Fetal Lung Development

Bob Caruthers, csr, PLD

INTRODUCnON field. That scoring system remains in effect today, The presen- The 271hAnnual Congress of Anesthetists, a joint meeting of ter was Virginia Apgar, MD,'.' the International Anesthesia Research Society and the Apgar scores are assigned to all infants born in hospital set- International College of Anesthetists, was held in Virginia tings in the USA. Values of 9-2 are assigned to five categories: Beach, Va, on September 22-25, 1952. A member of the heart rate, respiratory effort, muscle tone, reflex irritability Department of Anesthesiology, Columbia University, College and color. The scores for each item are totaled for the Apgar of Physicians and Surgeons and the Anesthesia Service and score. The maximum score is 10. Higher scores are associated the Presbyterian Hospital presented a remarkable paper. The with greater health. Scores are assigned at one minute and article began: five minutes post partum. Scores continue to be assigned at five minutes intervals as long as the score is less than seven Resuscitation of infants at birth has been the subject of (See Table 1.)' many articles. Seldom have there been such imaginative The Apgar scoring system provides the clinician with a ideas, such enthusiasms, and dislikes, and such unscien- quick and easy tool for evaluation of the neonate. It provides tific observations and study about one clinical picture. insight into each of the key indicators of health: cardiac, res- There are outstanding exceptions to these statements, piratory, muscle tone, nervous system and oxygenation. This but the poor quality and lack of precise data of the article will focus on development related to one of these, majority of papers concerned with infant resuscitation namely lung development. are intere~ting.'.~ FETAL LUNG DEMLOPMMITu.7 The presenter, then, set forth the results of a careful scien- There are five stages to human lung development, which are tific study and established a grading system for clinical evalua- summarized in Table 2. An abbreviated but more detailed tion of the neonate that both revolutionized and stabilized the description follows.

TABLE; I.Apgar Scoring

m.cQIIU) tCQlllr1 : StO(Urt $;. " - Heart Rate Absent heart rate Heart rate < 100 :-H~tirate > 100

Respiratory Effort Absent Weak, irregular Qr gasping a Good effort, crying Muscle Tone Flaccid Some flexion of extremities Well flexed, or active move. men& of extremities Reflex Irritability No reflex responss Grimace or weak cry Good cry Color Blue all over or pale Acroqanosis (Raynaud's sign) )Pink all over i)'r At about three weeks gestational age, a ventral epithelial cells lining the alveolar airways. The splanchnic mesoderm evagination of the foregut forms the respiratory diverticulum. forms connective tissue, blood vessels and lymphatics in the The groove elongates caudally and is separated from the pulmonary alveoli. foregut by the tracheo-esophageal septum. At about four During the rapid lateral growth of the lung buds, the peri- weeks, a single lung bud forms at the end of the respiratory cardioperitoneal canals are progressively obliterated. These diverticulum. The lung bud-then divides into right and left canals are lined with mesothelium, the same type that lines primary bronchial buds. Branching occurs rapidly. Three main the pericardial and peritoneal cavities. As it develops, the branches form in the right lung bud and two in the left. These lung becomes coated with a visceral pleura that is reflected on initial branches correspond to the lobar bronchi of the tadu16 the parietal pleura at the mediastinum. lungs. The lung buds grow caudally and laterally, entering the The 17&to 28&weeks are noted for acinar development. pericardioperitoneal canals. The interaction between splanch- During this period, the portion of the lungs that will function nic mesoderm and the respiratory diverticulum is essential to for gas exchange is formed and vascularized. The initial respira- pulmonary development. tory bronchioles appear about the I?" week. The number of The respiratory diverticulum is of endodermal origin, and it connected capillaries continues to increase for some time. forms the epithelial lining of the respiratory system. The These capillaries connect to pulmonary instead of bronchi splanchnic mesodem is carried with the growing lung buds arteries. The saccules elongate with growth of the acini in- after they enter the pericardioperitoneal canals. Splanchnic ing the distance between terminal bronchioles and the pleura. mesoderm forms connective tissue, cartilage, smooth muscle Remarkable changes in lung appearance begin about the and blood vessels, all surrounding the epithelium. In the distal 28th week of gestation. There is a significant decrease in inter- development of the respiratory tract, the epithelium of the stitial tissue, and the airspace walls narrow and become more respiratory diverticulum forms the type I and type I1 epithelial compact. Lung volume and surface area increase rapidly. In

TABLE 2. Summary of Fetal Lung Development

mRWlt Embryonic Phase 4* - 6D week of gestation Initiation: Formation of laryngo- Structural abnormalities difficult tracheal groove to establish; developmental Termination: Formation of bron- errors at the point usually result chopulmonary segments in death Pseudoglandular Period 6D - 16" week of gestation All conducting airways formed Developmental errors result in by branching of the bronchial abnormalities of bronchial con- buds; Pleural membranes and .nection, position and number .. 'pitlmonary lymphatics develop %$ during weeks 8 10 +.' ,:;' - ,>-@ . Canalieular Period !-,knar development, the basic % &eiopmemal errors result in structure of the portion of the &,eficiencies~t of the components %lung responsible for gas $,.ofthe fung responsible for gas

