Cardiorespiratory Adaptation At Birth I Flashcards
(48 cards)
1
Q
What are the 5 stages of lung development?
A
- Embryonic
- Pseudoglandular
- Canalicular
- Saccular
- Alveolar
2
Q
Describe the embryonic phase
A
- @ 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
3
Q
Describe the pseudoglandular phase
A
- @ 6-17 weeks
- Branching in lungs to form terminal bronchioles
- Airways still closed however as no lumen
- No respiratory bronchioles, no alveoli present (yet)
4
Q
Describe the canalicular phase
A
- @ 17-26 weeks
- Each terminal bronchiole divides into 2+ respiratory bronchioles
- “Canunlate” - open holes, to breathe through, tubes
5
Q
Describe the saccular phase
A
- @ 27 weeks -> term
- Respiratory bronchioles divide into 2-3 alveolar ducts
- These develop terminal sacs
- Capillaries establish close association
6
Q
Describe the alveolar phase
A
- From term -> childhood
- Mature alveoli w/ well-developed epithelial-endothelial association
7
Q
Which growth factors are involved in lung development?
A
- Hepatocyte nuclear factor 3beta - foregut
- FGF-10, Sonic hedgehog, BMP4 - outgrowth of new end buds
- Gli proteins - branching
- Vascular endothelial growth factor (VEGF) - angiogenesis
8
Q
When do the saccules start to develop?
A
Around 24 weeks
9
Q
What develops around each saccule and what causes this?
A
Capillaries - caused by VEGF
10
Q
Most alvolar development occurs post-term. By what age will there be adult numbers of alveoli?
A
- 4 years
- Mainly by growth in number
11
Q
When are pneumocytes present?
A
- Type 1 and type 2
- Present at 22 weeks
12
Q
What do lamellar bodies do and when are they present from?
A
- From 24 weeks
- Store surfactant
13
Q
In terms of structural pathology, how does the time of onset impact alveoli?
A
- < 16 weeks, branching irreversibly affected, potentially permanent reduction in number of alveoli
- > 16 weks, branching complete, predominantly alveolar numbers affected
14
Q
Give examples causing extrinsic restriction in terms of lung development
A
- Congenital diaphgragmatic hernia
- Effusions
- Thoracic or vertebral abnormalities
15
Q
Give an example causing intrinsic restriction of lung development
A
- Lung cysts (cystic adenomatoid malformation)
16
Q
Apart from time of onset and restriction, what other (lifestyle) factors affect lung development?
A
- Malnutrition (vit A)
- Smoking
Affect peak flow, alveolar number + lung size
17
Q
Fetal lungs are filled with liquid, what is the content of lung liquid?
A
- High sodium (150)
- High chloride (157)
- Low potassium (6.3)
- Low bicarbonate (2.8)
- Low protein (0.03)
18
Q
Describe lung liquid secretion
A
- Secondary active transport of Cl from interstitium to lumen
- Sodium and water follow
- Liquid production allows for positive pressure of 1cmH2O
19
Q
Why is lung fluid required?
A
- For lung growth
- Not for branching
- Interruption of lung liquid secretion -> abn dpmt
20
Q
How is lung liquid absorbed?
A
- 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
21
Q
How does oligohydramnios result in abnormal lung development?
A
- Reduced amniotic fluid surrounding fetus
- Kidney abnormalities + early rupture
- Abnormally developed lungs - die from lung problems
22
Q
Fetal breathing slows liquid loss - maintains expansion. What conditions can result in fetal breathing abnormalities?
A
- Neuromuscular disorders
- Phrenic nerve agenesis
- Congenital diaphragmatic hernia
23
Q
What is TTN (transient tachypnoea newborn) and how does it come about?
A
- 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
24
Q
Pulmonary surfactant is key to sustaining life post-natally. Where is surfactant produced, stored and degraded?
A
- 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
25
How is surfactant release regulated?
* Negative feedback
* Also stretch receptors
* B-adrenergic receptors on type 2 cells - increases w gestation
26
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
27
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.
28
What is surfactant made of and which is the most important part?
* Phospholipids
* Neutral lipids (eg cholesterol)
* Protein
Phospholipids most important
29
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
30
List the composition of surfactant by mol weight (%)
1. dipalmitoyl phosphatidylcholine 50%
2. unsaturated phosphatidylcholine 17%
3. serum proteins 8%
4. phosphatidylglycerol 7%
5. phosphatidylethanolamine 4%
6. surfactant specific proteins 2%
31
What is the difference between function of PC and PG?
* PC reduces alveolar surface tension
* PG promotes spreading of surfactant throughout lungs
32
There are 4 types of surfactant proteins (SP A-D). How much of the surfactant do they make up by weight?
5-10%
33
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
34
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
35
What is SP-C and why is it important?
* Chromosome 8
* 35 AA
* Significantly enhances adsorption + spreading on phospholipids
36
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
37
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
38
How do thyroid hormones contribute to surfactant maturation?
* T4 inc surfactant production
* T3 crosses placenta
* TRH increases phospholipid (independent of T3,4)
39
How does insulin contribute to surfactant maturation?
* **Delays maturation** of type 2 pneumocytes, decreases % saturated PC
* Delayed PG
* Inc sugar levels delay lung maturation
40
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
41
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
42
What does a deficiency of SP-C cause?
Interstitial lung disease
43
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
44
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
45
The normal rhythm for breathing is generated in the respiratory centre, where specifically?
Ventrolateral brainstem
46
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.
47
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
48
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
