Reminders: Tomorrow 3/21 is the last day to withdraw from this class Exam 2 will be given on 4/3/14 (the

he Thursday after your Spring Break) and will be composed of questions from both Dr. Schmidt and Dr. McGinley The final exam is scheduled for Monday, May 5 from 10:30 am - 12:30 pm. Location TBA

The drug cyclopamine is produced by California corn lily. Pregnant animals grazing on the plant have cyclopic offspring like this lamb.

Cyclopic infant born in 2006. Survived 1 day after birth.

Most cases of cyclopia are fatal due to breathing problems (nonfunctional nose/mouth) or brain defects.

Cyclopamine is currently in clinical trials as an anti-cancer drug (Saredigib / IPI-926).

Development of the Respiratory System

Learning Objectives Name the parts of the adult respiratory system and their function. Which parts conduct air and which parts do gas exchange? Identify the germ layer origins of the respiratory system. Describe how the developing lungs separate from the foregut. Explain how blood is oxygenated within the alveoli of the lungs. Describe what tissues are formed during each of the 5 stages of lung development. Understand the role of surfactant in lung function. What are the consequences of having insufficient surfactant at birth? Describe the cause, symptoms and treatments for the following congenital lung disorders: tracheoesophageal fistula, infant respiratory distress syndrome, alveolar capillary dysplasia, and pulmonary hypoplasia.

Trachea (windpipe) connects the pharynx/larynx to the lungs Lining is endoderm and the cartilage is mesoderm

Primary bronchi/lung buds Secondary bronchi

Conductive airways

Tertiary bronchi

Primary bronchioles
Terminal bronchioles Respiratory bronchioles Alveolar ducts Alveolar sacs Alveoli

Respiratory airways

The functional tissues of the respiratory system are made of endoderm. Tissues that surround the functional tissues (i.e. cartilage, muscle, connective tissues) are derived from splanchnic mesoderm.

Laryngotracheal groove (respiratory diverticulum) precursor of the lungs and trachea. It is a ventral evagination from the esophageal endoderm of the foregut.

Fusion of the tracheoesophageal septum (ridge) causes separation of the trachea and esophagus.
The diverticulum elongates and branches forming lung buds. The straight portion will form the trachea. The lung buds will give rise to the mature lung.

At around 4 weeks, lung (bronchial) buds form at the caudal end of the respiratory diverticulum

The lung buds become the primary bronchi Right primary bronchi = right lung; left primary bronchi = left lung
Secondary (lobar) bronchi grow out from the primary bronchi Three on the right and two on the left Will eventually give rise to the lobes of the lung Tertiary bronchi grow from the secondary bronchi

Primary bronchioles grow out from the tertiary bronchi Terminal bronchioles grow out from the primary bronchioles Respiratory bronchioles grow from the terminal bronchioles Alveolar ducts branch from the respiratory bronchioles and give rise alveolar sacs Alveolar sacs eventually give rise to alveoli

Gas exchange takes place between the alveoli capillaries and the alveoli The respiratory membrane (diffusion path length) is two cell layers thick Each alveoli is very small, but the combined surface area for gas exchange is 70 square meters (about the size of a badminton court)

Structure of the respiratory system between weeks 4 and 7:

5 stages of lung development

Stage 1 Embryonic stage (4-7 weeks) Formation of the respiratory diverticulum through formation of tertiary bronchi

Stage 2 Pseudoglandular stage (816 weeks) Formation of the rest of the conductive airway Stops after formation of the terminal bronchioles

Stage 3 Canalicular stage (17-26 weeks) Formation of respiratory bronchioles and alveolar ducts from the terminal bronchioles Blood vessels begin to grow into the lungs, and capillaries become associated with the respiratory bronchioles Stage 4 Terminal/saccular/alveolar stage (26 weeks birth) Alveoli (terminal air sacs) bud from the alveolar ducts Type I alveolar cells gas exchange Type II alveolar cells production of pulmonary surfactant

Stage 5 Postnatal stage (birth approximately 8 years old) Mature lungs contain about 300 million alveoli, about 90% of which are formed after birth This is due to the formation of secondary septa that divide the alveoli

1. 2. 3. 4. 5. 6.

Alveolar duct Primary septum Alveolar sac Type I pneumocyte Type II pneumocyte Capillaries

1. 2. 3. 4. 5. 6.

Alveolar duct Secondary septum Alveolar sac Type I pneumocyte Type II pneumocyte Capillaries

http://www.embryology.ch/anglais/rrespiratory/phasen06.html

http://www.embryology.ch/anglais/rrespiratory/phasen01.html

Lungs are not needed for respiration in utero, but are necessary immediately upon birth Before birth, the fetus lungs are filled with liquid Liquid is usually composed of surfactant and amniotic fluid Upon birth, the fluid needs to be quickly removed and replaced with oxygen Fluid is removed by the lungs in three ways: 1. Pressure on the fetus chest as it moves through the birth canal 2. Entrance into the pulmonary circulation via the alveolar capillaries 3. Entrance into the lymphatic system via the bronchioles An infant takes a first breath as a reflex, and this breath causes all of the respiratory passageways to open Hydrostatic test used to determine if a fetus was alive at the time of birth The theory: if the fetus was alive at the time of birth, it would have taken a breath, the lungs would fill with air, and they would therefore float when placed in water If the fetus was stillborn at the time of birth, it would not take a breath, the lungs would not inflate and would sink when placed into water

Malformations of the Lungs Tracheoesophageal fistula (TEF) an Abnormal connection between the trachea and the esophagus, usually due to a failure of the tracheoesophageal ridges to fuse. Co-occurs with esophageal atresia (EA) Symptoms = problems feeding and abdominal distention Treatment = surgical repair

Malformations of the Lungs, continued Infant Respiratory Distress Syndrome Formerly called hyaline membrane disease because of lung histology Symptoms = difficulty breathing, cyanosis Associated with premature infants, gestational diabetes. Due to lack of surfactant. 1% of all births. Leading cause of death for premature infants. Treatments = artificial surfactant, oxygen via breathing machines. Corticosteroids given before birth can speed lung maturation. Alveolar capillary dysplasia Capillaries fail to properly form around the alveoli Shortly after birth, infants experience respiratory distress Usually results in death of the newborn In July 2012, the first newborn with ACD was kept alive via use of an artificial lung followed by a lung transplant

Malformations of the Lungs, continued Pulmonary hypoplasia Underdevelopment of the lungs Found frequently in premature infants. Can be caused by diaphragm hernias, cysts/tumors , dextrocardia, hydrops fetalis. Symptoms = Reduced lung volume leads to respiratory distress, often death Treatment = oxygenation, surgical repair of causal disorder, corticosteroids.