Pulmonology Flashcards
What is the respiratory tract derived from?
Endoderm
Lung forms from ventral bud of the esophagus–> foregut
Branching dependent on the underlying mesodermal mesenchyme
Describe the vascular supply of the pulmonary system
Pulmonary vasculature forms from branches off the 6th aortic arch- supply intrapulmonary structures, regulate gas exchange
Bronchial arterial system comes off the aorta- supplies conducting airways, visceral pleura, connective tissue, pulmonary arteries
Pre-acinar arteries: adjacent to airways up to and including nonrespiratory bronchioles
develop by angiogenesis (formation of new vessels from pre-existing ones), growth corresponds with airway development, complete by ~16 weeks
Intra-acinar arteries: adjacent to respiratory bronchioles and alveolar ducts, develop by vasculogenesis (de novo vessel formation from mesoderm), growth corresponds with alveolar development, birth to 8-10 years
Aveolarization is enhanced by:
VITAMIN A
THYROXINE
Alveolarization delayed by:
Postnatal steroids
supplemental oxygen
nutritional deficienies
mechanical ventilation
insulin
inflammation
Name the developmental stages of the lung and GA of development
- Embronic ~5 weeks
- Pseudoglandular ~15 weeks
- Cannalicular ~25 weeks
- Saccular ~35 weeks
- Alveolar ~36+ weeks
Every Preemie Can Suck Air
Name major developments in each pulmonary developmental stage
Embryonic: lung forms from ventral bud of esophagus, pulmonary vascular development from 6th aortic arch
Pseudoglandular: all large airway bronchi up to terminal bronchi established, begin to produce amniotic fluid, pneumocyte precursors, separation of thorax and peritoneal cavity (7 weeks)
Canalicular: branch out to terminal bronchioles,
type II pneumocytes begin to differentiate to type I, lung is viable! (adult # of airways completed by 24 weeks)
Saccular: sacs form from the terminal bronchioles, last generation of air spaces completed, gas exchange via alveolar-capillary membranes
Aveolar: alveoli form and increase in diameter, microvascular growth and vessel maturation
Describe type I and type II pneumocytes
Type I:
- fried-egg with tight junctions
- 90% of surface
- gas exchange
- derived from type II cells
Type II:
- cuboidal shape
- 10% of surface
- surfactant metabolism and secretion
- progenitor to type I cells
Fetal lung fluid maintained airway volume similar to _____
funtional residual capacity (20-30ml/kg)
near term FLF production rate is low (4-5ml/kg/hr)
Describe fetal lung fluid production during gestation
epithelial cell has ACTIVE chloride secretion into future air spaces–> osmotic gradient–> flow of liquid into fetal lung
Fetal lung fluid production inhibited by epinephrine (naturally increased with stress of delivery) and beta-adrenergic agonists
Describe how fetal lung fluid is absorbed (3 stages)
PRENATAL (35%):
- decreased formation and secretion of FLF
- ENaC absorbs sodium –> fluid to interstitium
- Increased lymphatic oncotic pressure, low fetal alveolar protein–> fluid to pulmonary lymphatics
ACTIVE LABOR (30%):
- vaginal squeeze
- catecholaline surge–> increasing transepithelial Na+ transport
- Higher cortisol and thyroid hormone concentrations–> increased transepithelial Na+ transport
POSTNATAL (35%):
- lung distention leading to increas in transpulmonary presures–> fluid to interstitium
- increased lymphatic oncotic pressure and low fetal alveolar protein –> fluid to pulmonary lymphatics
Most physiologically active component of surfactant
DPPC: dipalmitoyl phosphatidylcholine
50%
Which surfactant proteins are hydrophilic?
A and D
Which surfactant proteins are induced by steroids?
A, B and C
Which surfactant proteins are hydrophobic?
B and C
Which surfactant proteins are critical for surfactant function?
B and C
Which surfacant protein originates from chromosome 10?
A and D
Which surfactant protein originates from ch 8?
C
Which surfactant protein originates from ch 2?
B
Which surfactant proteins participate in host defense?
A and D
What is the function of surfactant protein A?
- Tubulin myelin formation
- host defense
What is the function of surfatant protein B?
- CRITICAL FOR SURFACTANT FUNCTION
- tubular myelin formation
- surface adsorption of phospholipds
severe respriatory failure soon after birth, surfactant administration i
What is the function of surfactant protein C?
- CRITICAL FOR SURFACTANT FUNCTION
- promotes surface adsorption of phospholipids
What is the function of surfactant protein D?
- host defense
- anti-oxidant
- surfactant lipid homeostasis
What is the most common known genetic cause of surfactant deficiency?
