Respiratory Day Flashcards
from Pediatrix review
ENaC is inhibited by what
Amiloride
Fetal lung fluid and aminoic fluid
lung fluid go to aminoic fluid but amnioci fluid don’t go to lung (small)
amount of FLF secreted daily
250-300ml/day in human (4-5ml/kg/hr in near term infants)
20-30ml/kg, similar to FRC.
pressure gradient 3-5 cm H2O across laryn. –> CPAP volume.
secretion FLF:
inhibit by what
Driven by what molecule
inhibit by: Bumetanide, beta adrenergics, vaspressin, epinephrine
Na-K-2Cl Tri-transporter and Chloride
channels (ClC2, CLCN2)
Cl
absorption of FLF by what channel
Driven by what molecule
inhibited by what medications?
Epithelial Na Channel (ENaC) (face alveolar lumen)
Na-K-ATPase (face blood)
Na
Inhibited by Amiloride.
Na-K-ATPase inhibited by Ouabain
FLF composition
rich in Na
rich in Cl
protein content is ZERO –> allow the fluid to be absorbed after birth
low bicarb
very acidic
FLF Clearance
Before Birth
During Labor
After Birth
35% cleared during days prior to birth (decrease secretion of FLF through decrease Cl secretion, increase Na transport from alveolar space, increase lymhatic oncotic pressure)
30% cleared during labor:
- ENac Channel, active Na absorption
From catecholamine surge, higher cortisol and thyroid hormone
- mechanical force compresse fetal chest
- epinephrine suppress FLF secretion (cl channels)
35% cleared postnatally: lung distention (↑transpulmonary pressure), ↑ Lymphatic oncotic pressure associated with low fetal alveolar protein, crying.
Fetal Breathing Movement
( not a good card)
occurs in discrete episode (resemble REM sleep in periods of low voltage crotical activity)
principle musles: diaphgragm and glottis.
later half of gestation 40-50% FBM alternates with complete apnea.
without breathing movement, lung cannot grow.
REM sleep in baby
(not a good card)
irregular breathing
loss of upper airway and intercostal muscle activity, leading to a greater risk of airway obstruction
what causes bradycardia after birth
(Maybe not a good card)
lack of pulmonary stretch
Asphyxia -> hypoxia -> carotid chemo-rectorps -> bradycardia.
In addition:
Periglottic stimulation -> laryngeal reflex (tickle vocal cord with suctioning, vocal cord close)
Lung inflation and vagal tone
lung inflation, -> decrease vagal tone -> increase heart rate
What are these respiratory reflexes:
Hering-Breur inflation Reflex
Parodoxical reflex of head
Hering-Breuer Deflation Relex
J receptor reflex ?
Hering Breur Reflex: Lung over-inflation leads to cessation of inspiration. Protective. increase with GA, strongest in first few months. NB>Adults (via pulmonary stretch receptor (on airway smooth muscle > medulla > vagal nerve )
Parodoxical reflex of Head
* Inhibition of Hering Breur reflex results in extended inspiration. initial NB breaths in term infant (parodoxical increase in diaphgramatic contraction during inflation)
* probably important in causing periodic deep sighs breath.
Hering-Breuer Deflation Relex:
increase in ventilatory rate with abrupt deflation of the lungs (i.e. pneumothorax)
associated with deep sign breath.
Help maintain FRC in infant’s
J Receptor Reflex: Juxta capillary receptors; Rapid shallow breathing (can be dissociated from chemoreceptor)
iNO
where does it come from and how does it work?
Arginine becomes NO (nitric oxide, using NO synthase)
iNO convert GTP -> cGMP (guanyl cyclase)
cGMP -> K+ channels -> vasodilation
Sildenafil block PDE5, whcih break down cGMP.
PDE5 = phosphodiesterase 5
what’s most rapidly depleted in neuronal injury and cell death.
