates the arches forming the
                                           bulk of each arch.
                                      o The epiglottis originates from cartilage of both the third and forth
                                      o the cartilages of the larynx are derived from the fourth and sixth arch.
                                      o The intrinsic muscles of the larynx are formed by the sixth arch.
New Material
     Laryngotracheal Tube
           o The lower respiratory tract begins to form in the 4 week shortly after the embryo folds.
           o An outpouching, the laryngotracheal groove, forms on the ventral surface of the foregut at the
              level of the 6 pharyngeal arch  deepens to form the laryngotracheal diverticulum, a sac like
              structure coming off the foregut in the throat region of the early embryo.
           o The laryngotracheal divirticulum grows out into mesoderm tissue that will later form the
                    Since the laryngotracheal diverticulum originates off the foregut, it is lined with
                        endoderm and covered with visceral (splanchnic) mesoderm.
                               The endoderm lining will form the respiratory epithelia and glandular
                                  structures in the larynx, trachea and bronchi.
                               The outer mesoderm layer will form the smooth muscle and cartilage of the
                                  trachea and bronchial system.
           o As the diverticulum elongates, folds called tracheoesophageal folds, form on each side of the
              diverticulum as it comes off the foregut.
                    The tracheoesophageal folds grow inward and fuse to form the tracheoesophageal
                        septum which separating the elongating laryngotracheal diverticulum from the
           o Communication with the pharynx is maintained through an opening, the primordial laryngeal
     Larynx
                                                                                 th   th
           o The cartilages of the larynx develop from mesenchyme of the 4 and 6 pharyngeal arch.
                    This mesenchyme proliferates at the proximal end of the laryngotracheal tube forming
                        arytenoid swellings.
                               These paired swellings will become the arytenoid and other laryngeal
                  The epiglottis forms from mesenchyme originating in the 4 pharyngeal arch. The
                      mesenchyme migrates to the hypopharyngeal eminence and forms an epiglottal
                            The epiglottal swelling elongates into the epiglottis.
                  The laryngeal epithelium proliferates closing off the lumen of the larynx and the
                      laryngeal inlet until the 10 week of gestation.
                            During this time, the vocal folds and vestibular folds form within the larynx.
                  At 10 weeks the lumen of the larynx and trachea reopens (recanalizes).
                                                                                    th      th
        o    The laryngeal muscles develop from myoblasts originating within the 4 and 6 pharyngeal arch.
                                                 th    th
                  Because of their origin (4 and 6 arch), the laryngeal musculature is innervated by CN
                      X, the vagus nerve.
        o    Growth of the larynx and epiglottis continues for approximately three years after birth.
   Trachea
        o The laryngotracheal tube elongates distal to the forming larynx.
                 The endoderm lining of the developing trachea differentiates into epithelial and
                      glandular cells.
                 The outer splanchnic mesoderm forms the cartilage rings and muscles of the trachea.
        o Incomplete separation of the trachea from the esophagus (by the tracheoesophageal septum)
            results in a tracheoesophageal atresia and fistula formation.
                 This is the most common malformation of the lower respiratory tract occurring in
                      ~1/4000 births.
   Bronchi
        o An enlargement, the respiratory bud, appears on the distal laryngotracheal diverticulum in the
            4 week shortly after the diverticulum forms.
                 The respiratory bud consists of a blind ended tubular space, lined with endoderm, and
                      covered by an outer mesoderm layer.
                 The space within the respiratory bud is connected to the foregut through
                      laryngotracheal tube and the primordial laryngeal inlet.
                 The tube within the respiratory bud elongates and branches numerous times to form
                      the bronchial tree
        o The respiratory bud divides first into right and left primary bronchial buds (lung buds).
                 By the 5 week, the primary bronchial buds have further divided into secondary and
                      then tertiary bronchial buds.
                            These initial divisions set up the basic lobular structure of the lungs (three lobes
                               on the right and two on the left)
                 The bronchial buds continue to divide forming the segmental bronchi thus establishing
                      the bronchopulmonary segments of the adult. and the bronchioles.
                 Further divisions form the bronchioles, and finer branches of the bronchial tree. By 24
                      weeks, 17 orders of branches have developed.
        o Branching of the bronchial tree continues after birth as the lungs continue to enlarge.
