Pulmonary Flashcards
what is respiratory tract derived from
endoderm
lung from the ventral bud of the esophagus that arises from the foregut
pulmonary vasculature forms from what branch of the aortic arch
6th
when are pre-acinar arteries development complete
16 weeks
when does intraacinar arteries complete development
8-10 years
vascular wall thickness:total vascular diameter in fetus
> than adults; remains constant in second half of gestation
what enhances alveolarization
vit A
thyroxine
what delays alveolarization
postnatal steroids
supplemental oxygen
nutritional deficiencies
mechanical ventilation
insulin
inflammation
stages and timing of pulmonary development
embryonic (0-5 weeks)
pseudoglandular (5-16 weeks)
canalicular (16-25 weeks)
saccular (25-36 weeks
alveolar (36 +)
what happens in embryonic stage of pulmonary development
lung from ventral bud of esophagus
evidence of 5 lobes
elongation of proximal airway
pulmonary vascular development (6th aortic arch)
what happens in pseudoglandular stage of pulmonary development
- branching up to terminal bronchi
- start making AF
- pneumocyte precursors
- vasculature of arteries and veins
- separation of thoracic and peritoneal cavity (7)
what happens in canalicular stage of pulmonary development
- canaliculi branching
- preliminary gas exchange
- type 2 into type 1 pneumocytes
- lung becomes viable
what happens in saccular stage of pulmonary development
terminal sacs form - last generation of air spaces
gas exchange alveolar-capillary membrane
what happens in alveolar stage of pulmonary development
alveoli increase in diameter
microvascular growth and vessel maturation
disorders of embryonic stage
laryngeal cleft
tracheal stenosis
TEF
bronchogenic cyst
disorders of pseudoglandular stage
abnormal branching
CDH
congenital lobar emphysema
CPAM
pulmonary lymphangiectasia
disorders of canalicular stage
pulmonary hypoplasia
surfactant deficiency
ACD
disorders of saccular stage
pulmonary hypoplasia
surfactant deficiency
disorders of alveolar stage
surfactant deficiency
congenital lobar emphysema
pulmonary hypertension
which arteries have muscle?
pre-acinar not intra-acinar
type 1 vs type 2 pneumocytes
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
what percent of FLF is cleared prenatally, during active labor, and postnatally
35 - 30 -35%
prenatal clearance
- decreased formation
- Cl secretion decreases & Na into cell increases - FLF follows
- increased lymphatic oncotic pressure promoting alveoli –> lymphatics
active labor clearance
- mechanical compression
- catecholamines –> increase Na transport into cells
- cortisol and thyroid –> increase Na transport into cells
postnatal clearance
- lung distension pressure –> fluid into interstitium
- lymphatic transition
components of surfactant
50% phosphatidylcholine disaturated
20% phosphatidylcholine monosaturated
8% SP A, B, C, D
8% neutral lipids
8% phosphatidyl glyerol
6% other
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
what chromosomes express each surfactant protein
A = 10
B = 2
C = 8
D = 10
when in gestation is each surfactant protein expressed
A =early third
B= end of first
C = end of first
D = latest in third
which surfactant protein is most abundant
SP A
which surfactant proteins are hydrophillic and which are hydrophobic?
hydrophillic = A and D (both collectins)
hydrophobic = B and C
which surfactant proteins are induced by steroids
A, B, and C
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
what does SP B do?
SURFACTANT FUNCTION
tubular myelin formation
surface absorption of phospholipids
what does SP C do?
SURFACTANT FUNCTION
surface absorption of phospholipids
what does SP D do?
- host defense:
– opsonization
– inflammation modulation
– antioxidant - surfactant lipid homeostasis
- regulates reuptake and recycling
ABCA3 pathophys
AR
transport of lipids –> lack of DPPC and PG –> decreased lamellar bodies
Surfactant metabolism
- transport
- lamellar storage
- secretion
- adsorption
- turnover
- recycling
- clearance
which pregnancy related factors delay lung development?
diabetes
rh immunization
2nd born twin
male
c-sec
prematurity
insulin
tgf beta
androgen
phosphatidylinositol change over time
peaks around 35 then drops
present before phosphotidylglycerol
sphingomyelin change over time
does NOT reflect lung maturity
decreases after 32 weeks
what is ratio that is used to reflect lung maturity?
lecithin/sphingomyelin
lecithin change over time
increases with GA
reflects lung maturity
> 2 = mature; 2 at 35 weeks
phosphatidylglycerol change over time
increases last; after 34-35 weeks
not necessary for surfactant function
reflects lung maturity
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
what is lamellar body solubilization test
detects unraveling or solubilization of lamellar bodies in amniotic fluid if mature lung tissue
laplace law
P = 2T/r
P = pressure to resist alveolar collapse
T = surface tension
r - alverolar radius
boyles law
P1V1 = P2V2
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
what zone does neonatal lung mimic?
zone 3
Pa > Pv > PA
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
what zone does extravascular fluid cause neonatal lung to mimic?
