• Reminders:

• Tomorrow 3/21 is the last day to withdraw from this class

• Exam 2 will be given on 4/3/14 (the 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

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.

The drug cyclopamine is

produced by California corn lily.

Pregnant animals grazing on the

plant have cyclopic offspring like

this lamb.

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

Tertiary bronchi

Primary bronchioles

Terminal bronchioles

Respiratory bronchioles

Alveolar ducts

Alveolar sacs

Alveoli

Respiratory

airways

Conductive

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:

Stage 1 – Embryonic stage (4-7

weeks)

• Formation of the respiratory

diverticulum through formation of

tertiary bronchi

Stage 2 – Pseudoglandular stage (8-

16 weeks)

• Formation of the rest of the

conductive airway

• Stops after formation of the terminal

bronchioles

5 stages of lung development

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. Alveolar duct

2. Primary septum

3. Alveolar sac

4. Type I pneumocyte

5. Type II pneumocyte

6. Capillaries

1. Alveolar duct

2. Secondary septum

3. Alveolar sac

4. Type I pneumocyte

5. Type II pneumocyte

6. 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.