Respiratory Flashcards
(138 cards)
1
Q
Fetal Lung Fluid
A
Lung spaces filled with fluid due to net chloride influx into lungs
Periodic laryngeal movements allow exit of fluid into amniotic sac
Pressure gradient 3-5 cmH2O across larynx
2
Q
Channels involved in secretion of FLF (into alveoli)
A
Na/K/2Cl transporter Chloride channels (ClC2, ClCN2)
3
Q
Channels involved in absorption of FLF
A
Epithelial Na channel (ENaC)
Na/K-ATPase
4
Q
Composition of fetal lung fluid
A
High Cl (150) Low pH (6.27) Low protein (0.03)
5
Q
Clearance of FLF postnatally
A

35% cleared
- lung distention (incr transpulmonary pressure)
- increased lymphatic oncotic pressure a/w low fetal alveolar protein

6
Q
Sodium channels (FLF)
A
ENaC on apical surface - Bring sodium into the cell from alveoli
Na/K-ATPase - allow sodium to leave cell and enter interstitium
Water follows sodium out of alveoli and into interstitial space

7
Q
Fetal breathing
A
Discrete episodes that resemble REM sleep and periods of low-voltage cortical activity
During later half of gestation 40-50% FBM alternating with apnea
No FBM = reduction and lung volume
8
Q
Bradycardia after delivery
A
Due to lack of pulmonary stretch
Asphyxia -> hypoxia -> carotid chemoreceptor activation -> bradycardia
Periglottic stimulation activates laryngeal reflex
9
Q
Lung inflation in the DR
A
Immediate increase in HR and BP
Gradually: establishes FRC, improves pulmonary and blood flow, improves gas exchange
10
Q
Hering Breuer reflex
A
Lung overinflation leads to cessation of inspiration (apnea)
Pulm stretch receptors -> vagus
11
Q
Paradoxical reflex of Head
A
Inhibition of Hering Breuer reflex results in extended inspiration
Periodic deep sighs = initial newborn breaths
12
Q
J receptor reflex
A
Juxtacapillary receptors -> rapid, shallow breathing (TTN)
13
Q
Laryngeal chemoreflex
A
Age related response to stimulators of larynx
Response: hypertension, bradycardia, swallowing, apnea
Stimulus: water, milk, suction catheter
Enhanced by sedation and hypoxemia
14
Q
Carotid body reflex
A
Stimulus: hypoxemia (not hypoxia)
Response: initial increase in ventilation, followed by depression
Leads to peripheral vasoconstriction, stimulation of breathing, vagal (bradycardia)

15
Q
Distal esophageal reflex
A
Afferent: vagal nerve
Stimulus: irritation of distal esophagus
Response: laryngospasm and stridor
16
Q
Lung expansion and pulmonary vasodilation
A
Lung aeration -> increased oxygen and pH -> Vasodilation
NO, PGs further increase pulmonary blood flow
Stimulates FLF clearance and surfactant release
17
Q
Diving reflex
A
Response to asphyxia
Redistribution of cardiac output to heart, brain, adrenals
High PVR with R to L shunting
Increase in BP followed by hypotension
18
Q
Nitric oxide
A
Activation of guanylyl cyclase-> increased CGMP -> K channels -> pulmonary vasodilation
19
Q
Sildenafil
A
Inhibits PDE5 to prevent degradation of cGMP
20
Q
At end of which stage of lung development is the lung considered viable?
A
Canalicular
21
Q
Late stages of lung development
A
Alveolar and microvascular
- secondary crests
- capillary bilayer
22
Q
Timing of lung development stages
A
Embryonic: 0-6 weeks Pseudoglandular: 6-16 weeks Canalicular: 16-26 weeks Saccular: 26-36 weeks Alveolar and vascular: 36 weeks to 3-5 years
23
Q
Embryonic phase
A
Ventral lung buds off of esophagus at 4 weeks
Progressive elongation & dichotomous branching to form proximal airway
Pulmonary vascular development from 6th aortic arch
Coincides with development of kidneys
24
Q
Pseudoglandular phase
A
Branching continues
Trachea & segmental bronchi by 7 weeks
Closure of pleuroperitoneal folds at 7 weeks (CDH)
By 16 weeks all bronchial divisions are done (24 total)
25
Canalicular phase
Completion of conducting airways through terminal bronchioles
Rudimentary gas exchange units
26
Saccular phase
Gas exchange enabled by alveolar capillary membrane by 24 weeks
Expanding surface areas
Double capillary network
27
Alveolar phase
True alveoli appear at 36 weeks
Expansion of surface area via formation of septae or secondary crests
Postnatal alveolar growth for 3-5 years
28
Vascular phase of lung development
Birth to 3 years
Micro vascular maturation with single capillary bed
Late alveolarization 2-20 years
29
Early mediators of lung development
FGF 10, 9, 2 (fibroblast growth factor)
Sonic hedgehog (SHH)
Bone morphogenetic protein (BMP)
30
Fibroblast growth factor (FGF)
Polypeptide ligand
Works with tyrosine kinase receptor (FGF-R)
FGF 10 initiates primary branching

31
Mediators of lung development (C & S)
FGF1, FGF7, keratinocyte growth factor
TGFB super family: Regulates cell proliferation, differentiation, migration, and extracellular matrix formation
Linked to glucocorticoid signaling -> maturational effect of betamethasone on type 2 cells
32
Morphogens
Concentration gradients to give different developmental signals to growing tissue
33
Transcription factors in lung development
T-Box
FOX
HOX
TITF1
34
What leads to left-right asymmetry during cardiac development?
