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SMP - Cardiopulmonary Exam 2 > Lecture 20 - Embryology of the Respiratory System > Flashcards

Lecture 20 - Embryology of the Respiratory System Flashcards

1
Q

Do the lungs occupy most of the space in the thorax?

A

YUP

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2
Q

Where is the trachea located?

A

Superior mediastinum, anterior to the esophagus

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3
Q

At what level does the trachea bifurcate?

A

T4/T5 aka the sternal angle

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4
Q

What do the esophagus and trachea share?

A

Common border = the trachealis muscle on the trachea’s posterior wall and the anterior wall of the esophagus

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5
Q

What meets the trachealis muscle?

A

16-20 incomplete cartilaginous rings (C-shaped)

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6
Q

How many times do the bronchi bifurcate in utero? What about postpartum?

A

23 times in utero

4 times postpartum

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7
Q

Do most alveoli form before or after birth?

A

AFTER birth (8.3 million vs 134 million)

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8
Q

What is the hilum of the lung?

A

The point where the root of the lung joins the medial surface of the lung

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9
Q

What is the root of the lung?

A

Sleeve-like covering made of reflections of the mediastinal pleura onto the mediastinum that pass between the lung and mediastinum

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10
Q

How do the diameters and overall surface area of the respiratory system change as the bronchi move distally?

A

Diameters decrease and overall surface area increases

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11
Q

What is the total epithelial surface area of the gas exchange in the lungs?

A

70 m^2

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12
Q

What is the total length of all of the capillaries in the lungs?

A

Almost 1,000 km

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13
Q

How do the walls of the bronchi change from proximal to distal? What do they become?

A

Supportive cartilage is replaced by smooth muscle under autonomic control until the walls are completely void of cartilage = bronchioles

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14
Q

What is the terminus of the bronchiole called?

A

Acinus

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15
Q

Describe how cephalocaudal folding contributes to the development of the lungs.

A

3-layered bilaminar disc undergoes cephalocaudal folding which forms the gut tube from the yolk sac where the lungs start to develop:

  1. The superior amniotic cavity enlarges relative to the yolk sac to form pockets of endoderm that pivot around a fixed anterior end (the oralpharyngeal membrane) and fixed posterior end (the cloacal membrane)
  2. Overlapping endoderm forms the foregut, midgut, and hindgut (the endoderm of the territory rostral to the oropharyngeal membrane becomes incorporated into the anterior ventral body wall as the blind-ending foregut)
  3. Foregut is subdivided into the pharyngeal gut in the head/neck area and the foregut
  4. Developing lungs form from the most anterior/cranial border of the foregut
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16
Q

At point in gestation do the lungs develop?

A

During the 4th week

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17
Q

Which mesoderm is associated with the yolk sac and forms the lungs?

A

Splanchnic/visceral lateral plate mesoderm

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18
Q

How is the esophagus formed?

A

Lateral folding of the splanchnic/visceral lateral plate mesoderm around the yolk sac

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19
Q

Describe the first step of lower airways development. What appears in conjunction?

A

Formation of the ventral midline respiratory diverticulum, composed of epithelial endoderm surrounded by splanchnic lateral plate mesoderm/mesenchyme. It grows quickly, and soon bifurcates into two laterally positioned lung buds (R and L)

In conjunction: the advent of the laryngotracheal groove on the ventral aspect of the caudal pharynx.

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20
Q

What does the respiratory system consist of? Describe each.

A
  1. Upper airways (nasal passages, pharynx)
  2. Larynx (which marks the dividing point of the two respiratory regions)
  3. Lower airways (trachea, bronchi, and lungs)
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21
Q

What is the first (most cranial) derivative of the foregut?

A

The respiratory diverticulum

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22
Q

What are the 4 parts of the embryonic gut tube?

A
  1. Pharyngeal gut
  2. Foregut
  3. Midgut
  4. Hindgut
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23
Q

What is another name for the the ventral midline respiratory diverticulum?

A

Tracheobronchial diverticulum

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24
Q

What will the splanchnic lateral plate mesoderm of the respiratory diverticulum give rise to?

A

The respiratory capillaries surrounding the alveoli

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25
Q

What will the endoderm of the respiratory diverticulum give rise to?

A

The surface for gas exchange in the alveoli

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26
Q

What is the ONLY asymmetrical bifurcation of the bronchial buds? What does this correspond to?

A

The second one forming secondary bronchial buds: 3 on the right side (3 right lobes) and 2 on the left (2 left lobes)

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27
Q

Describe how the trachea and esophagus separate.

