1
Q
what is respiratory tract derived from
A
endoderm
lung from the ventral bud of the esophagus that arises from the foregut
2
Q
pulmonary vasculature forms from what branch of the aortic arch
A
6th
3
Q
when are pre-acinar arteries development complete
A
16 weeks
4
Q
when does intraacinar arteries complete development
A
8-10 years
5
Q
vascular wall thickness:total vascular diameter in fetus
A
> than adults; remains constant in second half of gestation
6
Q
what enhances alveolarization
A
vit A
thyroxine
7
Q
what delays alveolarization
A
postnatal steroids
supplemental oxygen
nutritional deficiencies
mechanical ventilation
insulin
inflammation
8
Q
stages and timing of pulmonary development
A
embryonic (0-5 weeks)
pseudoglandular (5-16 weeks)
canalicular (16-25 weeks)
saccular (25-36 weeks
alveolar (36 +)
9
Q
what happens in embryonic stage of pulmonary development
A
lung from ventral bud of esophagus
evidence of 5 lobes
elongation of proximal airway
pulmonary vascular development (6th aortic arch)
10
Q
what happens in pseudoglandular stage of pulmonary development
A
- branching up to terminal bronchi
- start making AF
- pneumocyte precursors
- vasculature of arteries and veins
- separation of thoracic and peritoneal cavity (7)
11
Q
what happens in canalicular stage of pulmonary development
A
- canaliculi branching
- preliminary gas exchange
- type 2 into type 1 pneumocytes
- lung becomes viable
12
Q
what happens in saccular stage of pulmonary development
A
terminal sacs form - last generation of air spaces
gas exchange alveolar-capillary membrane
13
Q
what happens in alveolar stage of pulmonary development
A
alveoli increase in diameter
microvascular growth and vessel maturation
14
Q
disorders of embryonic stage
A
laryngeal cleft
tracheal stenosis
TEF
bronchogenic cyst
15
Q
disorders of pseudoglandular stage
A
abnormal branching
CDH
congenital lobar emphysema
CPAM
pulmonary lymphangiectasia
16
Q
disorders of canalicular stage
A
pulmonary hypoplasia
surfactant deficiency
ACD
17
Q
disorders of saccular stage
A
pulmonary hypoplasia
surfactant deficiency
18
Q
disorders of alveolar stage
A
surfactant deficiency
congenital lobar emphysema
pulmonary hypertension
19
Q
which arteries have muscle?
A
pre-acinar not intra-acinar
20
Q
type 1 vs type 2 pneumocytes
A
shape:
1. fried egg/tight junctions
2. cuboid
percentage of surface
1. 90%
2. 10%
more cells: 2
role in gas exchange: 1
surfactant: 2
21
Q
what percent of FLF is cleared prenatally, during active labor, and postnatally
A
35 - 30 -35%
22
Q
prenatal clearance
A
- decreased formation
- Cl secretion decreases & Na into cell increases - FLF follows
- increased lymphatic oncotic pressure promoting alveoli –> lymphatics
23
Q
active labor clearance
A
- mechanical compression
- catecholamines –> increase Na transport into cells
- cortisol and thyroid –> increase Na transport into cells
24
Q
postnatal clearance
A
- lung distension pressure –> fluid into interstitium
- lymphatic transition
25
components of surfactant
50% phosphatidylcholine disaturated
20% phosphatidylcholine monosaturated
8% SP A, B, C, D
8% neutral lipids
8% phosphatidyl glyerol
6% other
26
which surfactant proteins are excreted by type II and clara cells and which by type II alone?
both = A and B
only type II = C and D
27
what chromosomes express each surfactant protein
A = 10
B = 2
C = 8
D = 10
28
when in gestation is each surfactant protein expressed
A =early third
B= end of first
C = end of first
D = latest in third
29
which surfactant protein is most abundant
SP A
30
which surfactant proteins are hydrophillic and which are hydrophobic?
hydrophillic = A and D (both collectins)
hydrophobic = B and C
31
which surfactant proteins are induced by steroids
A, B, and C
32
what does SP A do?
tubular myelin formation
phospholipid uptake and inhibits its secretion
host defense: opsonization, inflammation modulation
*helps regulate the expression and uptake of surfactant*
33
what does SP B do?
