Respiratory Embryology Flashcards
What occurs at week 4-5 in development of the respiratory system?
Respiratory diverticulum forms and branches into left and right bronchial buds
Stem of the diverticulum will differentiate into trachea and larynx
Respiratory development begins at week 4 when respiratory diverticulum forms and branches into left and right bronchial buds. The stem of the diverticulum will differentiate into trachea and larynx during week 5.
What occurs at week 5-6 in development of the respiratory system?
Branching yields secondary bronchial buds, which represent future lung lobes
What occurs between week 6 and 7 in development of the respiratory system?
Branching yields tertiary bronchial buds, which represent future bronchopulmonary segments
At what week of development do the terminal bronchioles form? What other important developmental process has just been completed?
Week 16
Formation of pericardial sac is complete at this point
What events take place between week 16 and 28 in the development of the cardiopulm system?
Respiratory bronchioles form, surrounding mesenchyme becomes highly vascular; the first terminal sacs (primitive alveoli) form
Pleuroperitoneal membranes have closed off pericardioperitoneal canals; diaphragm begins to differentiate
At what point in development of the respiratory system do the terminal sacs begin to differentiate into mature alveoli? When are the alveoli fully mature?
At birth; alveoli will then continue to form through the eighth year of life
__________ _________ = median outgrowth that appears in the floor of the primitive pharynx
Laryngotracheal groove
The laryngoracheal groove is the median outgrowth that appears in the floor of the primitive pharynx. It will form the _________ _________, or lung bud which is the primodium of the _________ _________
Laryngotracheal diverticulum
Tracheobronchial tree
What is the embryologic origin of the pulmonary epithelium and glands of larynx, trachea, and bronchi?
Endoderm of laryngotracheal groove
What is the embryologic origin of the connective tissue, cartilage, and smooth muscle in the structures of the tracheobronchial tree, thus surrounding the foregut of the developing embryo?
Splanchnic mesoderm (from lateral plate)
During development of the lungs, the distal end of the laryngotracheal diverticulum (lung bud) forms the ________ ________, which grows in the ______ direction and bifurcates at day 26-28
Respiratory bud; ventrocaudal
After the respiratory buds grow ventrocaudally and bifurcate around day 26-28, they will undergo further branching. The branching pattern of the lung _________ is regulated by surrounding __________
Endoderm; mesoderm
How many orders of airways form after birth? How many rounds of branching does this require?
7 orders of airways form after birth
Goes through 16-17 rounds of branching
The primary bronchial buds are rudiments of what structures?
Lungs and primary bronchi
When do primary bronchial buds begin branching to form secondary bronchial buds?
During the 5th week of development
What structures to the secondary bronchial buds form?
Right: Superior, middle, inferior (3)
Left: Superior, inferior (2)
_________ bronchi form by the 7th week
Segmental
Segmental bronchi form by the 7th week. What structures have formed by 24 weeks?
Bronchopulmonary segments
By 24 weeks, the bronchopulmonary segments have formed. These consist of what 2 components?
What other structures have formed at this point?
Segmental bronchi + mesenchyme
Respiratory bronchioles have also formed
Maturation of the lung epithelium begins at 5-17 weeks with ____________ epithelium, which may appear similar to exocrine gands
Pseudoglandular
Maturation of the lung epithelium begins at 5-17 weeks with pseudoglandular epithelium, which may appear similar to exocrine gands. All major elements of the lung have formed, except which ones? Can the fetus survive at this point?
All major elements have formed except those involved with gas exchange, so the fetus cannot survive
Lung epithelium is pseudoglandular between 5-17 weeks. Pseudoglandular then overlaps with development of ________ epithelium between 16-25 weeks which is associated with vascularization of lung tissue
Canalicular
Lung tissue is canalicular between 16-25 weeks. What lung structures have formed at this point? Can the fetus survive?