Lefty 1
Lefty 2
Nodal
Defects in these can lead to transposition, situs inversus
35
Vascular development of lungs
Vascular endothelial growth factor (VEGF)
| FLT1, FLK1 (high affinity receptors)
36
Mesenchyme
Development of lungs regulated by mesenchyme
| Removal arrests branching
37
Physical mediators of lung development
Lung fluid: promotes growth through chronic stretch
FBM: increased pressure when coupled with upper airway contractions
Peristaltic airway contractions: pressure on distal buds
38
Vitamin A and lung development
No vitamin A -> tracheal stenosis & pulmonary agenesis
39
Inhibition of alveolarization
```
Mechanical ventilation of preterm lungs
Glucocorticoids, insulin, PKC
Inflammatory cytokines (TGF-a, TNF-a, IL11, IL6
Hyperoxia or hypoxia
Poor nutrition
```
40
Abnormal development in embryonic phase
```
Atresias (laryngeal, esophageal, tracheal)
Bronchogenic cysts
TEF
Pulmonary agenesis/aplasia
Pulmonary sequestration
```
41
Abnormal development in pseudoglandular phase
```
Renal agenesis -> pulmonary hypoplasia
CPAM
Pulmonary lymphangiectasia
CDH
Tracheo/bronchomalacia
```
42
Abnormal development in cannalicular phase
Renal dysplasia and pulmonary hypoplasia
Alveolar capillary dysplasia
Surfactant deficiency
43
Abnormal development in saccular phase
Oligohydramnios and pulmonary hypoplasia
Alveolar capillary dysplasia
Surfactant deficiency
44
Abnormal development in alveolar phase
Lobar emphysema
Pulmonary hypertension
Surfactant deficiency
45
Tracheoesophageal fistula
M >> F
1:2500 births
Due to incomplete fusion of TE folds in embryonic phase
Five types
46
Bronchopulmonary sequestration
```
Mass of abnormal pulmonary tissue
Not connected to tracheobronchial tree
Blood supply from aorta
No gas exchange
COMPLETELY ABNORMAL
```
47
Intralobular BPS
Within visceral pleural lining of lobe, most often LLL
| Present with recurrent pulmonary infections
48
Extralobular BPS
Outside pleural lining, has own pleural sac
Associated with CDH
Most asymptomatic, some become infected
49
Bronchogenic cyst
Abnormal budding & branching of tracheobronchial tree
Most in mediastinal area
Neonates there can be a one-way valve between the cyst and the bronchial tree
Can get rapid expansion & CV compromise/death
Can fill with serous fluid and enlarge over time
On chest x-ray there is no lung parenchyma appears clear dark/black
50
Congenital lobar emphysema
Usually upper/middle lobe
Becomes overinflated and causes compression of other lobes/mediastinum
Most cases caused by partial bronchial obstruction
- extrinsic: pulmonary vessels, excessive pulmonary flow
- intrinsic: defects in bronchial cartilage leading to collapse and distal air trapping
51
Pulmonary aplasia
In embryonic phase - lung bud fails to partition
| Only rudimentary bronchi are present which end in a blind pouch
52
Lung volume in lung hypoplasia
<2/3 of normal lung volume
53
Causes of pulmonary hypoplasia
```
Renal agenesis/dysplasia
Urinary outlet obstruction
Anhydramnios/PROM
CDH
Large pleural effusions
Neuromuscular abnormalities
Aneuploidy
```
54
Bronchiolar and alveolar cysts
```
Communicate with proximal branches of bronchiolar tree and alveolar ducts
Restricted to single lobe, well defined
Fluid +/- Air filled
R>L lung
Lower lobes>upper lobes
```
55
CPAM
Lung immaturity and malformation of airways/lung parenchyma
25% of all congenital lung lesions
5 types - type 1 most common (>1 cyst 3-10 cm)
Frequently diagnosed on prenatal ultrasound
Small CPAMs may present with recurrent infections
56
Alveolar capillary dysplasia (ACD)
Inadequate vascularization of alveolar parenchyma -> reduced number of capillaries in alveolar wall
Pulmonary lobules can be malformed
Pulmonary veins are frequently misaligned
Presents as PPHN early, 10-15% can present at 2-6 weeks of life
Due to failure of fusion of double capillary network
