Mechanism of PDA closure

**The mechanism of closure of Patent Ductus Arteriosus (PDA) after birth involves 5 steps:**
**Step 1: Increase in Oxygen Levels**
- After birth, lungs expand and oxygen levels in the blood increase.
- Higher oxygen levels signal the ductus arteriosus to close.
**Step 2: Release of Constricting Hormones**
- Increased oxygen triggers release of constricting hormones like:
 - **Bradykinin degradation increases** (bradykinin normally keeps PDA open, so its decrease helps closure)
 - Endothelin-1 increases (constricts ductus arteriosus)
 - Prostaglandin F2α increases (constricts ductus arteriosus)
**Step 3: Decrease in Dilating Prostaglandins**
- Decrease in prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) levels:
 - These prostaglandins normally keep the ductus arteriosus open during fetal life.
**Step 4: Muscular Contraction**
- The ductus arteriosus muscle layer contracts due to the hormonal changes.
- This contraction reduces blood flow through the ductus arteriosus.
**Step 5: Endothelial Cell Overgrowth and Fibrosis**
- Within 1-4 weeks after birth, endothelial cells overgrow the ductus arteriosus opening.
- Fibrosis (scar tissue formation) permanently closes the ductus arteriosus.



**Mechanisms of PDA closure fail in preterm babies due to several reasons:**
1. **Immature Lung Function**: 
 - Lower oxygen levels in blood due to inadequate lung expansion and gas exchange.
 - Delays the trigger for PDA closure.
2. **Increased Sensitivity to Dilating Prostaglandins**:
 - Preterm babies have higher levels of prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2).
 - These prostaglandins keep the PDA open.
3. **Decreased Sensitivity to Constricting Hormones**:
 - Lower response to endothelin-1 and other constricting hormones.
 - Reduces PDA constriction and closure.
4. **Immature Ductus Arteriosus Muscle**:
 - Weaker muscular contraction of the ductus arteriosus.
 - Fails to reduce blood flow through the PDA effectively.
5. **Genetic and Environmental Factors**:
 - Genetic predisposition.
 - Antenatal exposure to magnesium sulfate or other medications that relax smooth muscles.
6. **Lower Bradykinin Degradation**:
 - Bradykinin levels remain higher, promoting PDA patency.
7. **Increased Inflammatory Mediators**:
 - Elevated levels of inflammatory markers promote PDA dilation.
These factors combined increase the likelihood of persistent patent ductus arteriosus (PDA) in preterm infants.

**Comparison of PDA Closure Duration in Preterm vs Term Babies:**
**Functional Closure:**
- Refers to cessation of significant blood flow through the PDA.
 
| | Preterm Babies | Term Babies |
| --- | --- | --- |
| **Functional Closure Duration** | 7-14 days | 1-3 days |
**Anatomical Closure:**
- Refers to complete physical closure of the PDA duct.
| | Preterm Babies | Term Babies |
| --- | --- | --- |
| **Anatomical Closure Duration** | 4-12 weeks | 1-4 weeks |
In summary:
- Preterm babies take longer to achieve both functional (7-14 days vs 1-3 days) and anatomical closure (4-12 weeks vs 1-4 weeks) of PDA compared to term babies.
- This prolonged duration increases the risk of complications in preterm infants.



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