11-1: 11/28: Lung Structure And Development

Front 1

What structures comprise the conducting zone of the respiratory system?

Function?

Back 1

Trachea
Main stem bronchi
Bronchi (12-23)
Bronchioles (no cartilage)
Terminal Bronchioles

Functions:
Conduct and condition air

Front 2

What structures comprise the terminal respiratory unit?

Function?

Back 2

Respiratory bronchioles
Alveolar Ducts
Alveolar Sacs

Fn: Gas Exchange

Front 3

Alveolar Type I Cell:
Shape
Distribution
Function

Back 3

Type I Cells:
Flattened
Cover 95% of alveolar surface (but only make up 40% of alveolar lining cells)
Main fn: Gas exchange

Front 4

Alveolar Type II Cell:
Shape
Distribution
Function

Back 4

Type II Cells:
Cuboidal
Cover only 5% of alveolar surface (But make up 60% of alveolar lining cells)
Fn: Source of surfactant, progenitor of Type I Cells

Front 5

The terminal respiratory unit is also known as the ______.

Back 5

Acinus

Front 6

List the stages of lung development, the weeks in which they occur, and events that take place.

Back 6

Embryonal: 3-8wks; formation of lung bud, trachea, major/segmental bronchi

Pseudoglandular: 8-16 wks; formation of remaining conducting airways

Canalicular: 17-24wks; formation of acinus and vascular bed; epithelial flattening

Saccular: 24-36wks; increased complexity of resp saccules

Alveolar: 36wks-2/8 yrs; dev't of alveoli

Front 7

In which stages of lung development does branching morphogenesis occur?

Back 7

Embryonal, pseudoglandular

Front 8

In which stages of lung development does distal (acinar) lung remodeling occur?

Back 8

Canalicular, saccular, alveolar

Front 9

How is branching morphogenesis regulated in development?

Back 9

Crosstalk between epithelium (foregut endoderm) and mesenchyme (splanchnic mesoderm)

Mediated through: GF's (FGF-10), TFs (Shh), and ECM-related molecs

Front 10

What roles do FGF-10 and Shh play in branching morphogenesis?

Back 10

FGF-10 induces directional lung bud growth (chemotaxis)

As bud approaches chemotactic source of FGF-10, Shh is released from growing bud to downregulate FGF-10 expression (thus inhibition of chemoattraction), which results in cleft formation

Front 11

What is the role of TGF-beta1 in branching morphoegenesis?

Back 11

Induces synthesis of ECM components along epithelial-mesenchymal interface to prevent further budding (TGF-beta1 is released in response to FGF-10!)

Front 12

If FGF-10 expression is dampened during development, how does it lead to branching?

Back 12

Only the initial chemotactic center is dampened, FGF-10 expression is relocalized laterally, leading to new sources of chemoattractant; thus forming new distal branches.

Front 13

What is the effect of glucocorticoids on lung maturation?

Back 13

Accelerates lung maturation (antenatal steroids given to mothers at risk for preterm delivery)

Front 14

What is the effect of androgens on lung maturation?

Back 14

Delay lung maturation

Front 15

What is the effect of insulin/DM on lung maturation?

Back 15

Delay lung maturation

Higher incidence of respiratory disress syndrome in infants of diabetic mothers.

Front 16

What is lung hypoplasia?

Causes?

Back 16

Incomplete development of the lung; common (seen in 10% of neonatal autopsies)

Causes:
Space-occupying lesions (diaphragmatic hernia, chest wall abnmlts)

Olioghydramnios (premature rupture, renal cystic dz, renal agenesis)

Dec'd fetal respiratory mvmts (congenital neurological/neuromuscular disorders)

Front 17

What is normal lung weight/body weight ratio before 28 wks gestation? After 28 wks?

What does this ratio help assess?

Back 17

Normal before 28 weeks: >1.5%
After 28 weeks: >1.2%

Allows for assessment of lung hypoplasia

Front 18

How is architectural maturity of the lungs determined pathologically?

