The late maturation of the respiratory system with surfactant produced late in the third trimester, leads to the associated abnormality of Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease). A second group of abnormalities are associated not with directly with lung development, but with the supporting musculoskeletal structures in Congenital Diaphragmatic Hernia.
Introduction | Some Recent Findings | Tracheoesophageal Fistula | Lobar Emphysema (Overinflated Lung) | Newborn Respiratory Distress Syndrome (Hyaline Membrane Disease) | Congenital Diaphragmatic Hernia | Azygos Lobe | References | Glossary
Whitsett JA. Disorders of lung morphogenesis. Paediatr Respir Rev. 2006;7 Suppl 1:S248.
Colvin J, Bower C, Dickinson JE, Sokol J. Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia. Pediatrics. 2005 Sep;116(3):e356-63. (More? Congenital Diaphragmatic Hernia)
"For our study population, survival rates differed vastly depending on the subgroup analyzed. Ninety-two percent of postoperative infants survived beyond 1 year of age, as did 80% of infants who reached the surgical referral center. However, only 52% of live-born infants, 32% of all cases, and 16% of all prenatally diagnosed cases survived. Therefore, the overall mortality rate for this condition remains high, despite increased prenatal detection, transfer to tertiary institutions for delivery, and advances in neonatal care, and is influenced significantly by the rate of prenatal termination. In our study, 33% of all cases of CDH and 49% of prenatally diagnosed fetuses underwent elective termination of pregnancy. This large number of fetal terminations confounds the accurate assessment of the true outcomes of this condition."
Oesophageal Atresia with or without tracheo-oesophageal fistula
(Data: Congenital Malformations Australia 1981-1992 P. Lancaster and E. Pedisich ISSN 1321-8352)
Clinical Summary
Oesophageal atresia as suggested by
(a) Polyhydramnios
(b) Reflex increase in salivation
(c) Holdup of the catheter confirmed by the X-ray appearance of the dilated blind proximal oesophagus. The fistula is confirmed by the presence of gas in the intestines.
Management
1. Operative closure of the trachea end of the fistula.
2. Restoration of the continuity of the oesophagus
N.B. This is a serious malformation with significant risk of mortality
Associated Malformations
(a) Stratified squamous epithelium and columnar epithelia (mixtures of tracheal and oesophageal epithelial) are found in the trachea and oesophagus.
(b) This often occurs as one of a complex of malformations in a child. The origin is in early embryogenesis and often associated with
(i) cloacal malformation
(ii) cardiac septal defects
(iii) renal malformations
Questions
(a) The failure of what embryological process might give rise to this malformation?
(b) Why is there almost invariable association of tracheo oesophageal fistula with polyhydramnios?
(c) Why is there an early onset of pneumonia if the malformation is unrecognised?
(d) How might the defect possibly be corrected?
Embryology - Tracheoesophageal Septum
From the caudal end of the primitive pharynx a ventral outpocketing forms the laryngotracheal diverticulum.
Lateral longitudinal folds form and grow to fuse in the midline forming the tracheoesophageal septum.
Lengthwise fusion continues until the septum has completely formed.
Deviation of the septum posteriorly forms a tracheoesophageal fistula and esophageal atresia.
OMIM Database Entry Tracheosophageal Fistula
Search Now: Pubmed - Tracheoesophageal Fistula | OMIM - Tracheoesophageal Fistula
Links: American Academy of Family Physicians - Tracheosophageal Fistula
1. There is an overinflated left upper lobe
2. There is a collapsed lower lobe
3. The left lung is herniating across the mediastinum
Description of lesion - there is a congenital deficiency of cartilage in the left upper lobe bronchus. The anatomical nature of the lesion was demonstrated by autopsy specimens and usually reveals no abnormality other than cartilage deficiency throughout the lobe.
Summary
(a) Respiration is normal at first
(b) Once distress occurs overinflation is rapidly progressive and may kill by asphyxia.
(c) This is called Lobar Emphysema due to congenital broncho-malacia (soft bronchi).
Management
The affected lobe must be resected.
OMIM Database Entry Lobar Emphysema
Search Now: Pubmed - Lobar Emphysema | OMIM - Lobar Emphysema
Management
1. R.D.S. is normally treated conservatively with oxygen, intravenous bicarbonate and general supportive measures but the mortality rate is high in more premature infants. At autopsy the principle change to be seen is an eosinophilic hyaline membrane filling the alveoli.