Diffuse disease in 85% of patients
57
Congenital pulmonary lymphangiectasis
Extremely rare, males 2:1
| Dilated pulmonary lymphatics, chylothorax
58
CDH
1:2200-4000 births
85% on left side, 1% bilateral
Posterolateral (Bochdalek, more common) or central (Morgagni) defects in diaphragm
20-60% have multiple anomalies
Frequently have pulmonary hypoplasia and PPHN
Severity related to size of defect, early onset in gestation, presence of liver
59
CDH severity assessment
```
Observed/expected LHR (lung area/head circumference)
- Extreme < 15%
- Severe 15-25%
- Moderate 26-35%
- Mild 36-45%
Lung/chest transverse diameter ratio
Fetal liver in chest
Fetal lung volume by MRI/US
Size of pulmonary artery
```
60
Surfactant
Made up of highly organized lipids and surfactant proteins
Reduces surface tension, regulates surfactant structure/metabolism, enhances host defense
Decrease surface tension: saturated phosphatidylcholine, surfactant proteins B & C
61
Advantages of surfactant
Low surface tension increases compliance and reduces work of breathing
Stabilizes alveoli
Keeps alveoli dry by reducing transudation of fluid
62
Surfactant composition
```
Disaturated phosphatidylcholine (DPPC) = 40%
Monounsaturated PC = 25%
Protein = 10%
Phosphatidylglycerol = 8%
Other = 8%
Neutral fat = 5%
Cholesterol = 4% 
```
63
Surfactant life cycle
Starts in endoplasmic reticulum (ER) of type 2 cell
Goes to Golgi body
Forms a lamellar body and adds proteins/lipids/ABCA3 transporter
Forms tubular myelin
Stretches across surface of alveolus
Then destroyed by alveolar macrophage or recycled
64
Surfactant deficient lungs (RDS)
Stiff lungs = Low compliance
Increased WOB
Atelectasis/low lung volumes
Alveoli filled with transudate 2/2 lack of stretch
Gas diffusion block -> hypoxia and hypercapnia
PPHN
65
Variables that impact distribution of surfactant
```
Gravity
Volume of instillation (larger better)
Speed of instillation (faster better)
Surfactant type
Fluid volume in lung (helps early on, surfactant spreads more quickly/evenly)
```
66
Phosphatidylglycerol test for fetal lung maturity
Appears at 35 weeks
If it is in the amniotic fluid the lungs are mature
Requires thin layer chromatography
67
Lamellar body count for fetal lung maturity
10,000-200,000/mL
>45,000 = mature lungs
Requires infrared spectroscopy
68
Fetal lung maturity testing
High sensitivity for diagnosing maturity (90%)
Lower specificity (60-80%)
Mature -> high PPV
Immature results -> accurate prediction of RDS only 30-50% of time
69
L/S ratio
```
Sphingomyelin: General membrane lipid
Lecithin (phosphatidylcholine)
- <0.5 at 20 wks
- 1 at 32 wks
- 2 at 35 wks
Not good with contaminated specimens
Long turnaround time
```
70
Surfactant protein A
Hydrophilic
Gene on chromosome 10
Involved in tubular myelin and host defense
71
Surfactant protein D
Hydrophilic
Gene on chromosome 10
Involved in surfactant lipid homeostasis, host defense, antioxidant
No human diseases found
72
Surfactant protein B
Hydrophobic
Gene on chromosome 2
Involved in surface tension reduction, tubular myelin, type 2 cell functions
73
Surfactant protein C
Hydrophobic
Gene on chromosome 8
Involved in surface tension reduction, film stability
74
ABCA3 mutations
Autosomal recessive
30-40% of all refractory acute respiratory failure in a newborn
Most severe forms need lung transplant
Less severe forms can respond to steroids
75
SP-B Deficiency
Autosomal recessive
Presents as term RDS
Lethal
No lamellar bodies, no tubular myelin, no surfactant function
No sustained response to exogenous surfactant
Treatment requires lung transplant
76
SP-C Deficiency
```
Autosomal dominant
50% de novo mutations
Chronic lung disease of infancy
RDS, nonspecific interstitial lung disease
Treatment is lung transplant
```
77
Alveolar proteinosis
GM – CSF signaling
78
Dead space
