Lung and Diaphragm Development

Duke LEARNING RESOURCES EB3: Lung and Diaphragm

Click here to launch the Simbryo Lung Development animation (and some really trippy music -you'll understand once the window opens...)

I. Development of the Respiratory Tract

A. Early development

Disruption of the mesoderm, retinoic acid signaling, or TBX4 expression in the endoderm will interfere with this process and can cause defects in lung/trachea development.

Disruption of the formation of the tracheo-esophageal ridges can result in tracheo-esophageal fistulas. This is very often associated with a spectrum of mesodermal defects called the VATER association (Vertebral anomalies, Anal atresia, Tracheoesophageal fistula, Esophageal atresia, and Renal atresia), or, if Cardiac defects and Limb defects are also present, VACTERL.

Tracheoesophageal fistulas occur in about 1/3000 births and most are of the sort where the proximal esophagus ends blindly whereas the distal esophagus communicates with the trachea via a fistula. Complications arise both prenatally and postnatally:

An extreme example is tracheal atresia where the trachea fails to form entirely and the lungs bud directly from the esophagus.

B. Development of the larynx

The process of recanalization can be disrupted resulting in laryngeal atresia (occlusion of the laryngeal lumen, also known as CHAOS, or Congenital High Airway Obstruction Syndrome) or laryngeal web (partial occlusion via a membranous web over the vocal cords). Either of these can be repaired surgically. However, the effects of laryngeal atresia are much more severe: air is trapped in the lungs causing dilation of the lower airways.

C. Development of the trachea

D. Segmental branching and development of the bronchial tree

Branching morphogenesis is MESODERM and RETINOIC ACID-DEPENDENT (along with several other genetic factors such as TBX4 and FGF10, for example). Early disruption of segmental branching can cause the loss, or agenesis, of entire bronchopulmonary segments, lobes, or even an entire lung. Congenital lung cysts arise if the disruption is later in development such that the terminal bronchioles within a small portion of the lung are abnormally dilated. These dilated pockets appear as empty "cysts" in a chest x-ray.

E. Development of the lungs

Because of the fewer number of mature alveoli, the lungs of a newborn are much denser than those of an adult when viewed on a chest x-ray.

F. Surfactant production

Surfactant Protein A plays a role in eliciting uterine contractions by activating as a pro-inflammatory agent on macrophages present in the amniotic fluid. These activated macrophages invade the uterine wall and begin releasing Interleukin-1, which ultimately leads to localized prostaglandin production that stimulates the uterine smooth muscle to contract.

II. Growth of lungs into the body cavity and development of the diaphragm

A. Separation of the pleural and pericardial cavities

B. Separation of the abdominal and thoracic cavities

Closure of the pericardioperitoneal canals is a complex process and disruptions are a frequent cause of congenital diaphragmatic hernias (CDH), in which abdominal contents herniate or protrude into the pleural cavity. The most common site of herniation is at the aortic or esophageal hiatus, but the overall effects are minor since the size of the defect is small. CDH rarely occurs on the right side since the liver is in the way. However, failure of the pericardioperitoneal canal to close on the left can lead to a large defect allowing the intestines to herniate into the left pleural cavity and interfere with development of the left lung, in some cases causing complete agenesis of the left lung.

Questions 1 and 2 refer to the following case: A 35 year-old woman delivers an infant at 40 weeks of gestation (based on the last time of menstruation). While in the neonatal care unit, the infant develops cyanosis and very rapid labored breathing and requires admission to the neonatal intensive care unit. Imaging studies of the thoracic cavity show congestion in the lungs but they appear to be of normal size and there is no apparent abnormality in the diaphragm. The woman reports no family history of lung disease and denies alcohol use, smoking, or taking medications during her pregnancy, and review of the mothers medical records regarding prenatal care and ultrasound imaging is unremarkable.

1. A biopsy of the infant's lung tissue would most likely show:

ANSWER

2.A possible cause of the infant's condition is:

ANSWER

3. The period of lung development in which NO respiratory bronchioles or alveoli have yet formed is known as the:

ANSWER

4. The period of lung development in which surfactant production begins (but is not necessarily sufficient to prevent airway collapse) is known as the:

ANSWER

5. The skeletal muscle of the diaphragm is derived primarily from:

ANSWER

6. The smooth muscle in the wall of the respiratory tract is derived from:

ANSWER

7. Congenital diaphragmatic hernias:

ANSWER

For items 8 10 , select the one lettered option from the following list that is most closely associated with each numbered item below. Options in the list may be used once, more than once, or not at all. a. alveolar stage b. canalicular stage c. terminal sac stage d. pseudoglandular stage 8. stage in lung development at which alveoli have not formed and survival is NOT possible ANSWER

9. premature infants born at this stage have a relatively good prognosis although they will require respiratory support and treatment with exogenous surfactant ANSWER

10. stage in lung development at which there is the most surfactant production ANSWER

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Updated 10/11/11 - Velkey

Read more here:
Duke Embryology - Lung and Diaphragm