ABCA3 deficiency
Autosomal recessive
lack DPPC and PG, decrease laminar bodies
Clinically looks similar to protein B deficiency
Maternal conditions that accelerate lung maturity
Chronic maternal hypertension
Maternal CV disease
Placental infarction
IUGR
Pregnancy-induced hypertension
Prolonged ROM
Incompetent cervixx
Hemoglobinopathies
Chorioamnionitis (Incr risk for CLD)
Maternal conditions that delay lung maturation
Diabetes
Rh isoimmunization with hydrops
2nd born twin
Male sex
CS
Prematurity
Substances that accelerate lung maturation
Corticosteroids
Thyroid hormones
TSH/TRH
Cyclic adenosine monophosphate
Methylxanthines (caffeine)
Beta-agonists
Prolactin
Estrogens
Epidermal growth factor
Transforming growth factor alpha
Substances that delay lung maturation
Insulin
Transforming growth factor-beta
Androgens
Substances that inactivate surfactant
Meconium
Proteinaceous alveolar edema fluid
What can increase surfactant secretion?
Purines
Prostaglandin
Beta-agonists
Lung distention
What increases flow of fetal lung fluid?
Prostaglandin
Beta-agonists
Fetal breathing
LaPlace’s Law
P= 2T/r
r = radius
T= tension
Which surfactant protein is not present in natural surfactant produced from bovine or porcine lung?
Surfactant protein A
Histopathologic findings in new BPD
- increased alveolar (saccular) diameters
- fewer alveoli (saccules)
- disruption of the collagen network around the saccules
- localization of elastin that is absent from sites of future secondary septation
- BOTH increased and decreased platelet/endothelial cell adhesion molecule (PECAM) staining
Name the most common organisms associated with chorioamnionitis
- Ureaplasma species
- Mycoplasma species
What perfusion zone does the lung normally function in?
Zone III: Pa>Pv>PA
Air trapping and alveolar distention: Zone I and II
Increased extravascular fluid: Zone IV
What are the effects of steroids on the postnatal lung?
Arrest alveolar septation and microvascular development
What are the effects of prenatal steroids on the fetal lung?
mature the fetal lung- decreasing the amount of mesenchymal tissue and increasing potential airspace volume–> arrest of alveolar (saccular) septation
Describe “new BPD”
ALTERED lung development
1. Radiographic findings: hazy lung fields, hyperinflation, minimal cystic emphysema
2. an oxygen or ventilator requirement
3. less airway reactivity compared with infants with classical BPD
4. less pulmonary hypertension (fewer cyanotic spells) compared with infants with classical BPD
5. minimal fibrosis
decreased alveolar septation and microvascular development
Old BPD- direct injury to the lungs
Name variables which contribute to exogenous surfactant distribution in the lungs:
- surface activity- adsorption and spreading
- gravity
- volume- higher volumes = better distribution
- rate of administration- faster = better distribution
- ventilator settings- pressure and PEEP help distribute by clearing fluid from airways
- fluid volume in lungs- high volumes of FLF or edema fluid can result in better distribution
Infant with more advanced gestational age may respond more favorably to surfactant administration
Improved outcomes with surfactant after exposure to antenatal steroids
How does caffeine improve apnea of prematurity?
- Decreases hypoxic depression of breathing
- Decreases periodic breathing
- Improves carbon dioxide sensitivity (shifts curve to the left)
- Increases diaphragmatic activity
- Increases minute ventilation
Central chemoreceptors in the medulla
Increase in H+ (most sensitive)
Increase in paCO2
Peripheral chemoreceptors (carotid and aortic bodies)
Decrease in paO2 (most sensitive)
Increase in paCO2, H+
What components contribute to total respiratory system resistance?
chest wall resistance = 25%
airway resistance = 55%
lung tissue resistance = 20%
Neonate: 50% of AIRWAY resistance is attributable to nasal resistance
Airway resistance decreases during inspiration
Airway resistance increases during expiration
Resistance of both laminar and turbulent flwow increases with increased length of airway and decreases with increasing radius
Formula used in neonate with chylothorax
Medium chain triglyceride formula
Characteristics of fluid from chylothorax
Xanthochromic
Lymphocytic predominance
Elevated protein count
High triglyceride level
Most common site where the thoracic duct drains lymph into the venous system:
IJ into subclavian
Immunologic pulmonary defense mechanisms
Innate and nonspecific (neonate relies on these more):
1. macrophages- primary effector cells of innate immunity, important for phagocytosis, microbial killing, local immune modulation, antigen presentation, recongizing pathogen-associated molecular patterns; dont work as well as adult macrophages, impaired response to pro-inflammatory mediators (ex interferon gamma)- impedes recruitemnt of other inflam cels
2. cytokines- amplify inflammatory respone and recruit lymphocytes/dendritic cells to commence an adaptive response
3. chemotaxins
4. granulocytes
5. NK cells
Adaptive and specific (immunologic memory and long-term cell-mediated and humoral immune systems- immature in newborn)
1. antigen-presenting cells
2. T cells
3. B cells
4. immunoglobulins
Mechanical pulmonary defense mechanisms
Larynx and pharynx
Mucus
Mucociliary clearance mechanisms: cough reflex
Filter 99% of inhales particles and microorganisms–> reduce antigen exposure/activation of host immune responses
How do polymorphonuclear leukocytes help immune defense in the lungs?
