Cardiorespiratory Adaptation At Birth I Flashcards
What are the 5 stages of lung development?
- Embryonic
- Pseudoglandular
- Canalicular
- Saccular
- Alveolar
Describe the embryonic phase
- @ 3-6 weeks
- Respiratory diverticulum develops off esophagotracheal ridge
- Lung bud develops from foregut
- This all turns into resp tract
- Trachea develops with its 2 lung buds as bifurcation occurs
- Further development of airways -> next stage
Describe the pseudoglandular phase
- @ 6-17 weeks
- Branching in lungs to form terminal bronchioles
- Airways still closed however as no lumen
- No respiratory bronchioles, no alveoli present (yet)
Describe the canalicular phase
- @ 17-26 weeks
- Each terminal bronchiole divides into 2+ respiratory bronchioles
- “Canunlate” - open holes, to breathe through, tubes
Describe the saccular phase
- @ 27 weeks -> term
- Respiratory bronchioles divide into 2-3 alveolar ducts
- These develop terminal sacs
- Capillaries establish close association
Describe the alveolar phase
- From term -> childhood
- Mature alveoli w/ well-developed epithelial-endothelial association
Which growth factors are involved in lung development?
- Hepatocyte nuclear factor 3beta - foregut
- FGF-10, Sonic hedgehog, BMP4 - outgrowth of new end buds
- Gli proteins - branching
- Vascular endothelial growth factor (VEGF) - angiogenesis
When do the saccules start to develop?
Around 24 weeks
What develops around each saccule and what causes this?
Capillaries - caused by VEGF
Most alvolar development occurs post-term. By what age will there be adult numbers of alveoli?
- 4 years
- Mainly by growth in number
When are pneumocytes present?
- Type 1 and type 2
- Present at 22 weeks
What do lamellar bodies do and when are they present from?
- From 24 weeks
- Store surfactant
In terms of structural pathology, how does the time of onset impact alveoli?
- < 16 weeks, branching irreversibly affected, potentially permanent reduction in number of alveoli
- > 16 weks, branching complete, predominantly alveolar numbers affected
Give examples causing extrinsic restriction in terms of lung development
- Congenital diaphgragmatic hernia
- Effusions
- Thoracic or vertebral abnormalities
Give an example causing intrinsic restriction of lung development
- Lung cysts (cystic adenomatoid malformation)
Apart from time of onset and restriction, what other (lifestyle) factors affect lung development?
- Malnutrition (vit A)
- Smoking
Affect peak flow, alveolar number + lung size
Fetal lungs are filled with liquid, what is the content of lung liquid?
- High sodium (150)
- High chloride (157)
- Low potassium (6.3)
- Low bicarbonate (2.8)
- Low protein (0.03)
Describe lung liquid secretion
- Secondary active transport of Cl from interstitium to lumen
- Sodium and water follow
- Liquid production allows for positive pressure of 1cmH2O
Why is lung fluid required?
- For lung growth
- Not for branching
- Interruption of lung liquid secretion -> abn dpmt
How is lung liquid absorbed?
- Active sodium transport in apical membranes
- Labour & delivery: adrenaline release -> reduced secretion + resorption begins
- Thyroid hormone + cortisol required for maturation of fetal lung response to adrenaline
- Exposure to postnatal oxygen increases sodium transport across pulmonary epithelium
How does oligohydramnios result in abnormal lung development?
- Reduced amniotic fluid surrounding fetus
- Kidney abnormalities + early rupture
- Abnormally developed lungs - die from lung problems
Fetal breathing slows liquid loss - maintains expansion. What conditions can result in fetal breathing abnormalities?
- Neuromuscular disorders
- Phrenic nerve agenesis
- Congenital diaphragmatic hernia
What is TTN (transient tachypnoea newborn) and how does it come about?
- Newborn presenting with abnormally rapid breathing + resp distress, should settle in 6-12 hours
- Due to lack of lung liquid clearing
- Due to delivery without labour - so by elective caesarean section - lack of adrenaline + cortisol, which is important for lung liquid absorption
Pulmonary surfactant is key to sustaining life post-natally. Where is surfactant produced, stored and degraded?
- Produced by type 2 pneumocytes: surfactant phosphatidylcholine prod in endoplasmic reticulum
- Stored in lamellar bodies
- Absorbed and recycled (>90%) by alveolar cells
- Turnover time 10 hours
How is surfactant release regulated?
- Negative feedback
- Also stretch receptors
- B-adrenergic receptors on type 2 cells - increases w gestation
Why do we need surfactant?
- To prevent atelectasis (alveolar collapse) - reduces work to breathe
- Achieved by reduced surface tension
- Solid at body temp - becomes a solid monolayer, stabilises alveoli
What is Laplace’s equation?