2. If the child is treated with constant positive airway pressure this increases arterial 02 tension and helps prevent the collapse of alveoli which deficient surfactant otherwise causes. This increases the functional residual capacity of the lungs. This support system is effective in the nearly mature infants but the more premature still have a high mortality rate.
Search Now: Pubmed - Hyaline Membrane Disease | OMIM - Hyaline Membrane Disease
Failure of the pleuroperitoneal foramen (foramen of Bochdalek) to close allows viscera into thorax. Intestine, stomach or spleen can enter the pleural cavity, compressing the lung.
References:
Gallot D, Boda C, Ughetto S, Perthus I, Robert-Gnansia E, Francannet C, Laurichesse-Delmas H, Jani J, Coste K, Deprest J, Labbe A, Sapin V, Lemery D. Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study. Ultrasound Obstet Gynecol. 2007 Mar;29(3):276-83.
"501 cases of CDH were identified from a total of 1,835,022 live births (2.7/10 000 live births). The overall prenatal detection rate was 54%. The terminations of pregnancy (TOP) rate for isolated CDH did not vary significantly in contrast to that for associated CDH cases in which the TOP rate increased over time, progressively replacing the neonatal death rate (P = 0.01)."
Colvin J, Bower C, Dickinson JE, Sokol J. Outcomes of congenital diaphragmatic hernia: a population-based study in Western Australia. Pediatrics. 2005 Sep;116(3):e356-63.
"For our study population, survival rates differed vastly depending on the subgroup analyzed. Ninety-two percent of postoperative infants survived beyond 1 year of age, as did 80% of infants who reached the surgical referral center. However, only 52% of live-born infants, 32% of all cases, and 16% of all prenatally diagnosed cases survived. Therefore, the overall mortality rate for this condition remains high, despite increased prenatal detection, transfer to tertiary institutions for delivery, and advances in neonatal care, and is influenced significantly by the rate of prenatal termination. In our study, 33% of all cases of CDH and 49% of prenatally diagnosed fetuses underwent elective termination of pregnancy. This large number of fetal terminations confounds the accurate assessment of the true outcomes of this condition."
Search Now: Pubmed - Congenital Diaphragmatic Hernia | OMIM - Congenital Diaphragmatic Hernia
Common condition (0.5% of population). The right lung upper lobe expands either side of the posterior cardinal. There is also some course variability of the phrenic nerve in the presence of an azygos lobe.
Management
Condition is generally harmless.
Search Now: Pubmed - Azygos Lobe | OMIM - Azygos Lobe
Cardoso WV, Lu J. Regulation of early lung morphogenesis: questions, facts and controversies. Development. 2006 May;133(9):1611-24.
Yao Z, Liao W. Fungal respiratory disease. Curr Opin Pulm Med. 2006 May;12(3):222-7.
Parton LA, Strassberg SS, Qian D, Galvin-Parton PA, Cristea IA. The genetic basis for bronchopulmonary dysplasia. Front Biosci. 2006 May 1;11:1854-60.
You LR, Takamoto N, Yu CT, Tanaka T, Kodama T, Demayo FJ, Tsai SY, Tsai MJ. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16351-6.
Gallot D, Marceau G, Coste K, Hadden H, Robert-Gnansia E, Laurichesse H, Dechelotte PJ, Labbe A, Dastugue B, Lemery D, Sapin V. Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development? Birth Defects Res A Clin Mol Teratol. 2005 Aug;73(8):523-31.
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The respiratory system is an very interesting developing system at many different levels.
Firstly, in not carrying out its physiological function (gas exchange) prenatally. The lungs also continue to grow for about 8+ years postnatally.
Secondly, while the respiratory tract and aveolar epithelium are endoderm in origin (with mesoderm contributing surrounding tissue) many other tissues/systems are involved in respiratory function: musculoskeletal (ribs and diaphragm) cardiovascular (pulmonary circulation). The musculoskeletal begins functioning prenatally, the cardiovasular pulmonary circulation is activated and altered postnatally.
Thirdly, lung development goes through 4 stages, the final stage (type 2 surfactant secretion) only occurs in the final weeks of development. This means that premature infants have respiratory difficulties due to the still immature respiratory system. More recently, this has been treated in these infants with humidicribs and various surfactant therapies.
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