zone 4 with increase PVR and decreased pulmonary ventilation and alveolar collapse
physiologic dead space =
(arterial CO2 - Expired CO2)/arterial CO2 X TV
resistance =
change P/change flow
% shunt =
(O2 content pulm capillary - O2 content systemic artery)/
(O2 content pulm capillary - O2 content mixed venous)
total respiratory system resistance components
25% chest wall
55% airway
20% lung tissue
usually: 40-55 cm H20/L/s
airway system resistance components
- 50% nasal
- rest first few generation of bronchi
- distal contribute very little
poiseulles law for laminar flow
flow =
(change P x pi x r^4)/(8 x length x viscosity)
compliance =
change V/change P
elastance =
change P / change V
work of breathing =
P x V
Power =
work x force
time constant =
resistance x compliance
one time constants =
time for alveoli to discharge 63%
two time constants =
alveoli discharges 86%
three time constants
alveoli discharges 95%
which respiratory mechanics increase in neonates
RR
residual volume
MV
alveolar ventilation = TV - deadspace x RR
chest wall compliance
lung tissue resistance
oxygen consumption
which respiratory mechanics decrease in neonates
TV
TLC
IC
VC
time constant
lung compliance - neonates stiffer lungs
muscle strength and endurance
which respiratory mechanics are same in neonates and adults
dead space
FRC
normal PaO2 and normal O2 sat
decreased O2 content
severe anemia
decreased PaO2, decreased O2 saturation, decreased O2 content
severe V/Q mismatch
high altitude
normal paO2, decreased O2 saturation and content
CO poisoning
O2 content =
O2 bound to Hb + dissolved O2
{1.34 x Hb X O2 sat} + {0.003 x paO2}
what does O2 saturation represent
percentage of heme binding sites that are saturated with O2
A-a gradient =
pAO2 - paO2 =
[FiO2 x (Pb - pH20)] - {paCO2 / R} - paO2
Pb = 760
pH20 = 47
R = 0.8
oxygen delivery =
CO x O2 content =
CO x (O2 bound to Hb + dissolved O2)
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)
increased oxygen consumption in:
- increased caloric intake
- decreased temp
- neonate > adult
- term > preterm
- AGA > SGA
shift right oxy Hb curve
acidosis
higher paCO2
increased adult Hb
increased temp
increased 2,3 DPG
bohr vs haldane
bohr = changes in O2 bound to Hb based on pCO2
haldane= change in CO2 bound to Hb based on amount O2
oxygenation index =
(MAP x FiO2)/postductal paO2 x 100
increase in flow does what to PIP?
get to PIP faster
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
differences in HFOV and HJV
-
expiration type :
HFOV - active expiration (less gas trapping)
HJV = passive - inspiration time : HFOV
- expiration time : HJV
-
frequency
HJV 4-11; HFOV 3-15 - fixed inspiratory time HFOV adjustable with HJV
- sigh breaths with HJV not HFOV
- TV independent of frequency with HJV not HFOV
early pneumonia causes
GBS
E coli
klebsiella
listeria
late pneumonia causes
s.aureus
pseudomonas
fungal
chlamydia
how do supraglottic, laryngeal and intrathoracic obstructions change with inspiration/expiration?
supraglottic - worsens with inspiration
laryngeal - fixed so no change
intrathoracic - worsens with expiration
types of complete vascular rings
- double aortic arch (40%) from right and left 4th branchial arch
- right AoA with ligamentous arteriosum/PDA (30%) - persistence of right 4th branchial arch
types of incomplete vascular ring
- aberrant right subclavian artery (20%); rSCA from descending aorta
- anomalous origin of the innominate artery (10%)
- aberrant LPA (rare)
MC locations of chylothorax
R > L > bilateral
why MCT for chylothorax?
bypasses lymphatic system
how does octreotide work for chylothorax?
mild vasoconstriction of splanchnics???
location of congenital lobar emphysema
LUL 45%
RML 30%
RUL 20%
CPAM vs BPS
tracheobronchial communication
CPAM = yes
BPS = no
CPAM vs BPS
blood supply
CPAM = pulmonary circulation
BPS = anomolous systemic vessels - ie aorta
epi of types of CPAM
0 rare
1 MCC 50-70%
2 20-40%
3 10%
4 rare
which CPAM has most associated anomalies
type 2
timing of defects by type of CPAM
0 early
1 7-10wk
2 3rd wk
3 26-28d
4 ??
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
which types of CPAM have mass effect
type 1 3 and 4
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
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
bronchogenic cyst pathophys
anomalous budding of foregut leading to cystic mass that communicates with airway
central or peripheral
may be posterior to trachea
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
bronchopulmonary sequestration pathophys
nonfunctioning lung tissue without communication with tracheobronchial tree
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
alveolar capillary dysplasia pathophys
inadequate vascularization of alveoli with decreased number of capillaries adjacent to alveoli
malaligned pulmonary veins
MoA acetazolamide
carbonic anhydrase inhibitor
inhibits NaHCO3 reabsorption
acts on proximal tubule
MoA furosemide/bumetanide
blocks active Cl transport
ascending loop of henle
MoA chlorothiazide
inhibits NaCl reabsorption
acts on distal tubule
inhibits pancreatic release of insulin; risk of hyperglycemia
MoA spironolactone
antagonist of aldosterone
acts on collecting duct
K sparing
Surfactant Metabolism
- transport SP B and SPC into multivesicular bodies
- lamellar storage
- secretion into alveolar sub space and interact with SP-A to form tubular myelin reservoir
- adsorption + film creation to reduce tension
- turnover by endocytosis by alveolar type II cells
- recycling into multivesicular and lamellar bodies
- alveolar macrophages clear and catabolize surfactant remnants
what percent of secreted surfactant is recycled?
95%
how long does surfactant turnover take?
10 hours
teratogenic agents associated with CDH
mycophenolate mofetil, allopurinol, and lithium
syndromes associated with CDH
Fryns
Denys Drash
Cornelia de Lange
Marfan
spondylocostal dysostosis
craniofrontonasal syndrome
ventilation equations for conventional and HFV
Conventional ventilation: Q ∝ f × VT
HFV (jet and oscillatory): Q ∝ f × (VT)2
Episodic interruption of fetal breathing mediator
Prostaglandin
hallmark of “new” BPD
disruption of normal alveolar and vascular development with subsequent diffuse alveolar and capillary hypoplasia
SP B deficiency associated with what genetic mutation
121ins2 SFTB gene chr 2
N. Euro
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
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
