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Transcript
11. ORGANOGENESIS IN GASTROINTESTINAL AND
RESPIRATORY SYSTEMS
Major Period of Organogenesis
Do I need to know this?
Splanchnic mesoderm in
GI tract development
Neural crest cells and mesodermal roles in
tissue and organ development in the GI tract
Some neurons
derive from neural
crest cells
Other pacemaker
cells including
Interstitial Cells of
Cajal (ICC) come
from mesoderm
Early gut tube with emphasis on septum transversum
Distinct vascularization of foregut midgut and hindgut
Origins of the respiratory tract: a dorsal-ventral patterning problem
Left-side view
Ventral view
Ventral view
Branching mechanisms in the lung regulated
by FGF and Sonic hedgehog signaling
Figure 22-92a Molecular Biology of the Cell (© Garland Science 2008)
“Normal neonatal chest radiograph”
Lung maturation
A crucial event in the maturation of lungs and pulmonary
function is the onset of surfactant production.
Surfactant is a mixture of phospholipids, neutral lipids and proteins
synthesized by type II pneumocytes by the end of gestation.
60% of surfactant is dipalmitoylphosphatidylcholine (DPPC), also
Called dipalmitoyllecithin.
Surfactant protein A (SP-A), surfactant protein B (SP-B),
surfactant protein C (SP-C) and surfactant protein D (SP-D)
are evolutionarily conserved and expressed in mice and man.
During the third trimester the fetal lung synthesizes primarily
sphingomyelin, and lung cells convert the majority of their stored
glycogen to fatty acids and then to dipalmitoyllecithin.
Fetal lung maturity can be determined by measuring the
ratio of lecithin to sphingomyelin (L/S ratio) in the amniotic
fluid. An L/S ratio less than 2.0 indicates a potential risk of
RDS. The risk is nearly 75-80% when the L/S ratio is 1.5.
Surfactant functions and RDS
The role of surfactant in gas exchange includes lowering of surface
tension at the air water interface to prevent collapse of terminal
alveoli and small airways, and to prevent movement of fluid into
the alveolus.
Other roles of surfactant are thought to include enhancement of
mucous clearance and stimulation of host lung immunological
defences.
Small airway and alveolar collapse can result in infant
respiratory distress syndrome (RDS), also called hyaline membrane
disease.
Chest X-ray in respiratory distress syndrome
Surfactant production can be induced by administration of
corticosteroids to the mother (over a period of about 24 hours) prior
to delivery of infants between 26-34 weeks.
Post-natally, aerosolized surfactant can be administered to infants
with suspected RDS. From the 1960’s until recently, the protein
components of surfactant therapy were derived from animal extracts
(bovine or porcine). Recombinant surfactant protein is now
the standard. Surfactant therapy carries some risk, however,
which will be discussed in the upcoming lecture on perinatal development
and birth.
In rare instances, a fatal homozygous recessive familial condition
results in deficiency of the protein components of surfactant,
like surfactant protein B (hereditary surfactant protein B deficiency).
This deficiency also affects processing of SP-B and phospholipids,
both in experimental mouse models and in humans. Bile breaks down
lipids (as you will learn) so aspiration of bile can lead to reduced
surfactant function. You will learn more about surfactant in
pulmonary physiology and in lectures on perinatal development
and birth.
Rotation and growth of the GI tract to achieve
asymmetry: stomach and duodenum
Transverse view of the GI tract at the
level of the stomach
Swallowing, amniotic fluid, polyhydramnios, oligohydramnios
Polyhydramnios - too much
Oligohydramnios - too little
Regulation of blood and immune system by GI organs; the spleen
Radiographic view of the normal upper GI tract with ingested contrast agent
FGF signaling directs ‘bi-potent’ endoderm toward liver
and away from pancreas development
Normal pancreas development
Normal pancreas development
Pancreas functions

Exocrine: digestive enzymes (acini) and bicarbonate (ducts)

Endocrine: islet hormones, principally insulin and glucagon

Note relation of pancreatic duct to liver bile duct
Case history
Radiographic view of the GI tract with ingested contrast agent in this case
The intestines constitute the largest immune organ
and one of the largest endocrine organs; so big they
‘herniate’ transiently while turning: ‘physiological herniation’
Views of the normal appendix and pathology including appendicitis
Normal gut turning
Enterohepatic bile cycle
Pyloric sphincter stenosis