A

Formation of the tracheo-espohageal septum to separate the respiratory diverticulum from the gut tube by being gradually pinched in from both sides inferiorly to the larynx

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28
Q

What does failure of the tracheo-espohageal septum to form properly lead to? Which is most common? Treatment?

A

Leads to a variety of malformations that allow for either:

  1. ***Aberrant connections between the digestive tube and the posterior aspect of trachea = tracheo-esophageal fistula (+ possible esophageal atresia depending on which portion of the esophagus is attached to the trachea)
  2. Discontinuities of the digestive tube
  3. Communication between esophagus and trachea (both continuous) with 2 tracheo-esophageal fistulae

Easily fixed with surgery if noticed in time

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29
Q

What are the anterior and posterior walls of the tracheo-esophaheal septum made of?

A
  1. Anterior wall = trachealis muscle

2. Posterior wall = the anterior wall of the esophagus

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30
Q

What is the larynx?

A

Common pathway to the esophagus and trachea

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31
Q

What is the branching pattern of the lung buds controlled by? What does this mean?

A

Branching pattern (aka where the divisions will take place) is controlled by the mesenchyme of the lung buds of the foregut

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32
Q

What is the functionality of the lung buds controlled by? What does this mean?

A

Functionality is determined by the epithelium of endoderm of the lung buds of the foregut (whether it will become a respiratory bronchiole or alveolus)

33
Q

What is early lung bud development characterized by? How does this evolve and when?

A

In weeks 26-36 there is a small presumptive air space and large mesenchymal component

After week 36 aka at end of saccular stage, the mesenchyme starts to degenerate as the airspace within the epithelium increases and the epithelial cells flatten to increase surface area and decrease membrane thickness to increase the rate of diffusion

34
Q

Describe the control of the lung bud branching by the mesenchyme.

A
  1. The mesenchyme surrounding each tip secretes FGF-10 that stimulates mitosis of the epithelium
  2. The cells of the epithelium start to divide, and the lung bud grows in length
  3. The surrounding epithelial cells around the tip receive less concentrated amounts of FGF-10, so they do not divide as rapidly vs the large concentration of FGF-10 at the
    tip stimulates the epithelial cells to start secreting BMP-4 and Shh
  4. When these two molecules reach a high enough concentration at the tip, they block stimulation of epithelial cell division
  5. Simultaneously with cessation of division, the epithelium begins to secrete VEGF, which invites the formation of capillaries near the branching points via vasculogenesis
35
Q

How does Shh at the tip of the lung bud contribute to the cessation of cell division?

A
  1. Inhibits the release of FGF-10 from the mesenchyme
  2. Stimulates mesenchyme to secrete TGF-β, which stimulates the localized secretion of extracellular matrix molecules (fibronectin and collagens I, III, IV) by the mesenchyme => these ECM molecules stop tip growth due to the dense connective tissue being laid down and allow formation of new tips adjacent to the distal edges of the ECM rich area.
36
Q

How does BMP-4 at the tip of the lung bud contribute to the cessation of cell division?

A

Inhibits the release of FGF-10 from the mesenchyme

37
Q

What does FGF stand for?

A

Fibroblast growth factor

38
Q

What does BMP stand for?

A

Bone morphogenic protein

39
Q

What does Shh stand for?

A

Sonic hedgehog

40
Q

Does the lung bud bifurcation occurring after birth occur through the same mechanism than in utero?

A

YUP

41
Q

Does the respiratory vascular system develop in concert with the branching of the respiratory diverticula?

A

YUP

42
Q

What does it mean for respiratory epithelial cells to have polarity?

A

It means that the cells know the difference between their luminal and basal surfaces

43
Q

Describe how the polarity of respiratory epithelial cells work.

A

Mesenchyme secretes epimorphin which signals the location of the basal region of the epithelial cells (aka the location of the nucleus)

44
Q

Toward which surface of the respiratory epithelial cells are their nuclei located?

A

Basal surface

45
Q

How do epithelial cells know to remain in sheets or tubes?

A

Mesenchyme in the straight tube portions of the airways produces tenascin and syndecan causing the epithelial cells to flatten

In the branching areas and globular areas these are not secreted by the mesenchyme

46
Q

How do the mesenchymal controls relate to lung tumors?

A

A lot of lung tumors lack these organizational controls

47
Q

In what manner does the maturation of the lungs occur? Describe this.

A

Stages described by morphological characteristics which overlap due to the ongoing branching of the duct system of the lungs

48
Q

What are the 5 stages of lung development?

