cardiorespiratory adaptation at birth Flashcards
1
Q
What are the 5 stages of lung development?
A
- Fairly predictable in time scale
- Embryonic - lung buds start to develop. Respiratory diverticulum comes off of the esophageal ridge - An outpouching of the fore gut that will become the respiratory tract. Bifurcation into left and right
- Pseudoglandular - multiple levels of branching, all airways are still closed (no lumen)
- Canalicular - start to get holes and have open tubes. Start to see little alveol, but v small numbers. Develop terminal bronchioles
- Saccular - more and more complex. Get surfactant formation about 24 weeks
- Alveolar - sustainable airways ready for birth
2
Q
What growth factors are required?
A
- FOXA2 - branching
- FGF-10, SHH, BMP4 - outgrowth of new buds
- Gli proteins - branching
- VEGF - angiogenesis
3
Q
What are the time frames for alveolar development?
A
- 24 weeks, saccules develop - VEGF causes capillaries to develop around each
- 32 weeks, shallow indentations
- Most development post term - mainly by growth in number. Adult numbers of alveoli by 4 years, also grow in size with age
- Pneumocytes - type 1 and 2 present after 22 weeks. From 24 weeks lamellar bodies present (store surfactant)
4
Q
What can cause structural pathologies?
A
- Extrinsic restriction - congenital diaphragmatic hernia, effusions, thoracic or vertebral abnormalities
- Intrinsic restriction - lung cysts (cystic adenomatoid malformation)
- Malnutrition (vit A)
- Smoking
- Time of onset - <16 weeks, branching is irreversibly affected, potentially permanent reduction in alveolar number. >16 weeks, predominant alveolar numbers
5
Q
What is lung liquid?
A
- Foetal lungs are filled with liquid
- 4-6mls/kg midgestation -> 20mls/kg term
- Similar cations to plasma, with higher Cl- but much lower protein and bicarbonate
- Composes some of amniotic fluid, however most is urine
6
Q
How is lung fluid secreted?
A
- Secondary active transport of Cl from interstitium to lumen - the Cl will move first, pulling Na and water with it
- Get a very slight positive pressure in the lungs because of its production
- Lung fluid is required for lung growth, but not branching
7
Q
How is lung fluid absorbed?
A
- Active sodium transport in apical membranes
- Don’t want lungs full of liquid after delivery
- Some comes out through coughing, but the adrenaline release of your birth itself will turn off lung fluid secretion
- Thyroid hormone and cortisol are required for maturation of the foetal lung response to adrenaline
- Exposure to postnatal oxygen increases sodium transport across pulmonary epithelium
8
Q
What may cause lung liquid pathologies?
A
- Oligohydramnios
- Foetal breathing abnormalities
- Delivery without labour
9
Q
What is oligohydramnios?
A
- Dont have enough fluid surrounding the foetus - leak or not enough produced
- Kidneys dont work so cant produce urine
- Lungs dont work properly
- Usually die first due to lungs
10
Q
What causes some foetal breathing difficulties?
A
- Neuromuscular disorders
- Phrenic nerve agenesis
- Congenital diaphragmatic hernia
- Foetal breathing slows lung liquid loss - maintains expansion
11
Q
Why might there be lung liquid pathology from delivery without labour?
A
- Can get transient tachypnoea newborn (TTN) from c-section
- Baby wont have surge in cortisol and adrenaline like in natural childbirth
12
Q
How is surfactant produced and degraded?
A
- Produced by type 2 pneumocytes
- Stored in lamellar bodies
- Degraded in alveoli - absorbed and recycled by alveolar cells. 10 hr turnover time
- Negative feedback system to regulate release - also stretch receptors (b-adrenergic_
13
Q
What is surfactant?
A
- Mix of phospholipids, neutral lipids and protein
- Phosphatidylcholine = 80%, P-glycerol = 10%
- 60% PC desaturated, predominantly palmitic acid
- So dipalmitoyl PC is the major component
14
Q
Why do we have surfactant?