Respiratory bronchioles
Primordial alveoli and sacs present (primitive alveoli)
+/- survival rates depending on thickness of these alveoli at birth (want them thin enough for adequate gas exchange)
During maturation of the lungs:
5-17 weeks = pseudoglandular
16-25 weeks = canalicular
What forms between 24 weeks-birth? Can the fetus survive?
Terminal sac
At this point numerous alveoli form, epithelium is thin with increased vascularization
Gas exchange can occur, so the fetus can survive
When the terminal sac forms between 24 weeks and birth, numerous alveoli form and epithelium is thin with increased vascularization. What 3 things are associated with this epithelium?
Type I pneumocytes
Type II pneumocytes
Lymphatic capillaries
During maturation of the lungs:
5-17 weeks = pseudoglandular
16-25 weeks = canalicular
24 weeks-birth = terminal sac
What is the next phase in lung development, occurring between 32 weeks and 8 years of age?
Alveolar
Formation of alveolocapillary membrane, primitive alveoli, and mature alveoli
T/F: approximately 5% of mature alveoli develop postnatally
False! About 95% of mature alveoli develop postnatally
Alveolar development is largely completed at what age?
3 years
[however, new alveoli are added until 8 years of age]
As the bronchi develop, ______ ______ is critical to the formation of cartilaginous bronchial plates, bronchial smooth muscle and CT, and pulmonary CT + capillaries
Splanchnic mesoderm
As the bronchi develop, the splanchnic mesoderm is critical to the formation of what 3 things?
Cartilaginous bronchial plates
Bronchial smooth muscle + CT
Pulmonary CT + capillaries
Lungs acquire a layer of ______ _______ from the splanchnic mesenchyme. With expansion, the lungs and pleural cavities grow in the _____ direction into the mesenchyme of the body wall, and are soon positioned close to the heart
Visceral pleura; caudal
Lungs acquire a layer of visceral pleura from the splanchnic mesenchyme. With expansion, the lungs and pleural cavities grow in the caudal direction into the mesenchyme of the body wall, and are soon positioned close to the heart.
The thoracic body wall becomes lined with a layer of parietal pleura which is derived from _______ _________
Somatic mesoderm (from lateral plate mesoderm)
** contrast with visceral pleura which is derived from splanchnic mesoderm (also from lateral plate mesoderm)
What is the space called between the parietal and visceral pleura?
Pleural cavity
The proximal end of the laryngotracheal diverticulum forms what 2 structures?
Trachea and larynx
The larynx opens into the pharynx via the _______; the passageway is located at the original point of evagination of the diverticulum.
Glottis
[note: the glottis eventually becomes associated with the vocal folds]
Structures between the trachea and lung have similar embryologic origin; the cartilage, CT, and smooth muscle of the trachea is derived from ______ ______, while the glands and epithelium are ________ derived
Splanchnic mesoderm
Endodermally
________ _______ = condition also known as “blind esophagus” where the esophagus contains a pouch that does not go anywhere. Food may become trapped –> infection risk, and there is diminished ability to maintain nutrition
Esophageal atresia
________ ________ = condition characterized by an abnormal connection between the trachea and esophagus
Tracheoesophageal fistula
What causes things like esophageal atresia and tracheoesophageal fistula?
Failure of the foregut endoderm to proliferate rapidly enough in relation to the rest of the embryo
Esophageal atresia and tracheoesophageal fistula are associated with aspiration of milk and other fluids into the lungs. They are also associated with _________, referring to excess amniotic fluid which then cannot enter the stomach/intestines for absorption and is not transferred to placenta for disposal
Polyhydramnios
________ ________ refers to the complete absence of a lung or lobe and accompanying bronchi; typically occurs unilaterally
Pulmonary agenesis
What causes pulmonary agenesis?
Respiratory bud fails to split into right and left bronchial buds, so only one lung structure develops unilaterally
________ ______ _______ are essential for normal lung development; their intermittent pattern conditions respiratory muscles and is used during fetal monitoring as a predictor of fetal outcome in preterm delivery
Fetal breathing movements (FBMs)
Fetal breathing movements are forceful enough to cause aspiration of _____ _____ which helps to stimulate lung development
Amniotic fluid
At birth, aeration of the lungs requires replacement of intra-alveolar fluid with air. In what 3 ways is this fluid cleared?