Phosphocreatine most rapidly depleted
apoptotic cell death
vs.
necrotic cell death
caspases (in apototic cell death)
Cytochrome c released from mitochondria
activates caspase-8 & caspase-9
Initial hypoxia and glucose deprivation disrupts cellular
homeostasis and ATP depletion
* Loss of Na-K-ATPase, membrane depolarization, influx
of Na, Ca, and H2O
* Excess extracellular glutamate increases Ca entry
* Phospholipases, Xanthine oxidase, nNOS
* Cell swelling and death
what are some of scavengers (or lack of scanvengers) in oxidative stress
(might not be important?)
Lack of scavengers:
glutathione, SOD, catalase,
cholesterol
Radicals with unpaired electrons react with proteins, lipids and DNA producing oxidative damage
inflammatory damage from chorioamnionitis is due to what chemicals
release of cytokines like IL-6, IL-8, interferon gamma as well
(cause iNO production, vasodilation, capillary leak)
Temporal relationship to CP
Prolonged intrauterine hypoxia shows up as what in the cord gas
profound metabolic acidosis
BE high.
what stage in lung development is consider viable
canalicular
primitive alveoli = respiraotry bronchioles
lung buds is from what germ layer
endoderm
pulmonary arteries originated from what?
Pulmonary vein originated from what
6th pair of aortic arches
(also where PDA comes from, the 6th left arch, same as L pulmonary artery)
left atrium
Airway development under control of what signaling
Airway development under control by retinoic acid signaling
In pseudoglandular phase, what gene/signaling pathway control development
*Early branching is regulated by the insulin-like growth factor
*Cellular differentiation (ciliated, goblet, basal) under the control of FGF-10 and FGF-7
*Disruption of FGF-10 results in lung agenesis
*Excess FGF-7 leads to poor differentiation, resembles CPAM
*Mutations on FGFR2 –Pfeiffer, Apert, Crouzons – variety of defects (laryngomalacia, tracheomalacia, lobar atresia, pulmonary aplasia)
*Note: *FGFR3 = achondroplasia
what disease happened during Embryogenic stage of lung development
TEF
tracheal stenosis
laryngeal cleft
Bronchiogenic cyst
what disease happened during Pseudoglandular stage of lung development
CDH (7 weeks)
Congenital lobar emphysema (air trapping, mimic pneumothorax)
Bronchiogenic Cyst ?
Bronchopulmonary sequestration.
Pulmoanry Lymphangiectasia
CPAM (MOST COMMON CONGENITAL LUNG LESION, may. be reduced with steroid. may regress after 25 weeks, Cystic or adenomatous tissue lined with ciliated pseudostratified epithelium)
Scimitar syndrome (R pulmonary vein drains to IVC)
What disease happened during Canalicular stage of lung development
pulmonary hypoplasia
surfactant deficiency
alveolar capillary dysplasia
(FOXF 1 gene)
When does primary septa happen?
Saccular stage:
- terminal sacs / primitive alveoli form.
- sacs are separated from each other by primary septa (start of alveolarization)
Type I and Type II pneumocytes lines the wall.
what stage in lung development does double-capillary network first start to develop
Saccular stage:
walls between the sacs contain double capillary network
Congenital Pulmonary lymphangiectasis
*Extremely rare, males 2:1
*Dilated pulmonary lymphatics, chylothorax
*Associated with Noonan, Ulrich-Turner and Downs
*Primary – fatal , associated with syndromes
- Present with RDS and pleural effusions
- Hemihypertrophy and lymphedema may be present
*Secondary – associated with CHD
- HLHS, Cor Triatum
- Thoracic Duct Agenesis
- Infections (TORCH)
when does secondary septae form
alveolar stage
terminal sacs are separated by secondary septae (adult alveoli).
new double-capillary layers form –> remodeling to form mature single layer (blood-air barrier)
Surfactant’s predominant lipid
(also most abundant proportion of component)
DPPC:
disaturated phosphatidylcholine
what are the principle proteins in surfactant?
what about the rest of them?