A
- Prevents atelectasis - reduces work to breathe
- Achieved by reduced surface tension
- Solid at body temp; stabilises alveoli. Can phase shift between liquid gel and solid very quickly
- When alveoli are open, very low internal pressure, lower ST, but gaps between PL molecules in surfactant
- Areas exposed to water will be pulled on to try and close it.
- AS it shrinks down, molecules become compressed, eventually like a solid
15
Q
What are the 4 types of proteins in Surfactant?
A
SP-A,B,C,D
16
Q
What is SP-A?
A
- Large glycoprotein
- Gene on chr10, only expressed in lung
- Increased production after 28 weeks
- Essential in determining structure of tubular myelin; stability and spreading of PLs; negative feedback loop
17
Q
What is SP-B?
A
- 1-2% of surfactant by weight
- Gene on Chr2
- Glucocorticoids increase expression
- required for tubular myelin and spreading
- In vivo has greatest activity in terms of lung compliance
- Protects surfactant film from inactivation and degradation by serum proteins
18
Q
What is SP-C?
A
- Gene on Chr 8
- 35AA long - smaller
- Significantly enhances absorption and spreading on PLs
19
Q
What is SP-D?
A
- MW 46000
- Increases expression with gestation
- Expression is widely distributed in epithelial cells
- No significant surfactant activity
- Immune function
20
Q
What are 3 things that affect surfactant production?
A
- Glucocorticoids
- Thyroid hormones
- Insulin
21
Q
How do glucocorticoids affect surfactant production?
A
- Increased production at end of gestation - increases DPPC
- Dexamethasone increases b2-adrenoceptor gene expression -> increased surfactant secretion
22
Q
How do Thyroid hormones affect surfactant production?
A
- T4 increases production of surfactant
- T3 crosses placenta
- TRH increases PL independent of T3/4
23
Q
How does insulin affect surfactant?
A
- Delays maturation of type 2 cells, decreases % saturated PC
- Delayed PG (phosphatidylglycerol)
- Increased sugar levels delay lung maturation
24
Q
What surfactant pathologies are there?
A
- In prematurity - PC relatively unsaturated (unstable monolayer buckles on expiration); PG replaces PI with increased gestation; leaky capillary membranes > fibrin deosition, inhibits reduction of ST
- SP deficiencies - SP-B absence leads to reduced PG; no secretion of normal surfactant and so lethal
- SP-C -> interstitial lung disease
25
Q
What happens to the lungs at birth?
A
- Lung liquid production ceases during labour
- Foetal breathing ceases
- Cooling stimulates breath along with other senses
- Air replaces fluid in minutes
- Some squeezed out, most absorbed into lymphatics and capillaries
- Rapid fall in airway resistance, increases FRC
- Slower increase in compliance over 24 hrs
26
Q
What is the regulation of breathing?
A
- Normal rhythm - inspiration (inspiratory muscle contraction), Passive with a bit of active expiration
- Generated in respiratory centre in ventrolateral brainstem
27
Q
How is the breathing controlled?
A
- Foetus tries to stop all nonessential activity if hypoxic
- Hypoxic gas mixture will cause breathing rates and effort to go up in children
- Term babies will revert to more intermittent breathing patterns
- preterm babies it is much more marked - may even do it at low altitude - may not restart
28
Q
How does prematurity affect breathing/lungs?
A
- Respiratory centres less well developed
- Very immature neonate responds lika a foetus - apnoea
- Cold babies dont have initial hyperventilation
- Sometimes, premature babies just stop breathing
- Caffiene is a respiratory stimulant - iv caffiene reduces apnoeic prematurity
29
Q
What neurological adaptations are there?
A
- Built to withstand labour - fewer synapses and reduced O2 requirement. Newborn babies utilise non-oxidative glycolysis and ketone bodies
- Hypoxia leads to redirection of blood flow in foetus - will send blood to brain, heart and adrenals, turn off blood supply to nonessential areas like gut