Physiological = anatomic + alveolar
| Calculated by Bohr equation
79
Comparison of lung mechanics (adult vs neonate)
Neonate
- Inc RR
- Inc MV
- Inc alveolar ventilation
- Inc oxygen consumption
Adult
- Inc TV
- Inc total lung capacity
- Inc inspiratory capacity
- Inc Vital capacity
80
Hypoxic pulmonary vasoconstriction
Tries to keep ventilation and perfusion matched
Blood vessels constrict so that blood isn’t going to alveoli that are not ventilated
Normal physiology
81
Pulmonary Vascular resistance and lung volume
PVR is lowest near FRC
Increases at both high and low lung volumes
-> septal capillaries in alveolar walls are stretched -> diameters reduced
82
PPHN due to Maladaptation
Pulmonary structure normal but PVR elevated
- hypoxia
- hypothermia
- hyperviscosity
- pneumonia
- meconium aspiration
- sepsis
83
PPHN from Maldevelopment
Abnormal pulmonary structural development
Smooth muscle hypertrophy
- intrauterine hypoxia, fetal ductal closure
Decreased total pulmonary artery cross-sectional area
- pulmonary hypoplasia (CDH, congenital)
- Alveolar capillary dysplasia
84
PPHN
Usually in term or post-term infants
Single S2
Pre- and post-ductal saturation differential if PDA present due to R ->L shunting
Suspect if hypoxic and failing to respond as expected
- for every 1% increase in FiO2, PaO2 to should increase by 7
HFV plus iNO is better than HFV or iNO alone in severe PPHN
85
Factors affecting diffusion
Diffusion distance
- immature lung
- interstitial edema or emphysema
Area for diffusion
- atelectasis
- pulmonary edema
- immature lung
- new BPD
Partial pressure gradient
- alveolar MV
- PaCO2

86
Factors affecting anatomical dead space
```
ETT size
ETT length
Flow sensor
Suction apparatus
Acquired tracheomegaly
End tidal CO2 detector
```
87
Factors affecting alveolar dead space
Hyperinflation
Heterogenous inflation
Decreased pulmonary blood flow
88
Causes of elevated PaCO2
Decreased tidal volume - decreased lung compliance, increased airway resistance, decreased patient effort
Increased physiologic dead space - added instrument, overinflation
Diffusion block - pulmonary edema
Loss of surface area - atelectasis, alveolar edema
Increased CO2 production - fever, sepsis, cold stress
89
Beneficial effects of acidosis
- increased respiratory drive
- increased release of oxygen
- increased ionized calcium
- dilation of small airways
- improved V/Q matching
- increased sympathetic tone (inc HR, inc contractility)
90
Hypoxemia
Decreased oxygen tension (PaO2)
91
Hypoxia
Decreased oxygen delivery to the tissues
92
Factors that affect mean airway pressure
PEEP (biggest)
PIP
IE ratio
Rise time/flow
93
Right shift on oxyhemoglobin dissociation curve
Decreased oxygen affinity
Increased temperature
Acidosis (inc H, inc pCO2)
Increased 2,3-DPG
94
Left shift on the oxyhemoglobin dissociation curve
Increased oxygen affinity
Decreased temperature
Alkalosis (decreased H and pCO2)
Decreased 2,3-DPG
Fetal hemoglobin
95
Bohr effect
Increased PCO2 leads to more unloading of oxygen from hemoglobin
96
Haldane affect
Deoxygenation of blood increases its ability to carry CO2
97
Type I pneumocytes
```
Shaped like a fried egg
Spread thinly across the alveolar surface (covers 90%)
Fewer number of cells in alveolar lining
Important role in gas exchange
Derived from type II cells
```
98
Type II pneumocytes
Cuboidal shape
Covers 10% of alveolar surface
Greater number of cells in alveolar lining
Important role in surfactant metabolism and secretion
Progender to type I cells
99
Total respiratory system resistance
Chest wall 25%
Airway 55%
Lung tissue 20%
50% of airway resistance is contributed by resistance in the nasal passages
100
How much FLF is actively secreted every day?
250-300 ml/day
101
Average fetal lung volume
20-30 mL
102
What medication inhibits the secretion of fetal lung fluid?