SP-B and SP-C are the principle proteins
Hydrophobic.
SP-A and SP-D: these are hydrophilic. NO known human mutations.
A: tubular myelin formation and host defense
D: surface lipid homeostatis, host denfense, anti-oxidation
ABCA3 protein (ATP-Binding Cassette membra A3):
assist w/ transport of phospholipid into lamella bodies and involved in lamellar body formation
infant with ABCA3 deficiency does not have DPPC and PG, decreased lamella bodies.
AR, most COMMON known genetic cause of surfactant deficiency.
90% surfactant recycled
L/S Ratio
if L/S ratio > 2, lecthin/sphingomyelin ratio
marker of lung maturity
usually around 35 weeks
SP-B deficiency
Autosomal recessive.
Chromosome 2
present with: term RDS, unsustained response to surfactant.
no lamellar bodies, no tubular myelin or surfactant function.
fatal
SP-C deficiency
Autosomal dominant (50% de novo)
gene on chromosome 8.
C: Chronic lung disease of infancy (CPI)
RDS, ARDS, non-specific interstitial lung disease
ILD > RDS
ABCA3 Deficiency
Autosomal Recessive
Chromosome 16
critical for the formation of lamella body.
(can be seen under electromiscoscopy)
RDS > ILD
E/M: Small abnormal vesicles with electron dense inclusions. LB & TM in surfactant layer are absent. Excess LB in type II cells.
lamella body is where surfactant is stored.
Cystic Fibrosis
Autosomal Recessive (1:2500)
immunoreactive trypsinogen
increased Na absorption (dehydration of luminal content in gut)
Can have hypoChloremic metabolic alkalosis
what’s the next stage in management in vocal cord paralysis
MRI to exclude Chiari malformation.
Treatment: conservative
Boyles Law
P1V1 = P2V2
air flow from high pressure to low pressure
P: pressure
V: volume
What determines the type of gas flow (laminar vs. turbulent flow)
Reynolds Number
Laminar flow: molecules travel in straight line
Turbulent: branching airways and large airways. occurs at high rate of gas flow.
total respiratory resistance is the sum of what
Rrs (total respiratory system resistance) = lung tissue resistance (high in neonate, generate during inflation and deflation) + airway resistance (nasal) + chest wall resistance (decreased in premature infants)
Airway is the majority (55%, mostly nasal)
Time constance calculation
(IMPORTANT)
Time constant = resistance x compliance
R = delta P/delta Q
C = delta V/delta P
Time constance = delta V/ delta Q
take 3-5 TC for relatively complete inspiratory or expiratory phase. (or 3x TC to reach 95% equilibrium)
long TC = slow filling/emptying
(i.e. BPD, LGA w. normal lung)
Healthy infant TC = ~ 0.12s.
for RDS = ~ 0.05s.
larger animals has more compliance and higher time constance => larger baby, need longer iTime.
What is anatomic dead space, alveolar dead space, and physiological dead space
Physiological dead space = anatomic + alveolar
Vd/Vt = (PaCO2 - PeCO2) / PaCO2
Bohr equation
Vt = Va + Vd
Vd is dead space volume
Vt is tidal volume
PaCO2 is CO2 in arterial blood
PeCO2 is the partial pressure of CO2 in the expired air
where’s the respiraotry center in brainstem
Medulla and pons
PaCo2 affect what receptors in control of breathing
Central chemoreceptor in medulla oblongata
PcCO2 and H+
and peripheral chemo receptors (carotid and aortic bodies)
PaO2 affect what receptors in control of breathing
peripheral chemoreceptor in carotid and aortic arch
preterm has decreased response to hypoxia.
larger animal and time constant
larger animals has more compliance and higher time constance
TC = R x compliance
3x TC to reach 95% equilibrium.
larger baby, need longer iTime.