Back 18

Assessment of alveolar hypoplasia via RADIAL ALVEOLAR COUNT

Front 19

How is cellular maturity of the lungs determined?

How would you discern between immature and mature cellular structure?

Back 19

Cell maturity via cytodifferentiation of type II pneumocytes:

If immature, lots of glycogen present in Type II cells.

If mature, less glycogen, and presence of Lamellar Bodies (on EM)

Front 20

What does a Lecithin/sphingomyelin ratio determine? What's a normal ratio?

Back 20

L/S ratio assocd w/inc'd synthesis of surfactant, thus can estimate lung maturity with L/S ratio in amniotic fluid.

L/S ratio >2 means Lung maturity and low risk of RDS

Front 21

Bronchogenic Cysts:
Cause
Subtypes (which is more prominent?)
Presentation

Back 21

Bronchogenic Cysts:
Caused by abnl budding of ventral diverticulum during dev't

Subtypes: Mediastinal (85%), Intrapulmonary (15%)

Presentation: Most asyx, and found incidentally. May become infected (cough, fvr, abscess)

Front 22

Congenital Pulmonary Airway Malformation:
What is it?
Presentation
Pathology (General)
Type I vs Type II

Back 22

Congenital hamartoma (benign neoplasm) showing abnl prolifern in distal bronchial and parenchymal tissue

Presentation: stillbirth, RDS, hydrops, NON-PULM ANOMALIES

Path: proliferation of structures ~terminal bronchioles, polypoid (~polyp) projections of immature cuboidal cells, NO inflammn

CPAM Type I: large cyst-type, most common, good prognosis

CPAM Type II: small to medium cyst-type: less common; assocd w/other anomalies

Front 23

Lobar Sequestration:
General
Intralobar vs Extralobar (general, route of venous drainage, presentation)

Back 23

Lobes or segments of lung tissue that don't communicate w/tracheobronchial tree through bronchus; supplied by anomalous systemic artery (aorta)

Intralobar: within visceral pleura; drains via pulmonary veins; most common, presents in adulthood (recurrent infections)

Extralobar: external to lung (thorax, mediastinum, abdomen); drains via systemic veins; presents in childhood as cyanosis, dyspnea

Front 24

What does the Law of Laplace state?

Back 24

Inverse relationship between surface tension and alveolar radius; thus, a small alveolus will experience greater inward force than a large alveolus if surface tensions are equal

Front 25

Surfactant is 90% _____ and 10% _____.

Role of each of these components?

Back 25

90% lipid (DPPC): reduces surface tension

10% proteins (Apoproteins):
SP-A/D: hphilic, immune-defense
SP-B/C: hphobic, surface-active

Front 26

What triggers the release of surfactant? How is it cleared?

Back 26

Secreted from Type II cells in response to lung expansion, hyper-ventilation, beta-agonists

Reuptake by Type II cells (active process) and phagocytosis by alveolar macs

Front 27

When in gestation is surfactant produced?

Back 27

Begins early in third trimester, but adult pool size not attained until 35-36 weeks

Front 28

Neonatal Respiratory Distress Syndrome:
General
Cause

Back 28

Alveolar collapse and formation of hyaline membranes (necrotic cells + fibrin due to hypoperfusion and cell injury) in terminal resp units (most common in infants <28 weeks)

Cause: Deficiency of pulm surfactant (usually due to immaturity of lungs), leading to atelectasis

Front 29

What are the major risk factors for hyaline membrane disease?

Back 29

Hyaline Membrane Dz = RDS

Risk factors:
Prematurity
Perinatal Asphyxia
C-section
DM

Front 30

Bronchopulmonary Dysplasia:
General
Mechanism
Long-Term Sequelae

Back 30

Lung dz in infants under 32 weeks who require at least 28 days O2 tx

Mech is multifactorial: infection/inflammn, cytokines, hypoxia, mechanical ventilation (stretch)

Sequelae:
Honeycomb lung, tracheal stenosis, apneic spells, pulm infections, emphysema