   Lungs
        o As the bronchial tree is developing, the parenchyma of the lung is developing as well.
                 The developing lungs grow, expanding into the pleural cavity. The outer layer of
                      mesenchyme becomes the visceral pleura.
                 The mesoderm also differentiates into a loose fibrous connective tissue with smooth
                      muscle cells and vascular capillary network.
                 As the lungs mature and expand, the amount of space occupied by the endoderm lined
                      bronchial tree increases, leaving relatively less mesoderm derived interstitial tissue.
        o There are four stages of lung maturation:
                 Pseudoglandular – 6-16 weeks
                         6-16 weeks of age
                         Terminal bronchioles are lined with simple columnar epithelium.
                         Developing lungs resemble exocrine glands histologically.
                         Gas exchange elements have not formed.
                         Respiration is not possible.
                         Premature infants born in this stage can not survive.
                 Canalicular – 16-26 weeks
                         16-26 weeks
                         Terminal bronchioles enlarge and branch into respiratory bronchioles.
                         Respiratory bronchioles branch into primordial alveolar ducts.
                         The respiratory epithelium is now composed of simple cuboidal cells.
                         A prominent capillary network forms.
                         A fetus born toward the end of this period has a chance for survive but
                              requires intensive care.
                                   o Infants born before 20 weeks rarely survive.
                 Terminal Sac – 26 weeks to birth
                         26 weeks to birth
                         Alveolar ducts branch off terminal sacs (primordial alveoli).
                         Some epithelial cells thin to allow for gas exchange forming type I
                              pneumocytes. Type II pneumocytes, which secrete surfactant, proliferate.
                         Capillaries and lymphatics proliferate.
                         Surfactant is present at 20 weeks but in low amounts.
                         Surfactant production becomes sufficient for respiration at 26-28 weeks; but
                              production is not at full capacity until two weeks before birth.
                         Vascular development and surfactant production are both critical for survival.
                         Preterm infants born at this time can survive with intensive care
                 Alveolar – 32 weeks to 8 years
                         32 weeks to 8 years
                         Terminal sacs become thinner and capillaries extend into the lumen of the
                         Before birth, the fetus begins fetal breathing movements to help develop
                              respiratory musculature and lungs.
                         At birth, the fluid in the lungs is forced out the nose and mouth during vaginal
                              delivery, and also is resorbed rapidly by the lymphatics and vasculature.
                         Alveoli expand with the first breath, filling with air.
                         A full term infant has 150 million alveoli. The majority of the remaining alveoli
                              (300 million in adults) form in the first 6 months after birth.
                         Respiratory bronchioles and primordial alveoli continue to form and develop
                              into mature alveoli until 8 years of age.
        o   Lung maturation is not uniform throughout the lung. Tissue closest to the hilum matures first
            and may be at a later stage of maturation than more distant tissue
   Pathology – Congential Defects
        o Incomplete separation of the trachea from the esophagus (by the tracheoesophageal septum)
            results in tracheoesophageal atresia and / or tracheoesophageal fistula formation.
                  This is the most common malformation of the lower respiratory tract and occurs in
                      ~1/4000 births.
        o Respiratory Distress Syndrome
                  seen in 2% of live births
                  caused by insufficient surfactant production
                            Terminal sacs and alveoli are unable to open.
                          This condition affects primarily premature infants but can also affect full term infants.
                           It causing rapid labored breathing.
             o Pulmonary Agenesis:
                      Absence of a lung or lobe caused by failure of the bronchial buds to develop.
             o Pulmonary Aplasia:
                      Absence of lung tissue but with a rudimentary bronchial tree caused by a failure in
                           mesoderm development.
             o Pulmonary Hypoplasia:
                      Poorly developed bronchial tree and lung tissue. Can be caused by:
                                 Insufficient amniotic fluid (Oligohydramnios) results in lung hypoplasia by
                                    restricting fetal breathing movements in late gestation.
                                 Congenital diaphragmatic hernia when a loop of intestine develops within the
                                    pleural cavity preventing normal development of the lung
Additional Images (end of lecture)

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