SURFACTANT FUNCTION
tubular myelin formation
surface absorption of phospholipids
34
what does SP C do?
SURFACTANT FUNCTION
surface absorption of phospholipids
35
what does SP D do?
- host defense:
-- opsonization
-- inflammation modulation
-- antioxidant
- surfactant lipid homeostasis
- regulates reuptake and recycling
36
ABCA3 pathophys
AR
transport of lipids --> lack of DPPC and PG --> decreased lamellar bodies
37
Surfactant metabolism
1. transport
2. lamellar storage
3. secretion
4. adsorption
5. turnover
6. recycling
7. clearance
38
which pregnancy related factors delay lung development?
diabetes
rh immunization
2nd born twin
male
c-sec
prematurity
insulin
tgf beta
androgen
39
phosphatidylinositol change over time
peaks around 35 then drops
present before phosphotidylglycerol
40
sphingomyelin change over time
does NOT reflect lung maturity
decreases after 32 weeks
41
what is ratio that is used to reflect lung maturity?
lecithin/sphingomyelin
42
lecithin change over time
increases with GA
reflects lung maturity
> 2 = mature; 2 at 35 weeks
43
phosphatidylglycerol change over time
increases last; after 34-35 weeks
not necessary for surfactant function
reflects lung maturity
44
what is foam stability or shake test
if AF mixed with ethanol forms foam then phosphatidyl glycerol is present suggesting mature lung
high false negative
45
what is lamellar body solubilization test
detects unraveling or solubilization of lamellar bodies in amniotic fluid if mature lung tissue
46
laplace law
**P = 2T/r**
P = pressure to resist alveolar collapse
T = surface tension
r - alverolar radius
47
boyles law
P1V1 = P2V2
48
what is the hering breuer inflation reflex
lung overinflation --> inspiration stops as pulmonary stretch receptors in smooth muscle send signals to afferent neural input in medulla causing vagal nerve to inhibit inspiration
49
what zone does neonatal lung mimic?
zone 3
Pa > Pv > PA
50
what zone does air trapping or alveolar distension cause neonatal lung to mimic?
zone 1 or 2 leading to decreased pulmonary venous compression and decreased pulmonary blood flow
51
what zone does extravascular fluid cause neonatal lung to mimic?
zone 4 with increase PVR and decreased pulmonary ventilation and alveolar collapse
52
physiologic dead space =
(arterial CO2 - Expired CO2)/arterial CO2 X TV
53
resistance =
change P/change flow
54
% shunt =
(O2 content pulm capillary - O2 content systemic artery)/
(O2 content pulm capillary - O2 content mixed venous)
55
total respiratory system resistance components
25% chest wall
55% airway
20% lung tissue
usually: 40-55 cm H20/L/s
56
airway system resistance components
* 50% nasal
* rest first few generation of bronchi
* distal contribute very little
57
poiseulles law for laminar flow
flow =
(change P x pi x r^4)/(8 x length x viscosity)
58
compliance =
change V/change P
59
elastance =
change P / change V
60
work of breathing =
P x V
61
Power =
work x force
62
time constant =
resistance x compliance
63
one time constants =
time for alveoli to discharge 63%
64
two time constants =
alveoli discharges 86%
65
three time constants
alveoli discharges 95%
66
which respiratory mechanics increase in neonates
RR
residual volume
MV
alveolar ventilation = TV - deadspace x RR
chest wall compliance
lung tissue resistance
oxygen consumption
67
which respiratory mechanics decrease in neonates
TV
TLC
IC
VC
time constant
lung compliance - neonates stiffer lungs