Bumetanide
103
What medications inhibit absorption of FLF?
Na/K-ATPase inhibited by Ouabain
| ENaC inhibited by amiloride
104
FLF clearance prior to labor
35% cleared during days prior to birth
- decreased secretion via decreased Cl secretion
- increased Na transport from alveolar space (ENaC)
- increased lymphatic oncotic pressure
105
FLF clearance during labor
30% cleared
- ENaC - active Na reabsorption
- hormones increase Na uptake (epinephrine, glucocorticoids, vasopressin, aldosterone)
106
How much FRC is established in the first hour after birth?
80-90%
107
Early stages of lung development
Embryologic and pseudoglandular
| Branching morphogenesis occurs
108
Middle stages of lung development
Canalicular and saccular
- terminal unit capable of gas exchange
- type 2 -> type 1 cell differentiation
- capillary bed formation
109
Mutations on FGFR2
Pfeiffer, Apert, Crouzon (laryngomalacia, tracheomalacia, lobar atresia, pulmonary aplasia)
110
Angiogenesis during lung development
Proximal development, new blood vessels from previous ones
111
Vasculogenesis during lung development
Distal vessels form from blood lakes in mesenchyme
| Linked with angiogenesis during pseudoglandular phase
112
Stimulation of alveolarization
Vitamin A
| Thyroxine (T4)
113
What is tracheoesophageal fistula associated with?
VACTERL
| Esophageal atresia
114
What is the most common type of TEF?
EA with distal TEF
115
Pulmonary agenesis
Embryonic phase - lung bud fails to partition
Complete absence of one or both lungs including bronchi, bronchioles, and vasculature (if unilateral has hyperplasia of contralateral lung, no clinical consequences)
116
Primary congenital pulmonary lymphangiectasis
Fatal, a/w Noonan, Ulrich-Turner, T21
- Present with RDS and pleural effusions
- failure of normal regression of lymphatic channels in fetal lung (20 wk)
- Hemihypertrophy and lymphedema may be present
117
Secondary congenital pulmonary lymphangiectasis
Associated with CDH
- HLHS, Cor triatriatum
- thoracic duct agenesis
- TORCH infections
118
Fetal lung testing specimens
Most tests are affected by quality of the amniotic fluid specimen
Ideal is from amniocentesis
Vaginal pool specimens after ROM can be unreliable
119
ABCA3
ATP – binding cassette transporter A3 (ABCA3)
Type 2 cells
Critical for formation of lamellar bodies and surfactant function
120
Anatomical dead space
Gas in the conducting areas of the respiratory system, air does not come into contact with the alveoli
121
Alveolar dead space
Air contacting alveoli without blood flow in their adjacent pulmonary capillaries
Ventilation without perfusion
122
Echo findings in PPHN
```
Structurally normal heart
R->L shunting
Flattening or bowing of the IVS
Tricuspid regurg
Must see all 4 pulmonary veins to rule out TAPVR
```
123
Negative effects of acidosis
- increased PVR
- cerebral vasodilation
- increased intracranial pressure
- decreased cardiac output
- hyperkalemia
- altered cellular energy and enzyme functions
124
Exudative effusion
pH <7.4
WBC >1000
LDH >200
125
Transudative effusion
pH >7.4
WBC <1000
LDH <200
Chylothorax fluid - classically appears milky with >80% lymphocytes, elevated triglycerides, xanthochromia
126
Is CPAM connected to tracheobronchial tree?
Yes
127
Blood supply for CPAM?
Pulmonary vessels
128
Location preference for CPAM
Slight predilection for lower lobes
| R = L
129
Ouobain
Inhibits Na/K-ATPase, decreased FLF absorption
130
Amiloride
Inhibits ENaC channels
131
Which surfactant protein is most abundant?
SP- A
132
What happens if you knock out FGF10 during lung development?
Complete agenesis of lungs with only trachea visible
133
Alveoli present at birth
50-150 million
134
Composition of fetal lung lymph and plasma
Lower Chloride 107
Higher pH 7.31
Higher protein 3.27
(Than fetal lung fluid)
135
Effect of antenatal corticosteroids on fetal lung fluid
Increases absorption of FLF
| Increased expression and activity of ENaC channels
136
Lung:body weight ratio for lung hypoplasia
- <0.015 <28 weeks
| - <0.012 >28 weeks
137
Lung DNA content for lung hypoplasia
<100 mg/kg body weight
138
Lung weight (for lung hypoplasia)
- <1kg = 15g/kg
| - >1kg = 12g/kg