- Released from mouth/nose by pressure on the fetal thorax during vaginal delivery
- Pulmonary capillaries, arteries, and veins
- Lymphatics
____________ refers to insufficient amniotic fluid production which, when severe and chronic, can slow lung development
Oligohydramnios
Oligohydramnios may lead to ________ ________, refering to a restriction of the fetal thorax (from uterine pressure). The decreased hydraulic pressure on the lungs affects stretch receptors and lung growth
Pulmonary hypoplasia
What condition is characterized by rapid, labored breathing developing shortly after birth, affecting approximately 2% of neonates and accounting for 50-70% of deaths in premature infants?
Respiratory Distress Syndrome
What is the major cause of respiratory distress syndrome?
Surfactant deficiency
[Due to this deficiency, lungs are underinflated, alveoli contain a fluid that resembles a glassy membrane (hyaline membrane disease), and there are irreversible changes in the type II alveolar cells, making them incapable of producing surfactant]
What are some signs/symptoms of respiratory distress syndrome?
Tachypnea Nasal flaring Suprasternal, intercostal, or subcostal retractions Grunting Cyanosis
What condition is thought to be formed by the dilation of terminal bronchi due to disturbance in bronchial development during late fetal life?
Congenital lung cysts
What are congenital lung cysts filled with? What are some symptoms of congenital lung cysts?
Filled with fluid or air
May exhibit wheezing, cyanosis, difficulty breathing
What body cavity forms during the 4th week of embryonic development?
Intraembryonic coelom
The intraembryonic coelom forms during the 4th week of development. It is horseshoe shaped.
The cranial region represents the future ______ cavity
The caudal region represents the future ____ and _____ cavities
Pericardial
Pleural; peritoneal
The intraembryonic coelom is continuous with what body cavity?
Extraembryonic coelom (chorionic cavity)
Body folding (head fold) reshapes the intraembryonic coelom; the primitive pericardial cavity is now located cranially to the ______ _______. The heart is also repositioned and bulges into the pericardial cavity
Septum transversum
What 2 narrow canals lie dorsal to the septum transversum?
2 Pericardioperitoneal canals
What 2 caudal cavities are positioned where the intraembryonic and extraembryonic coeloms are continuous?
Peritoneal cavities
Initially, the lung bud is in open communication with the foregut. When the diverticulum expands caudally, however, 2 longitudinal ridges called _______ ______ separate it from the foregut.
Subsequently, when these ridges fuse to form the _______ _______
Tracheoesophageal ridges
Tracheoesophageal septum
The tracheoesophageal septum is important for dividing the forgut into a dorsal and ventral portion.
What important structures make up the dorsal and ventral portions formed by this septum?
Dorsal = esophagus
Ventral = trachea and lung buds
Once the tracheoesophageal septum separates the forgut into dorsal (esophagus) portion and ventral (trachea+lung buds) portion, what maintains communication between the respiratory primordium and the pharynx?
Laryngeal orifice
The lateral plate mesoderm divides into 2 layers as a result of the formation and coalescence of coelomic spaces within it.
The dorsal layer forms somatic mesoderm, which combines with surface ectoderm to form the ___________.
The ventral layer forms the splanchnic mesoderm, which combines with the underlying endoderm to form the __________.
Somatopleure
Splanchnopleure
[the space between these = the primitive body cavity]
_______ = fluid filled body cavity completely lined by tissue created from mesoderm
Coelom
Embryonic folding consists of cranial, lateral, and caudal edges of the embryonic disc brought together along the ventral midline. When does embryonic folding take place?