* F.exchange is formed and ascw $hrjzed; airways lined by - cuboidal epithelium; parenchy- ma of lungs becomes highly -;vasculariad Saccular Period 3. Increase in lung volume and sur- elopmental errors result in .-face area; prenatal phase of cdeficiencies of the components ,'ialveolar development: squa- ?&f the lung responsible for gas mous type Icells develop: $exchange Surfactant-secretingtype II cells

develop .. v Alveolar Period 366 week of gestation to Surface area expansion contin- :Developmental errors result in 3 years post-term E; 50 million alveoli present deficiencies of the components birth and reaching 300 million a of the lung responsible for gas -, exchange - I" plasma until levels increase near term in response to the pres- ence of surfactant. Lung liquid is secreted at 4-6 cc/kg/hr. The lungs must be cleared of fluid in order to transition from the intrauterine to extrauterine environment. This process begins about three days prior to birth with a drop in secretion rate. The process begins in earnest with the onset of labor. Post partum liquid moves from the air spaces to loose connective tissue in the extra-alveolar interstitium as the lungs expand. Wacer is removed by lymphatic action and resorption into the vascular compartment.

DlAGNOSnC INDICATIONS Respiratory distress syndrome affects many neonates. Respiratory distress syndrome is related to premature birth and inadequate surfactant production. Normal signs of respi- ratory distress in the infant include flared nares and grunting during respiratory effort and cyanosis. Treatment for respira- tory distress syndrome, hyaline membrane disease, continues to develop.

The Apgar score is a clinician's tool. Other tests specifically FIGURE 1-Key steps of pulmonary development. focused on fetal lung maturity have been developed, and mod- em science has refined our understanding of the factors that humans, alveoli may appear by week 32 and are always present contribute to normal and pathologic conditions.z~'~'~5~6~~~BA by week 36. During the saccular stage, the great alveolar cells or surfactant-secreting type I1 cells are formed. Surfactant RLSOURCES 1. Apgar, V. A Proposal for a New Method of Evaluat~onof the Newborn forms a thin, continuous film of phospholipid and protein that Infant. Current Researches m Anesrhesln and Analgesln Jul-Aug. 1953.260. reduces surface tension at the interface of the fluid-filled alveo- (See also, Internet resources.) 2. Banks BA, Ischiropoulos H, McClelland M, Ballard PL, Ballard, RA. lus and the alveolar epithelium. The surfactant allows for easy Plasma 3-n1rrocyros1neIS elevated In premature lnfants who develop bron. inflation of the lungs. Once a sufficient amount of surfactant- chopulmonary dysplasta. Pedtamcs. 1998 May; 101 (5): 870-874. 3. Guyton, AC. Texrbook ofMe&cd Physiology. Bhed. Philadelph~a:WB secreting type I1 cells are formed, the fetus is viable outside the. Saunden Co; 1991. uterine environment. Prior to this time, the incidence of respi. 4. Johnson, KE. HmDevelopmenral Anacomy. Nm'd Medical Smes for Independent Scudy. Malvern, PA: Hanval Pub. Co; 1988. ratory distress syndrome is greatly increased. Surfactant secre- 5. McCarrhy K, Bhogal M, Nardi M, Hart D. Pathogen~cfactors m bron. tion can be used clinically to evaluate fetal lung maturity. chopulmonary dyspias~a.Pek Research. 1984 May; 18 (5): 483-488. 6, Ramsay PL, O'Brlan Sm~thE, Hegctm~rrS, Welty SE. Early cl~nicalmark- ers for the development of bronchopulmonary dysplas~a:soluble E. WNG LIQUID Select~nand ICAM-1, Pedtamcs 1998 Oft: 102 (4 Ptl): 927-932. The airways are open to contact with amniotic fluid when the INTERNET RESOURCES glottis is open. The lungs, buccal cavities and nasopharynx con- 7. [email protected] (Webmaster). Pulmonary Function in drc Newborn, Contribution from Division of Neonatology, Cedars-Sinai Medical tribute to the tracheal effluent. Except in instances of fetal dis- Center, Los Angeles, CA. www.neonatology.org/syllabus/pulmonary.html. tress, however, amniotic fluid rarely enters the lung proper. The 8. Tulane Medical School. Fetal Lung Maturity Testing. www.mcl .tukne.ed&kssware/pthology/medicalqathoIogy/pren...~FIM.hml. lungs are filled with fluid, but it differs from both amniotic fluid 9. Apgar, V. A Proposal for a New Method of Evaluation of the Newborn and plasma. Lung liquid is high in chloride with small amounts Infant. Current Researches in Anrsrhesia and Analgesia. July-Aug, 1953, 260. Available on-line at Neonatology on the Web. of bicarbonate and little protein. Potassium levels are similar to www.neonarol~.org/clnrsics/apgar.html.

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