muscle strength and endurance
68
which respiratory mechanics are same in neonates and adults
dead space
FRC
69
normal PaO2 and normal O2 sat
decreased O2 content
severe anemia
70
decreased PaO2, decreased O2 saturation, decreased O2 content
severe V/Q mismatch
high altitude
71
normal paO2, decreased O2 saturation and content
CO poisoning
72
O2 content =
O2 bound to Hb + dissolved O2
{1.34 x Hb X O2 sat} + {0.003 x paO2}
73
what does O2 saturation represent
percentage of heme binding sites that are saturated with O2
74
A-a gradient =
pAO2 - paO2 =
[FiO2 x (Pb - pH20)] - {paCO2 / R} - paO2
Pb = 760
pH20 = 47
R = 0.8
75
oxygen delivery =
CO x O2 content =
CO x (O2 bound to Hb + dissolved O2)
76
fick principle for O2 consumption
O2 delivered to tissue - O2 returning to heart
= blood flow x O2 arterial - blood flow x O2 venous
= blood flow (O2 artery - O2 venous)
= CO x [Hb] x 1.34 (O2 artery - O2 venous)
77
increased oxygen consumption in:
1. increased caloric intake
2. decreased temp
3. neonate > adult
4. term > preterm
5. AGA > SGA
78
shift right oxy Hb curve
acidosis
higher paCO2
increased adult Hb
increased temp
increased 2,3 DPG
79
bohr vs haldane
**bohr** = changes in **O2** **bound** to Hb based on pCO2
**haldane**= change in **CO2** **bound** to Hb based on amount O2
80
oxygenation index =
(MAP x FiO2)/postductal paO2 x 100
81
increase in flow does what to PIP?
get to PIP faster
82
theories on how gas transport works in HFOV
* **bulk convection** - bulk axial gas flow
* **pendelluft** - gas moving between neighboring alveoli due to different time constants
* **asymmetric velocity**
* **taylor dispersion** - parabolic movement - increased area for diffusion
* **molecular diffusion**- transport of gases across alveoli
83
differences in HFOV and HJV
1. **expiration type** :
HFOV - active expiration (less gas trapping)
HJV = passive
2. **inspiration time** : HFOV
3. **expiration time** : HJV
4. **frequency**
HJV 4-11; HFOV 3-15
5. **fixed** inspiratory time HFOV **adjustable** with HJV
6. **sigh breaths** with HJV not HFOV
7. **TV** independent of frequency with HJV not HFOV
84
early pneumonia causes
GBS
E coli
klebsiella
listeria
85
late pneumonia causes
s.aureus
pseudomonas
fungal
chlamydia
86
how do supraglottic, laryngeal and intrathoracic obstructions change with inspiration/expiration?
supraglottic - worsens with inspiration
laryngeal - fixed so no change
intrathoracic - worsens with expiration
87
types of complete vascular rings
1. double aortic arch (40%) from right and left 4th branchial arch
2. right AoA with ligamentous arteriosum/PDA (30%) - persistence of right 4th branchial arch
88
types of incomplete vascular ring
1. aberrant right subclavian artery (20%); rSCA from descending aorta
2. anomalous origin of the innominate artery (10%)
3. aberrant LPA (rare)
89
MC locations of chylothorax
R > L > bilateral
90
why MCT for chylothorax?
bypasses lymphatic system
91
how does octreotide work for chylothorax?
mild vasoconstriction of splanchnics???
92
location of congenital lobar emphysema
LUL 45%
RML 30%
RUL 20%
93
CPAM vs BPS
tracheobronchial communication
CPAM = yes
BPS = no
94
CPAM vs BPS
blood supply
CPAM = pulmonary circulation
BPS = anomolous systemic vessels - ie aorta
95
epi of types of CPAM
0 rare
1 MCC 50-70%
2 20-40%
3 10%
4 rare
96
which CPAM has most associated anomalies
type 2
97
timing of defects by type of CPAM
0 early
1 7-10wk
2 3rd wk
3 26-28d
4 ??