A
  1. Embryonic = lung buds arise from the foregut & branch 3 times to form primordia of 2 lungs, 5 lobes, & the broncho-pulmonary segments
  2. Pseudoglandular = respiratory trees branch 14 more times to form terminal bronchioles
  3. Canalicular = terminal bronchioles divide into 2+ respiratory bronchioles and respiratory vasculature begins to develop
  4. Saccular = respiratory bronchioles subdivide into terminal sacs that are continuously produced into childhood and type I and II alveolar cells appear (aka alveolar ducts)
  5. Alveolar = alveoli develop and mature with GREAT increase in surface area
49
Q

Do all animals have the same 5 stages of lung development?

A

Yes, but the time spent within each stage varies from species to species

50
Q

At what lung development stage is surfactant produced? When exactly?

A

Starts at saccular stage at week 25 and continues through the alveolar stage

51
Q

What is another name for the saccular stage of lung development?

A

Terminal sac stage

52
Q

What are the 2 types of alveolar cells? Role of each?

A
  1. Type I = gas exchange

2. Type II = secretory

53
Q

What stages of lung development does the fetal period include?

A

2 to 5

54
Q

Purpose of surfactant?

A

Decrease surface tension so that the alveoli do not collapse during expiration

55
Q

At what lung development stage does the formation of the air-blood barrier occur?

A

Canalicular

56
Q

What stages of lung development does organogenesis include?

A

1 and 2

57
Q

What stages of lung development does differentiation include?

A

3 to 5

58
Q

Histologically, what does the pseudoglandular stage of lung tissue look like?

A

Salivary glands

59
Q

Histologically, what does the saccular stage of lung tissue look like?

A

Patient with emphysema because not much surface area

60
Q

What % of the volume of air-filled alveoli after birth is comprised by the fluid-filled alveoli in-utero?

A

60%

61
Q

What is a diaphragmatic hernia? How does it affect lung development? Treatment?

A

Hole in the left diaphragm causing a part of the thorax to be occupied by the developing GIT which competes with the developing respiratory system for space in the thorax needed for lung expansion and development => left lung (or both!) cannot properly develop => may not have enough alveoli to support life at birth

Treatments:

  • Postpartum treatment of the hernia may leave the the lungs hypoplastic and immature and survival is NOT certain
  • Earlier intervention through in utero laparoscopic surgeries allows the lung to develop fully and offers a better prognosis
62
Q

What would happen if there was a right side diaphragmatic hernia?

A

Nada because the hole would be covered by the liver

63
Q

Why are infants so pudgy?

A

Need extra surface area in GIT because villi not fully developed to absorb nutrients so intestines bulge out on each side of the abdomen

64
Q

How many alveoli in 1 cubic millimeter?

A

170

65
Q

What are the 3 layers of the alveolar walls? List from inner to outer.

A
  1. Epithelium
  2. Interstitium
  3. Endothelium
66
Q

How do the 3 layers of the alveoli evolve postnatally?

A

Interstitium (aka mesenchyme) gets much thinner meaning the alveolar cells flatten to allow for more efficient gas exchange

67
Q

To what do the capillary walls appose?

A

The alveolar epithelium

68
Q

What is another name for the alveolar interstitium?

A

The stroma

69
Q

How does the increase in surface area of the alveoli compare to that of the capillaries?

A

They are the same

70
Q

When does the critical period alveolar development happen in rats? When is alveolar development completed?

A

4 to 14 days after birth

Completed 3 weeks after birth

71
Q

When does the alveolar development happen in monkeys? When is alveolar development completed?

A

Happens entirely in utero

Completed at birth

72
Q

When is the critical period of alveolar development in humans? When is alveolar development completed?

A

Birth to 2 years

6-8 yo

73
Q

At what stage of lung development does birth happen in humans?

A

At the end of the saccular stage

74
Q

At what stage of lung development does birth happen in monkeys?

A

Toward the end of the alveolar stage

75
Q

At what stage of lung development does birth happen in rats?

A

Toward the beginning of the canalicular stage

76
Q

What is the critical factor in species selection for models of the human pediatric lung?

A

Timing of alveolar development

77
Q

Do species differ with regard to lung maturity at birth?

A

YUP

78
Q

What fraction of the adult number of alveoli are present at birth?

A

1/8 – 1/6 of the adult number of alveoli are present

79
Q

By what age are most alveoli formed in humans?

A

2

SMP - Cardiopulmonary Exam 2 (15 decks)

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