Internal pressure = 2 x surface tension / radius
Theory: 2 balloons, blow one up, easier to blow up as it gets bigger but hard to start.
If you put 2 balloons together, one full and one empty, the almost empty one will empty into the full one as there’s a lower surface tension/resistance than the bigger balloon. As radius gets bigger, the internal pressure drops.
What is surfactant made of and which is the most important part?
- Phospholipids
- Neutral lipids (eg cholesterol)
- Protein
Phospholipids most important
What is the lipid part of surfactant made of?
- Phosphatidylcholine comprises 80%
- Phosphatidylglycerol comprises 10%
- 60% PC disaturated, predominantly palmitic acid
- Therefore dipalmitoyl phosphatidylcholine is the major component of surfactant
- Hydrophillic head + hydrophobic tail
List the composition of surfactant by mol weight (%)
- dipalmitoyl phosphatidylcholine 50%
- unsaturated phosphatidylcholine 17%
- serum proteins 8%
- phosphatidylglycerol 7%
- phosphatidylethanolamine 4%
- surfactant specific proteins 2%
What is the difference between function of PC and PG?
- PC reduces alveolar surface tension
- PG promotes spreading of surfactant throughout lungs
There are 4 types of surfactant proteins (SP A-D). How much of the surfactant do they make up by weight?
5-10%
What is SP-A and why is it important?
- Large glycoprotein
- Gene on chromosome 10, only expressed in lung
- Inc prod after 28 weeks
- Essential in:
- determining structure of tubular myelin
- stability + spreading of phospholipids
- negative feedback loop for surfactant
- immune function
What is SP-B and why is it important?
- 1-2% of surfactant by weight, largest volume SP
- Gene on chromosome 2
- Glucocorticoids inc expression
- Required for:
- formation of tubular myelin
- spreading
- combined w lipid mixtures - most of surface activity in vitro + inc lung compliance in vivo
- protects surfactant film from inactivation by serum proteins
What is SP-C and why is it important?
- Chromosome 8
- 35 AA
- Significantly enhances adsorption + spreading on phospholipids
What is SP-D and why is it important?
- Mol weight = 46,000
- Inc expression w gestation
- Expression is widely distributed in epithelial cells
- No significant surfactant activity
- Immune function
How do glucocorticoids contribute to surfactant maturation?
- Increased production of glucocorticoids at end of gestation
- Increases DP PC
- Dexamethasone enhances B2-adrenoreceptor gene expression -> leads to increased endogenous surfactant secretion
How do thyroid hormones contribute to surfactant maturation?
- T4 inc surfactant production
- T3 crosses placenta
- TRH increases phospholipid (independent of T3,4)
How does insulin contribute to surfactant maturation?
- Delays maturation of type 2 pneumocytes, decreases % saturated PC
- Delayed PG
- Inc sugar levels delay lung maturation
What is the surfactant pathology of premature babies?
- PC relatively unsaturated - unstable monolayer which buckles on expiration
- PG replaces PI with increased gestation
- Leaky capillary membranes - fibrin deposition in alveolus - inhibits reduction of surface tension - hyaline membranes
What does a deficiency of SP-B lead to?
- Absence leads to markedly reduced PG
- No secretion of normal surfactant
- Lethal ->> lung transplant possible for some
What does a deficiency of SP-C cause?
Interstitial lung disease
What events lead up to stimulate the baby’s first breath during birth?
- Lung liquid prod ceases during labour
- Fetal breathing ceases
- Cooling stimulates breath along w other sense
- Central chemoreceptor detection of hypoxia
- First breath median time = 10 sec
- High inspiratory pressure, active expiration with high pressure
What happens to the lung liquid upon birth, where does it go?
- Air replaces fluid within minutes
- Some squeezed out, most absorbed into lymph + capillaries
- Rapid fall in airway resistance, inc FRC
- Slower inc in compliance ~ over 24 hours
The normal rhythm for breathing is generated in the respiratory centre, where specifically?
Ventrolateral brainstem
What would happen if the following breathed hypoxic gases for 5 mins?
- Term infant
- Older infant
- Adult
Older infant and adult would be fine - their breathing efforts and RR would go up.
Breathing efforts will go up for 2 mins, then drop for term infant. Due to drive for respiration being immature still so breathing efforts decrease.
What is the control of breathing like in preterm infants?
- Resp centre less well developed
- Very immature neonate responds like a fetus - apnoea
- Cold babies don’t have initial hyperventilation
- Sometimes, premies just stop breathing
What happens with the blood flow when hypoxia occurs in the fetus?
- Leads to redirection of blood flow in fetus
- Blood directed to brain, heart + adrenals
- Blood supply directed away from gut + other non-essential areas