Recruitable phagocytes, rapidly mobilized
Reservoir: pulmonary circulation
Do not function as well as adult PMNs- increase risk of infection in newborns vs adults
Dendritic cells immune function in the lungs
present antigen to lymphocytes during adaptive immune response
Less efficient at presenting to T-cells
Do not produce interfon gamma as well as adult cells
Delay expansion of memory Tcells
Increase risk fo infection
Endothelial cell immune function in the lung
express MHC class II - antigen presentation (same as dendritic cells)
Produce and secrete cytokines
Express TLRs- adhesiona, chemotaxis, recruitement, activation of inflammatory cells at the “gate” between vascular space and interstitium of lung
Immune function of pulmonary fibroblasts in the lung
produce structural and matrix proteins
respond to macrophage-derived TNF and interleukin-1–> secrete cytokines–> amplify local immune response
Pathophysiologic events following meconium aspiration
- Ball-valve effect: over-distention, pneumothorax, gas trapping, decreased compliance
- Surfactant dysfunction
- Pulmonary hypertension
- Airway epithelial cell necrosis- respond to meconium by swelling, rounding, and sloughing into the airways
How does CPAP prevent bradycardia event?
Primary pulmonary hypoplasia
Mostly unilateral although can be bilateral- affects both lungs with equal frequency
Present asymptomatic or severe respiratory distress
Can also have congenital anomalies of the tracheobronchial tree, CV system, vertebrae
Small ipsilateral pulmonary artery and hypoplasia/absence of ipsilateral bronchus
CXR: variable degrees of underdevelopment of lung, assymetry of the thorax
Beaking in a pressure/volume loop
overdistention
Normal pressure/volume loop
P/V loop with decreased compliance
Curve shifts to the right
Air trapping
Air trapping on flow/volume loop
Flow volume loops
BPD pressure/volume loop
BPD flow/volume loop
Nitric oxide works in the lung
How do mechanical defense mechanisms in the lunc increase risk for neonatal infeciton?
- nasal hairs and turbinates cause turbulent flow in the upper airway –> incr contact and deposition of particles on epithelial mucus layer
- Airway bifurcations induce gas flow turbulence–> enhance deposition of particles
- mucociliary function and airway reflexes are immature in first few weeks after birth
- airway epithelium distrupted by mechanical devices (ETT, suction catheters, feeding tubes)–> increased risk for bacterial infection
Factors affecting alveolarization
Part of the renin-angiotensin system that is most active in the lung
Angiotensin converting enzyme
Ways that RDS and BPD are similar and different
Similar:
1. Increases in BNP
2. Increased intrapulmonary shunting
3. Increased pulmonary artery pressure
4. Increased RV dilation
Different: RDS causes increased CONSTRICTION of extra-alveolar vessels, BPD causes increased DILATION of extra-alveolar vessels
RDS pressure volume loop
needing increased initial pressure to open lungs
Early onset GBS sepsis can be a factor in later diagnosis of:
R sided CDH
Genetic defect in congenital central hypoventilation syndrom
PHOX2B
Compliance
A-a gradient
altitude questions
oxygen carrying capacity
mean airway pressure
what neurotransmitter is implicated in SIDS?
serotonin
when in utero does the fetus breath?
REM sleep
Antenatal Late Preterm Steroids
ALPS trial
2016
significant decrease in composite outcome of need for respiratory support in first 3 days of life
no difference in rates of admission to NICU, incidence of RDS, need for mechanical ventilation
INCREASE in incidence of HYPOGLYCEMIA
how to corticosteroids reduce inflammation?
suppress transcription of mRNAs that code for proinflammatory proteins
promote transcription of mRNAs that code for anti-inflammatory proteins
binds to specific intracellular glucocorticoid receptor –> creates complex –> translocation into the nucleus
suppress expression of phospholipase A2, COX1, COX2 indirectly through synthesis of annexin A1
most commonly noted long term sequelae of CDH
GE reflux