Week 4
During the process of embryonic folding, when ectoderm fuses at the ventral midline, a space is formed within the lateral plate mesoderm called the _______ _________
Intraembryonic coelom
The intraembryonic coelom gives rise to the _____ _______ that line the coelom
Serous membranes
_________ mesoderm coats the inner surface of the body wall.
_______ mesoderm ensheaths the gut tube.
Somatic
Splanchnic
Which specific coelom forms the embryonic body cavity?
Intraembryonic coelom
The intraembryonic coelom is divided into what 3 cavities during the 4th week?
1 Pericardial cavity
2 pericardioperitoneal canals
1 peritoneal cavity
Formation of the head fold relocates the heart and pericardial cavity ________ (anterior to foregut). At this point a definitive pericardial cavity has been established, but it remains open into the _______ _________
Ventrally
Pericardioperitoneal canals
The pericardial cavity initially remains open into the pericardioperitoneal canals. These are located lateral to the future _______; and dorsal to the ______ _______, which is a thick plate of mesodermal tissue occupying space between the thoracic cavity and stalk of yolk sac
Esophagus
Septum transversum
The septum transversum is a mesodermal structure that exists anterior to the umbilical vesicle. What is it a primordium for?
The central tendon of the diaphragm
[also provides block of mesoderm that forms CT of liver]
The septum transversum forms partitions in each pericardioperitoneal canal, separating what structures?
Pericardial cavity from the pleural cavities
Pleural cavities from the peritoneal cavity
Due to the growth of lung buds into the pericardioperitoneal canals, a pair of membranous ridges is produced.
The first develops cranially, superior to the lungs. What are these ridges called?
Pleuropericardial folds
Due to the growth of lung buds into the pericardioperitoneal canals, a pair of membranous ridges is produced.
The second develops caudally, inferior to the lungs. What are these ridges called?
Pleuroperitoneal folds
Due to the growth of lung buds into the pericardioperitoneal canals, a pair of membranous ridges is produced cranially (pleuropericardial folds) and caudally (pleuroperitoneal folds).
The pleuropericardial folds enlarge to become pleuropericardial membranes. What do these membranes form partitions around, and what do they contain?
Form partitions that separate the pericardial cavity and pleural cavities
Contain the common cardinal veins, which drain into the sinus venosus of the heart
The pleuropericardial membranes form partitions separating the pericardial cavity and pleural cavities. These contain the common cardinal veins, which drain into what structure?
Sinus venosus of the heart
The pleural cavities expand ventrally around the heart and extend into the body wall, splitting the mesenchyme into:
An outer layer that becomes the _______ _____
An inner layer that becomes the ______ ______
Thoracic wall
Fibrous pericardium
The pleural cavities expand ventrally around the heart and extend into the body wall, splitting the mesenchyme into an outer layer (thoracic wall) and an inner layer (fibrous pericardium). These two structures form the ______ ______
Primordial mediastinum
Due to the growth of lung buds into the pericardioperitoneal canals, a pair of membranous ridges is produced cranially (pleuropericardial folds) and caudally (pleuroperitoneal folds).
The pleuroperitoneal folds enlarge and project into the pericardioperitoneal canals, then become the pleuroperitoneal membranes.
The pleuroperitoneal membranes eventually partition what structures?
Pleural cavities from peritoneal cavity
The pericardioperitoneal canals grow ventrally to eventually fuse with the ______ ______, sealing them off.
Closure of the pericardioperitoneal canals is completed by week ____ of development and is characterized by definitive separation of the _______ and _______ cavities
Septum transversum
7
Pleural; peritoneal
During what weeks of development does the diaphragm develop?
Weeks 4-5
The diaphragm is formed by what 4 embryologic components?
Septum transversum
Pleuroperitoneal membranes
Dorsal esophageal mesenchyme
Muscular ingrowth from lateral body walls
The diaphragm is innervated by spinal nerves from ______, which join together to form the ______ nerve
C3-5
Phrenic
What pathological condition is characterized by viscera bulging into the pleural cavity prior to birth?
Congenital diaphragmatic hernia
Which side of the body is typically impacted by congenital diaphragmatic hernia?