98
size and location of cysts by CPAM type
0 very small, all lobes (upper tracheobronchial tree)
1 large, usually just 1
2 multiple small
3 very large microcystic entire lobe or multiple lobes
4 large
99
which types of CPAM have mass effect
type 1 3 and 4
100
cell types in CPAM?
Which have mucus cells?
0 and 1 ciliated pseudostratified
2 ciliated cuboid
3 nonciliated cuboid
4 nonciliated flattened
mucus cells in type 0 and 1 only
101
prognosis by type of CPAM
excellent 1 and 4 - excision is curative
poor 0 and 2 for associated anomalies
poor 3 because of pulmonary hypoplasia
102
bronchogenic cyst pathophys
anomalous budding of foregut leading to cystic mass that communicates with airway
central or peripheral
may be posterior to trachea
103
congenital pulmonary lymphangiectasia types
primary (tri 21, noonan, turner)
secondary (HLHS, thoracic duct agenesis, intrauterine infection)
failure of lymphatic vessel regression at 20 weeks or lymphatic obstruction
poor prognosis
104
bronchopulmonary sequestration pathophys
nonfunctioning lung tissue without communication with tracheobronchial tree
105
types of BPS
intralobar 75% (lower > upper, L > R); 10-20% risk anomalies
extralobar 25% (L>R often between LLL and diaphragm); 40-60% risk of anomalies
106
alveolar capillary dysplasia pathophys
inadequate vascularization of alveoli with decreased number of capillaries adjacent to alveoli
malaligned pulmonary veins
107
MoA acetazolamide
carbonic anhydrase inhibitor
inhibits NaHCO3 reabsorption
acts on proximal tubule
108
MoA furosemide/bumetanide
blocks active Cl transport
ascending loop of henle
109
MoA chlorothiazide
inhibits NaCl reabsorption
acts on distal tubule
inhibits pancreatic release of insulin; risk of hyperglycemia
110
MoA spironolactone
antagonist of aldosterone
acts on collecting duct
K sparing
111
Surfactant Metabolism
1. transport SP B and SPC into multivesicular bodies
2. lamellar storage
3. secretion into alveolar sub space and interact with SP-A to form tubular myelin reservoir
4. adsorption + film creation to reduce tension
5. turnover by endocytosis by alveolar type II cells
6. recycling into multivesicular and lamellar bodies
7. alveolar macrophages clear and catabolize surfactant remnants
112
what percent of secreted surfactant is recycled?
95%
113
how long does surfactant turnover take?
10 hours
114
teratogenic agents associated with CDH
mycophenolate mofetil, allopurinol, and lithium
115
syndromes associated with CDH
Fryns
Denys Drash
Cornelia de Lange
Marfan
spondylocostal dysostosis
craniofrontonasal syndrome
116
ventilation equations for conventional and HFV
Conventional ventilation: Q ∝ f × VT
HFV (jet and oscillatory): Q ∝ f × (VT)2
117
Episodic interruption of fetal breathing mediator
Prostaglandin
118
hallmark of "new" BPD
disruption of normal alveolar and vascular development with subsequent diffuse alveolar and capillary hypoplasia
119
SP B deficiency associated with what genetic mutation
121ins2 SFTB gene chr 2
N. Euro
120
MoA caffeine
- stimulation **medullary** respiratory center
- increased sensitivity to **CO2**
- diaphragmatic contractility
- antagonism **adenonsine 1+2 R** in brain > inhibit **phosphodiesterase** > increase **cAMP** and intracellular Ca release
- upregulates **GABA-R**
121
antiinflammatory effect of glucocorticoids mediator
**annexin A1**
- decreased **phospholipid A2**--> decreased PG, thromboxane, PC, leukotrienes
- suppression **COX1/2**
- regulation of surfactant production
- **antioxidant** production
- enhanced **adrenergic** activity
