A 32-year-old woman undergoes elective cesarean section. On postoperative day 5, the surgical wound shows good epithelialization, early granulation tissue formation, and increased tensile strength. Regarding the molecular and cellular events in her wound at this stage, all of the following are true EXCEPT:

Question

Accepted Answer

D. Neutrophils remain the dominant inflammatory cell and continue to orchestrate tissue remodeling and collagen synthesis. ## Cellular and Molecular Events in the Proliferative Phase (Day 5 Post-Wound)

### Clinical Context
At postoperative day 5, the wound is transitioning from the inflammatory phase into the proliferative phase. Epithelialization is underway, granulation tissue is forming, and tensile strength is beginning to increase.

### Dominant Cell Populations by Phase

| Phase | Timeline | Dominant Cell | Role |
|-------|----------|---------------|------|
| **Inflammatory (early)** | 0–24 hours | Neutrophils | Bacterial killing, debris removal, cytokine release |
| **Inflammatory (late)** | 24–72 hours | Macrophages | Cytokine production, angiogenic factor release, tissue remodeling |
| **Proliferative** | Day 3–5 onwards | Fibroblasts, Myofibroblasts, Endothelial cells | Collagen synthesis, angiogenesis, wound contraction |

**Key Point:** By day 5, the **inflammatory phase is waning**. Neutrophils are being cleared (via apoptosis and phagocytosis by macrophages), and macrophages are transitioning to a reparative phenotype. The proliferative phase is now dominant.

### Why Option 3 Is Incorrect

**High-Yield:** Neutrophils are **NOT** the dominant inflammatory cell at day 5. By this time:
- Neutrophils have largely undergone apoptosis and been cleared
- Macrophages are the predominant inflammatory cell and continue into the proliferative phase
- Fibroblasts, myofibroblasts, and endothelial cells are now the primary drivers of wound healing

Neutrophils peaked at 24–48 hours and are minimal by day 5. The statement that "neutrophils remain the dominant inflammatory cell" is **false**.

### Correct Events at Day 5 (Proliferative Phase)

**Option 1 — TRUE:** Fibroblasts are actively migrating and depositing type III collagen (the predominant collagen in early healing; type I becomes dominant during remodeling).

**Option 2 — TRUE:** Angiogenesis is driven by:
- VEGF (released by macrophages and hypoxic cells)
- HIF-1α (activated by hypoxia in the wound)
- FGF (fibroblast growth factor)
- PDGF (platelet-derived growth factor)

**Option 3 — TRUE:** Myofibroblasts (α-smooth muscle actin–positive fibroblasts) appear by day 3–5 and mediate wound contraction via actin stress fibers. They are derived from resident fibroblasts and bone marrow–derived fibrocytes.

### Clinical Pearl

**Warning:** A common exam trap is confusing the **inflammatory phase** (dominated by neutrophils and macrophages) with the **proliferative phase** (dominated by fibroblasts and myofibroblasts). At day 5, you are well into proliferation; inflammation is receding.

**Mnemonic:** **FAVE** = Fibroblasts, Angiogenesis, VEGF, Epithelialization — the hallmarks of the proliferative phase (days 3–21).

Answer

A. Fibroblasts are actively migrating into the wound and depositing type III collagen as the predominant collagen type

Answer

B. Myofibroblasts derived from fibroblasts are beginning to appear and will contribute to wound contraction

Answer

C. Angiogenesis is occurring via VEGF (vascular endothelial growth factor) signaling and hypoxia-inducible factor (HIF-1α) activation

Explanation

Cellular and Molecular Events in the Proliferative Phase (Day 5 Post-Wound)

Clinical Context

Dominant Cell Populations by Phase

Why Option 3 Is Incorrect

Correct Events at Day 5 (Proliferative Phase)

Clinical Pearl

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Phase	Timeline	Dominant Cell	Role
Inflammatory (early)	0–24 hours	Neutrophils	Bacterial killing, debris removal, cytokine release
Inflammatory (late)	24–72 hours	Macrophages	Cytokine production, angiogenic factor release, tissue remodeling
Proliferative	Day 3–5 onwards	Fibroblasts, Myofibroblasts, Endothelial cells	Collagen synthesis, angiogenesis, wound contraction