80% of cases are left-sided
95% found posterolaterally
The lungs are the most impacted organ with a congenital diaphragmatic hernia. What affect does this type of hernia have on the lungs, and what secondary condition might this lead to?
Diaphragmatic hernia may compress the lung leading to pulmonary hypoplasia
A 26 y/o female with polyhydramnios gave birth to a full term male. Immediately after birth, the infant presented with excessive secretions that cause drooling, choking, coughing, and gagging. He also showed signs of respiratory distress, was unable to feed, and had an abnormal chest x-ray. Which of the following is his most likely diagnosis?
A. Esophageal atresia B. Tracheoesophageal fistula C. Respiratory distress syndrome D. Congenital lung cysts E. Congenital diaphragmatic hernia
B. Tracheoesophageal fistula
A full-term newborn infant was suffering from respiratory distress after birth. Examination reveals cyanosis, barrel-shaped chest, scaphoid appearing abdomen, and absence of breath sounds on one side. Imaging studies reveal lung hypoplasia. Which of the following is your most likely diagnosis?
A. Esophageal atresia B. Tracheoesophageal fistula C. Respiratory distress syndrome D. Congenital lung cysts E. Congenital diaphragmatic hernia
E. Congenital diaphragmatic hernia
A premature infant developed rapid, shallow respiration shortly after birth. This was accompanied by nasal flaring, subcostal retractions, and grunting. Imaging revealed a bell-shaped thorax, reduced lung volume, and lung parenchyma with a granular pattern. Which of the following is your most likely diagnosis?
A. Esophageal atresia B. Tracheoesophageal fistula C. Respiratory distress syndrome D. Congenital lung cysts E. Congenital diaphragmatic hernia
C. Respiratory distress syndrome
A 26 y/o female with polyhydramnios gave birth to a full term male. Immediately after birth, the infant presented with excessive secretions that cause drooling, choking, coughing, and gagging. He also showed signs of respiratory distress, was unable to feed, and had an abnormal chest x-ray.
The infant was diagnosed with tracheoesophageal fistula. At what stage/week did this occur, and what is the underlying embryologic mechanism?
Likely occurred during week 4 with failure of tracheoesophageal septum to divide the foregut properly
[Tracheoesophageal fistulas are the result of abnormal connections between the trachea and esophagus. This issue develops from improper division of the foregut by the tracheoesophageal septum. It is generally associated with esophageal atresia and polyhydramnios]
A full-term newborn infant was suffering from respiratory distress after birth. Examination reveals cyanosis, barrel-shaped chest, scaphoid appearing abdomen, and absence of breath sounds on one side. Imaging studies reveal lung hypoplasia.
The infant is diagnosed with a congenital diaphragmatic hernia. At what stage/week did this occur, and what is the underlying embryologic mechanism?
Likely occurred during weeks 4-5 due to failure of pleuroperitoneal membrane to develop or fuse with the other components of the diaphragm
A premature infant developed rapid, shallow respiration shortly after birth. This was accompanied by nasal flaring, subcostal retractions, and grunting. Imaging revealed a bell-shaped thorax, reduced lung volume, and lung parenchyma with a granular pattern.
The infant is diagnosed with respiratory distress syndrome. What is the most likely underlying cause?
Surfactant deficiency
A premature infant developed rapid, shallow respiration shortly after birth. This was accompanied by nasal flaring, subcostal retractions, and grunting. Imaging revealed a bell-shaped thorax, reduced lung volume, and lung parenchyma with a granular pattern.
The infant is diagnosed with respiratory distress syndrome. At what stage/week did this occur, and what is the underlying embryologic mechanism?
Most likely occurred prior to terminal sac stage (week 24) when type II pneumocytes begin producing surfactant
This infant likely has a surfactant deficiency, meaning that the lungs are underinflated, and alveoli contain a fluid resembling glassy membrane (hyaline membrane disease). With irreversible changes in type II alveolar cells, they are unable to produce surfactant.